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  • 1.
    Abraham, Sheela Ann
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Edwards, Katarina
    Karlsson, Göran
    MacIntosh, Scott
    Mayer, Lawrence D.
    McKenzie, Cheryl
    Bally, Marcel B.
    Formation of transition metal-doxorubicin complexes inside liposomes2002In: Biochimia et Biophysica Acta, Vol. 1565, p. 41-54Article in journal (Refereed)
  • 2. Abrahama, Sheela A
    et al.
    Edwards, Katarina
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical Chemistry. Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Karlsson, Göran
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical Chemistry. Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Hudona, Norma
    Mayera, Lawrence D.
    Bally, Marcel B.
    An evaluation of transmembrane ion gradient-mediated encapsulation of topotecan within liposomes2004In: Journal of Controlled Release, Vol. 96, no 3, p. 449-461Article in journal (Refereed)
  • 3.
    Agmo Hernández, Víctor
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Eriksson, Emma K.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ubiquinone-10 alters mechanical properties and increases stability of phospholipid membranes2015In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1848, no 10, p. 2233-2243Article in journal (Refereed)
    Abstract [en]

    Abstract Ubiquinone-10 is mostly known for its role as an electron and proton carrier in aerobic cellular respiration and its function as a powerful antioxidant. Accumulating evidence suggest, however, that this well studied membrane component could have several other important functions in living cells. The current study reports on a previously undocumented ability of ubiquinone-10 to modulate the mechanical strength and permeability of lipid membranes. Investigations of DPH fluorescence anisotropy, spontaneous and surfactant induced leakage of carboxyfluorescein, and interactions with hydrophobic and hydrophilic surfaces were used to probe the effects caused by inclusion of ubiquinone-10 in the membrane of phospholipid liposomes. The results show that ubiquinone in concentrations as low as 2 mol.% increases the lipid packing order and condenses the membrane. The altered physicochemical properties result in a slower rate of release of hydrophilic components, and render the membrane more resistant towards rupture. As judged from comparative experiments using the polyisoprenoid alcohol solanesol, the quinone moiety is essential for the membrane stabilizing effects to occur. Our findings imply that the influence of ubiquinone-10 on the permeability and mechanical properties of phospholipid membranes is similar to that of cholesterol. The reported data indicate, however, that the molecular mechanisms are different in the two cases.

  • 4.
    Agmo Hernández, Víctor
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Karlsson, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Intrinsic Heterogeneity in Liposome Suspensions Caused by the Dynamic Spontaneous Formation of Hydrophobic Active Sites in Lipid Membranes2011In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 27, no 8, p. 4873-4883Article in journal (Refereed)
    Abstract [en]

    The spontaneous, dynamic formation of hydrophobic active sites in lipid bilayer membranes is studied and characterized. It is shown that the rates of formation and consumption of these active sites control at least two important properties of liposomes: their affinity for hydrophobic surfaces and the rate by which they spontaneously release encapsulated molecules. The adhesion and spreading of liposomes onto hydrophobic polystyrene nanoparticles and the spontaneous leakage of an encapsulated fluorescent dye were monitored for different liposome compositions employing Cryo-TEM, DLS, and fluorescence measurements. It was observed that an apparently homogeneous, monodisperse liposome suspension behaves as if composed by two different populations: a fast leaking population that presents affinity for the hydrophobic substrate employed, and a slow leaking population that does not attach immediately to it. The results reported here suggest that the proportion of liposomes in each population changes over time until a dynamic equilibrium is reached. It is shown that this phenomenom can lead to irreproducibility in, for example, spontaneous leakage experiments, as extruded liposomes leak much faster just after preparation than 24 h afterward. Our findings account for discrepancies in several experimental results reported in the literature. To our knowledge, this is the first systematic study addressing the issue of an existing intrinsic heterogeneity of liposome suspensions.

  • 5.
    Agmo Hernández, Víctor
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Reijmar, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Label-Free Characterization of Peptide-Lipid Interactions Using Immobilized Lipodisks2013In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 85, no 15, p. 7377-7384Article in journal (Refereed)
    Abstract [en]

    Lipodisks, planar lipid bilayer structures stabilized by PEG-ylated lipids, were in the present study covalently bound and immobilized onto sensors for quartz crystal microbalance with dissipation monitoring (QCM-D) studies. It is shown that the modified sensors can be used to characterize the interaction of lipodisks with α-helical amphiphilic peptides with an accuracy similar to that obtained with well established fluorimetric approximations. The method presented has the great advantage that it can be used with peptides in their native form even if no fluorescent residues are present. The potential of the method is illustrated by determining the parameters describing the association of melittin, mastoparan X, and mastoparan with immobilized lipodisks. Both thermodynamic and kinetic analyses are possible. The presented method constitutes a useful tool for fundamental studies of peptide–membrane interactions and can also be applied to optimize the design of lipodisks, for example, for sustained release of antimicrobial peptides in therapeutic applications.

  • 6.
    Ahlgren, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Fondell, Amelie
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science. Swedish Radiat Safety Author, Res Unit, Solna Strandvag 96, SE-17116 Stockholm, Sweden.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    EGF-targeting lipodisks for specific delivery of poorly water-soluble anticancer agents to tumour cells2017In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 7, no 36, p. 22178-22186Article in journal (Refereed)
    Abstract [en]

    Concerns regarding poor aqueous solubility, high toxicity and lack of specificity impede the translation of many hydrophobic anticancer agents into safe and effective anticancer drugs. The application of colloidal drug delivery systems, and in particular the use of lipid-based nanocarriers, has been identified as a promising means to overcome these issues. PEG-stabilized lipid nanodisks (lipodisks) have lately emerged as a novel type of biocompatible, nontoxic and adaptable drug nanocarrier. In this study we have explored the potential of lipodisks as a platform for formulation and tumour targeted delivery of hydrophobic anticancer agents. Using curcumin as a model compound, we show that lipodisks can be loaded with substantial amounts of hydrophobic drugs (curcumin/lipid molar ratio 0.15). We demonstrate moreover that by deliberate choice of preparation protocols the lipodisks can be provided with relevant amounts of targeting proteins, such as epidermal growth factor (EGF). Data from in vitro cell studies verify that such EGF-decorated curcumin-loaded lipodisks are capable of EGF-receptor specific targeting of human A-431 tumour cells, and strongly suggest that the interaction between the lipodisks and the tumour cells results in receptor-mediated internalization of the disks and their cargo.

  • 7. Ahlgren, Sara
    et al.
    Reijmar, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    EGF-targeting lipodisks for specific delivery of cationic amphiphilic peptides to tumour cellsManuscript (preprint) (Other academic)
  • 8.
    Ahlgren, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Reijmar, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Targeting lipodisks enable selective delivery of anticancer peptides to tumor cells2017In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 13, no 7, p. 2325-2328Article in journal (Refereed)
    Abstract [en]

    Issues concerning non-specificity, degradation and hemolysis severely hamper the development of membranolytic amphiphilic peptides into safe and efficient anticancer agents. To increase the therapeutic potential, we have previously developed a strategy based on formulation of the peptides in biocompatible nanosized lipodisks. Studies using melittin as model peptide show that the proteolytic degradation and hemolytic effect of the peptide are substantially reduced upon loading in lipodisks. Here, we explored the possibilities to increase the specificity and boost the cytotoxicity of melittin to tumor cells by use of targeting lipodisk. We demonstrate that small (~20 nm) EGF-targeted lipodisks can be produced and loaded with substantial amounts of peptide (lipid/peptide molar ratio >7) by means of a simple and straightforward preparation protocol. In vitro cell studies confirm specific binding of the peptide-loaded disks to tumor cells and suggest that cellular internalization of the disks results in a significantly improved cell-killing effect.

  • 9.
    Almgren, M
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Edwards, K
    Karlsson, G
    Cryo transmission electron microscopy of liposomes and related structures2000In: COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, ISSN 0927-7757, Vol. 174, no 1-2, p. 3-21Article in journal (Refereed)
    Abstract [en]

    Cryo-transmission electron microscopy, c-TEM, has during the last 10 years contributed significantly to the understanding of the numerous, and often complex, structures formed by amphiphilic molecules in dilute aqueous solutions. In particular, the method

  • 10.
    Almgren, M
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Gimel, JC
    Wang, K
    Karlsson, G
    Edwards, K
    Brown, W
    Mortensen, K
    SDS micelles at high ionic strength. A light scattering, neutron scattering, fluorescence quenching, and CryoTEM investigation1998In: JOURNAL OF COLLOID AND INTERFACE SCIENCE, ISSN 0021-9797, Vol. 202, no 2, p. 222-231Article in journal (Refereed)
    Abstract [en]

    Sodium dodecyl sulfate (SDS) in 0.8 M NaCl in D2O has been studied by small-angle neutron scattering (SANS), dynamic light scattering (DLS), and time-resolved fluorescence quenching (TRFQ) measurements in the concentration range from 10 to 80 mM and at te

  • 11.
    Almgren, Mats
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Gustafsson, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Cryotransmission electron microscopy of thin vitrified samples.1996In: Current Opinion in Colloid & Interface Science, ISSN 1359-0294, E-ISSN 1879-0399, Vol. 1, no 2, p. 270-278Article in journal (Refereed)
    Abstract [en]

    During the past few years cryotransmission electron microscopy (EM) of vitrified thin samples has gained acceptance as a standard method in the arsenal of the colloid and interface scientist. The seemingly direct visualization of fluid colloidal structures during the use of cryotransmission EM is both convincing and reliable to the scientist who nowadays has an increasing awareness of the limitations and pitfalls of instrumentation. Notable recent observations include branched threadlike micelles, faceted particles (cubosomes) of a dispersed cubic phase and transitions of certain structures from globular micelles via bilayers to reversed structures. These transitions may be caused by changes of compos ition, temperature, pH, or salt concentration.

  • 12.
    Andersson, Mikael
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Hammarström, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Effect of bilayer phase transitions on vesicle structure and its influence on the kinetics of viologen reduction.1995In: Journal of physical chemistry, ISSN 0022-3654, Vol. 99, no 39, p. 14531-14538Article in journal (Other academic)
    Abstract [en]

    Vesicles were prepared from pure phosphatidylcholines (PC), phosphatidic acids (PA), or dioctadecyldimethylamonium bromide (DODAB). The aggregate structure was examined above and below the gel-to-liquid crystalline transition temperature (T-m) by means of cryo-transmission electron microscopy. The redox reaction between a membrane bound viologen and dithionite was studied in the different lipid systems. It was found that the presence of faceted vesicles or open bilayer fragments, below T-m, lead to double-exponential reduction kinetics.

  • 13.
    Ariöz, Candan
    et al.
    The Arrhenius Laboratories for Natural Sciences, Department of Biochemistry and Biophysics, Stockholm University, Sweden.
    Götzke, Hansjörg
    The Arrhenius Laboratories for Natural Sciences, Department of Biochemistry and Biophysics, Stockholm University, Sweden.
    Lindholm, Ljubica
    The Arrhenius Laboratories for Natural Sciences, Department of Biochemistry and Biophysics, Stockholm University, Sweden.
    Eriksson, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Daley, Daniel O.
    The Arrhenius Laboratories for Natural Sciences, Department of Biochemistry and Biophysics, Stockholm University, Sweden.
    Barth, Andreas
    The Arrhenius Laboratories for Natural Sciences, Department of Biochemistry and Biophysics, Stockholm University, Sweden.
    Wieslander, Åke
    The Arrhenius Laboratories for Natural Sciences, Department of Biochemistry and Biophysics, Stockholm University, Sweden.
    Heterologous overexpression of a monotopic glucosyltransferase (MGS) induces fatty acid remodeling in Escherichia coli membranes2014In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1838, no 7, p. 1862-1870Article in journal (Refereed)
    Abstract [en]

    The membrane protein monoglucosyldiacylglycerol synthase (MGS) from Acholeplasma laidlawii is responsible for the creation of intracellularmembraneswhen overexpressed in Escherichia coli (E. coli). The present study investigates time dependent changes in composition and properties of E. coli membranes during 22 h of MGS induction. The lipid/protein ratio increased by 38% in MGS-expressing cells compared to control cells. Time-dependent screening of lipids during this period indicated differences in fatty acid modeling. (1) Unsaturation levels remained constant for MGS cells (~62%) but significantly decreased in control cells (from 61% to 36%). (2) Cyclopropanated fatty acid content was lower in MGS producing cells while control cells had an increased cyclopropanation activity. Among all lipids, phosphatidylethanolamine (PE)was detected to be themost affected species in terms of cyclopropanation. Higher levels of unsaturation, lowered cyclopropanation levels and decreased transcription of the gene for cyclopropane fatty acid synthase (CFA) all indicate the tendency of the MGS protein to force E. coli membranes to alter its usual fatty acid composition.

  • 14.
    Awad, Doaa
    et al.
    Department of Biochemistry, Alexandria University, Egypt AND Department of Chemistry, University of Bremen, Germany AND Jacobs University Bremen, Germany.
    Bartok, Melinda
    Department of Chemistry, University of Bremen, Germany AND Jacobs University Bremen, Germany.
    Mostaghimi, Farzin
    Department of Chemistry, University of Bremen, Germany.
    Schrader, Imke
    Department of Chemistry, University of Bremen, Germany.
    Sudumbrekar, Neeti
    Department of Chemistry, University of Bremen, Germany.
    Schaffran, Tanja
    Department of Chemistry, University of Bremen, Germany.
    Jenne, Carsten
    Fachbereich C–Anorganische Chemie, Bergische Universit!t Wuppertal, Germany.
    Eriksson, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Winterhalter, Mathias
    Jacobs University Bremen, Germany.
    Fritz, Jürgen
    Jacobs University Bremen, Germany.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Gabel, Detlef
    Department of Chemistry, University of Bremen, Germany AND Jacobs University Bremen, Germany.
    Halogenated Dodecaborate Clusters as Agents to Trigger Release of Liposomal Contents2015In: ChemPlusChem, ISSN 2192-6506, Vol. 80, no 4, p. 656-664Article in journal (Refereed)
    Abstract [en]

    Halogenated dodecaborates, and especially dodecaiodododecaborate(2−), are found to trigger effectively the release of the contents of phospholipid liposomes, including liposomes containing distearoylphosphatidylcholine and cholesterol, which are used clinically in cancer therapy. The basis of the release is studied through differential scanning calorimetry, cryo-transmission electron microscopy, and atomic force microscopy. Upon administration at high concentrations, drastic morphological changes are induced by the dodecaborates. Their possible use in triggered release is suggested.

  • 15. Awad, Doaa
    et al.
    Damian, Luminita
    Winterhalter, Mathias
    Karlsson, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Gabel, Detlef
    Interaction of Na2B12H11SH with dimyristoyl phosphatidylcholine liposomes.2009In: Chemistry and Physics of Lipids, ISSN 0009-3084, E-ISSN 1873-2941, Vol. 157, no 2, p. 78-85Article in journal (Refereed)
    Abstract [en]

    Previous investigations have revealed that the boron cluster compound Na2B12H11SH (BSH) is very potent in causing major structural rearrangements of and leakage from phosphatidylcholine liposomes. This somewhat unexpected finding is interesting from a fundamental point of view and may also constitute the basis of future important pharmaceutical/medical applications of BSH. In order to further explore the BSH-lipid interaction, we have studied the effects caused by BSH on dimyristoyl phosphatidylcholine (DMPC) liposomes.

    Cryo-transmission electron microscopy showed that BSH induces aggregation, membrane rupture and increasing wall thickness of the liposomes. Differential scanning calorimetry revealed a BSH dependent shift of the gel to liquid crystalline phase transition temperature of DMPC. The zeta potential of the liposomes decreases with increasing BSH concentrations, and an apparent dissociation constant of 0.23 mM was found.

    BSH caused leakage of liposome-encapsulated carboxyfluorescein; leakage was higher at 23 °C (near the phase transition temperature) than at 15 °C and 37 °C. It induced lipid mixing only at very high concentrations.

  • 16.
    Bakardzhiev, Pavel
    et al.
    Institute of Polymers, Bulgarian Academy of Sciences, 103-A Acad. G. Bonchev St., 1113 Sofia, Bulgaria.
    Momekova, Denitsa
    Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University e Sofia, 2 Dunav St., 1000 Sofia, Bulgaria.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Konstantinov, Spiro
    Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University e Sofia, 2 Dunav St., 1000 Sofia, Bulgaria.
    Rangelov, Stanislav
    Institute of Polymers, Bulgarian Academy of Sciences, 103-A Acad. G. Bonchev St., 1113 Sofia, Bulgaria.
    Novel polyglycidol-lipid conjugates create a stabilizing hydrogen-bonded layer around cholesterol-containing dipalmitoyl phosphatidylcholine liposomes2015In: Journal of Drug Delivery Science and Technology, ISSN 1773-2247, Vol. 29, p. 90-98Article in journal (Refereed)
    Abstract [en]

    Hybrid liposomes resulting from co-assembly of dipalmitoylphosphatidylcholine and polyglycidol-derivatized lipids were prepared. The latter were composed of a lipid-mimetic residue to which a linear polyglycidol chain (degree of polymerization, DP, in the 23–110 range) was conjugated. Formulations with varying copolymer type and content were prepared by film hydration technique followed by extrusion. The hybrid structures were studied by means of dynamic and electrophoretic light scattering, cryogenic transmission electron microscopy, and fluorescence spectroscopy. Cytotoxicity towards OPM-2 (multiple myeloma) and EJ (human urinary bladder carcinoma) cell lines was assessed as well. Predominantly unilamellar liposomes with mean hydrodynamic diameters in the 113–134 nm range and neutral to slightly negative surface potential were prepared. The integrity of liposomes containing copolymers with DP of the polyglycidol chain 23 and 30 was preserved at copolymer contents up to 10 mol%. Bilayer disks were observed at somewhat lower contents of the copolymers of the highest DP of the polyglycidol chain. The hybrid structures were less leaky than the plain liposomes, which was attributed to formation of a strongly hydrogen-bonded polyglycidol layer around the bilayer membrane. They exhibited low toxicological potential, favorable physicochemical characteristics, and ability to act as containers for sustained release.

  • 17.
    Barreleiro, P C A
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Olofsson, G
    Brown, W
    Edwards, K
    Bonassi, N M
    Feitosa, E
    Interaction of Octaethylene Glycol n-Dodecyl Monoether with Dioctadecyldimethylammonium Bromide and Chloride Vesicles2002In: Langmuir, Vol. 18, p. 1024-1029Article in journal (Refereed)
  • 18. Basanez, G
    et al.
    RuizArguello, MB
    Alonso, A
    Goni, FM
    Karlsson, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Morphological changes induced by phospholipase C and by sphingomyelinase on large unilamellar vesicles: a cryo-transmission electron microscopy study of liposome fusion.1997In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 72, no 6, p. 2630-2637Article in journal (Refereed)
    Abstract [en]

    Cryo-transmission electron microscopy has been applied to the study of the changes induced by phospholipase C on large unilamellar vesicles containing phosphatidylcholine, as well as to the action of sphingomyelinase on vesicles containing sphingomyelin. In both cases vesicle aggregation occurs as the earliest detectable phenomenon; later, each system behaves differently. Phospholipase C induces vesicle fusion through an intermediate consisting of aggregated and closely packed vesicles (the ''honeycomb structure'') that finally transforms into large spherical vesicles. The same honeycomb structure is also observed in the absence of enzyme when diacylglycerols are mixed with the other lipids in organic solution, before hydration. In this case the sample then evolves toward a cubic phase. The fact that the same honeycomb intermediate can lead to vesicle fusion (with enzyme-generated diacylglycerol) or to a cubic phase (when diacylglycerol is premixed with the lipids) is taken in support of the hypothesis according to which a highly curved lipid structure (''stalk'') would act as a structural intermediate in membrane fusion, Sphingomyelinase produces complete leakage of vesicle aqueous contents and an increase in size of about one-third of the vesicles. A mechanism of vesicle opening and reassembling is proposed in this case.

  • 19. Bastiat, Guillaume
    et al.
    Oliger, Patrick
    Karlsson, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Lafleur, Michel
    Development of Non-Phospholipid Liposomes Containing a High Cholesterol Concentration2007In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 23, no 14, p. 7695-7699Article in journal (Refereed)
    Abstract [en]

    We present a novel formulation of non-phospholipid liposomes formed from cholesterol and palmitic acid. Despite the fact that these two lipidic species do not form individually fluid bilayers, we show that once mixed together, fluid bilayers can be obtained and, moreover, these can be extruded using classical extrusion processes to form liposomes. The chem. anal. indicates that these liposomes contain 70 mol % cholesterol, a content that is considerably higher that the satn. limit generally reported for phospholipid bilayers. These cholesterol-rich liposomes, formed with mols. that have low toxicity in vivo, display an improved impermeability relative to that of traditional phospholipid liposomes. In addn., because of the presence of palmitic acid, the stability of the liposomes is pH-dependent, and it is possible to trigger the release of encapsulated materials by pH stimuli.

  • 20.
    Bello, Gianluca
    et al.
    Institute of Pharmaceutical Science, King’s College London, London, United Kingdom.
    Eriksson, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Terry, Ann E.
    Rutherford Appleton Laboratory, Harwell, Oxford, United Kingdom.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Lawrence, M. Jayne
    Institute of Pharmaceutical Science, King’s College London, London, United Kingdom.
    Barlow, David J.
    Institute of Pharmaceutical Science, King’s College London, London, United Kingdom.
    Harvey, Richard D
    Institute of Pharmaceutical Science, King’s College London, London, United Kingdom.
    Characterization of the aggregates formed by various bacterial lipopolysaccharides in solution and upon interaction with antimicrobial peptides2015In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 31, no 2, p. 741-751Article in journal (Refereed)
    Abstract [en]

    The biophysical analysis of the aggregates formed by different chemotypes of bacterial lipopolysaccharides (LPS) before and after challenge by two different anti-endotoxic antimicrobial peptides (LL37 and bovine lactoferricin), was performed in order to determine their effect on the morphology of LPS aggregates. Small-angle neutron scattering (SANS) and cryogenic transmission electron microscopy (cryoTEM) were used to examine the structures formed by both smooth and rough LPS chemotypes and the effect of the peptides, by visualization of the aggregates and analysis of the scattering data by means of both mathematical approximations and defined models. The data showed that the structure of LPS determines the morphology of the aggregates and inuences the binding activity of both peptides. The morphologies of the worm-like micellar aggregates formed by the smooth LPS were relatively unaltered by the presence of the peptides due to their pre-existing high degree of positive curvature being little affected by their association with either peptide. On the other hand the aggregates formed by the rough LPS chemotypes, showed marked morphological changes from lamellar structures to ordered micellar networks, induced by the increase in positive curvature engendered upon association with the peptides. The combined use of cryoTEM and SANS proved to be a very useful tool for studying the aggregation properties of LPS in solution at biologically relevant concentrations.

  • 21.
    Bergstrand, Nill
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Arfvidsson, Maria C.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Kim, Jong-Mok
    Thompson, David H.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Interactions between pH-sensitive liposomes and model membranes2003In: Biophysical Chemistry, ISSN 0301-4622, E-ISSN 1873-4200, Vol. 104, no 1, p. 361-379Article in journal (Refereed)
    Abstract [en]

    The structure and dynamics of two different pH-sensitive liposome systems were investigated by means of cryo-transmission electron microscopy and different photophysical techniques. Both systems consisted of dioleoylphosphatidylethanolamine (DOPE) and contained either oleic acid (OA) or a novel acid-labile polyethylene glycol-conjugated lipid (DHCho-MPEG5000) as stabiliser. Proton induced leakage, lipid mixing and structural changes were studied in the absence and presence of EPC liposomes, as well as in the presence of liposomes designed to model the endosome membrane. Neither DHCho-MPEG5000- nor OA-stabilised liposomes showed any tendency for fusion with pure EPC liposomes or endosome-like liposomes composed of EPC/DOPE/SM/Cho (40/20/6/34 mol.%). Our investigations showed, however, that incorporation of lipids from the pH-sensitive liposomes into the endosome membrane may lead to increased permeability and formation of non-lamellar structures. Taken together the results suggest that the observed ability of DOPE-containing liposomes to mediate cytoplasmic delivery of hydrophilic molecules cannot be explained by a mechanism based on a direct, and non-leaky, fusion between the liposome and endosome membranes. A mechanism involving destabilisation of the endosome membrane due to incorporation of DOPE, seems more plausible.

  • 22.
    Bergstrand, Nill
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Arfvidsson, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Kim, Jon-mok
    Thompson, David H
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Interaction between pH-sensitive liposomes and model membranes2003In: Biophysical Chemistry, ISSN 0301-4622, E-ISSN 1873-4200, Vol. 104, no 1, p. 361-379Article in journal (Refereed)
    Abstract [en]

    The structure and dynamics of two different pH-sensitive liposome systems were investigated by means of cryo-transmission electron microscopy and different photophysical techniques. Both systems consisted of dioleoylphosphatidylethanolamine (DOPE) and contained either oleic acid (OA) or a novel acid-labile polyethylene glycol-conjugated lipid (DHCho-MPEG5000) as stabiliser. Proton induced leakage, lipid mixing and structural changes were studied in the absence and presence of EPC liposomes, as well as in the presence of liposomes designed to model the endosome membrane. Neither DHCho-MPEG5000- nor OA-stabilised liposomes showed any tendency for fusion with pure EPC liposomes or endosome-like liposomes composed of EPC/DOPE/SM/Cho (40/20/6/34 mol.%). Our investigations showed, however, that incorporation of lipids from the pH-sensitive liposomes into the endosome membrane may lead to increased permeability and formation of non-lamellar structures. Taken together the results suggest that the observed ability of DOPE-containing liposomes to mediate cytoplasmic delivery of hydrophilic molecules cannot be explained by a mechanism based on a direct, and non-leaky, fusion between the liposome and endosome membranes. A mechanism involving destabilisation of the endosome membrane due to incorporation of DOPE, seems more plausible.

  • 23.
    Bergstrand, Nill
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Bohl, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Ghaneolhosseine, Hadi
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Jonsson, Markus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Silvander, Mats
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Sjöberg, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Stabilised Liposomes with Double Targeting for Use in BNCT2000In: Contemporary Boron Chemistry / [ed] Matthew Davidson, Cambridge, UK: Royal Society of Chemistry, 2000, p. 131-134Chapter in book (Other academic)
  • 24.
    Bergstrand, Nill
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Aggregate structure in dilute aqueous dispersions of phospholipids, fatty acids and lysophospholipids2001In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 17, no 11, p. 3245-3253Article in journal (Refereed)
    Abstract [en]

    Cryo-transmission electron microscopy (cryo-TEM) was employed to investigate the aggregate structure in dilute aqueous dispersions of egg-phosphatidylcholine (EPC), oleic acid (OA), and the lysophospholipid monooleoylphosphatidylcholine (MOPC). At physiological pH and salt concentration, a relatively monodisperse population of unilamellar liposomes was detected in mixtures containing equimolar concentrations of the three components. Threadlike micelles constituted the dominant aggregate structure in samples containing high concentrations of MOPC. Excess fatty acid forced, on the other hand, the system toward structures with net negative curvature. In the absence of phospholipid, cryo-TEM revealed bilayer fragments in coexistence with threadlike micelles in mixtures containing the same molar amount of MOPC and OA. External addition of MOPC to preformed EPC liposomes gave rise to a concentration dependent evolution of intermediate structures, including open liposomes and bilayer fragments. The structural rearrangements were found to be slow and permitted visualization of a number of interesting transition structures. In addition to the structural studies, static and time-resolved fluorescence measurements were employed to determine some fundamental parameters for MOPC micelles. The results indicate a critical micelle concentration of close to 5 μM and an aggregation number of approximately 142.

  • 25.
    Bergstrand, Nill
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Edwards, Katarina
    Effects caused by PEO-PPO-PEO triblock copolymers on structure and stability of liposomal DOPE dispersions.Article in journal (Refereed)
  • 26.
    Bergstrand, Nill
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical Chemistry. Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Edwards, Katarina
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical Chemistry. Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Effects of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers on structure and stability of liposomal dioleoylphosphatidylethanolamine2004In: Journal of Colloid and Interface Science, Vol. 276, no 2, p. 400-407Article in journal (Refereed)
  • 27.
    Bergström, L. Magnus
    et al.
    Department of Chemistry, Surface, and Corrosion Science, School of Chemical Science and Engineering, KTH Royal Institute of Technology, SE-10044 Stockholm, Sweden.
    Skoglund, Sara
    Department of Chemistry, Surface, and Corrosion Science, School of Chemical Science and Engineering, KTH Royal Institute of Technology, SE-10044 Stockholm, Sweden.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Eriksson, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Grillo, Isabelle
    Institut Laue Langevin, DS/LSS, 6 rue Jules Horowitz, BP156, 38042 Grenoble Cedex 9, France.
    Self-Assembly in Mixtures of an Anionic and a Cationic Surfactant: A Comparison between Small-Angle Neutron Scattering and Cryo-Transmission Electron Microscopy2013In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 29, no 38, p. 11834-11848Article in journal (Refereed)
    Abstract [en]

    The self-assembly in SOS-rich mixtures of the anionic surfactant sodium octyl sulfate (SOS) and the cationic surfactant hexadecyltrimethylammonium bromide (CTAB) has been investigated with the complementary techniques small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). Both techniques confirm the simultaneous presence of open and closed bilayer structures in highly diluted samples as well as the existence of small globular and large elongated micelles at higher concentrations. However, the two techniques sometimes differ with respect to which type of aggregates is present in a particular sample. In particular, globular or wormlike micelles are sometimes observed with cryo-TEM in the vicinity of the micelle-to-bilayer transition, although only bilayers are present according to SANS and the samples appear bluish to the eye. A similar discrepancy has previously been reported but could not be satisfactorily rationalized. On the basis of our comparison between in situ (SANS) and ex situ (cryo-TEM) experimental techniques, we suggest that this discrepancy appears mainly as a result of the non-negligible amount of surfactant adsorbed at interfaces of the thin sample film created during the cryo-TEM specimen preparation. Moreover, from our detailed SANS data analysis, we are able to observe the unusually high amount of free surfactant monomers present in SOS-rich mixtures of SOS and CTAB, and the experimental results give excellent agreement with model calculations based on the Poisson?Boltzmann mean field theory. Our careful comparison between model calculations and experiments has enabled us to rationalize the dramatic microstructural transformations frequently observed upon simply diluting mixtures of an anionic and a cationic surfactant.

  • 28.
    Bergström, L. Magnus
    et al.
    School of Chemical Science and Engineering, Department of Chemistry, Surface and Corrosion Science, KTH Royal Institute of Technology, Sweden.
    Skoglund, Sara
    School of Chemical Science and Engineering, Department of Chemistry, Surface and Corrosion Science, KTH Royal Institute of Technology, Sweden.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Eriksson, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Grillo, Isabelle
    Institut Laue Langevin, DS/LSS, 6 rue Jules Horowitz, B.P. 156, 38042 Grenoble Cedex 9, France.
    Spontaneous Transformations between Surfactant Bilayers of Different Topologies Observed in Mixtures of Sodium Octyl Sulfate and Hexadecyltrimethylammonium Bromide2014In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 30, no 14, p. 3928-3938Article in journal (Refereed)
    Abstract [en]

    The influence of adding salt on the self-assembly in sodium octyl sulfate (SOS)-rich mixtures of the anionic surfactant SOS and the cationic surfactant hexadecyltrimethylammonium bromide (CTAB) have been investigated with the two complementary techniques, small-angle neutron scattering (SANS) and cryo-transmission electron microscopy. We are able to conclude that addition of a substantial amount of inert salt, NaBr, mainly has three effects on the structural behaviors: (i) the micelles become much larger at the transition from micelles to bilayers, (ii) the fraction of bilayer disks increases at the expense of vesicles, and (iii) bilayer aggregates perforated with holes are formed in the most diluted samples. A novel form factor valid for perforated bilayer vesicles and disks is introduced for the first time and, as a result, we are able to directly observe the presence of perforated bilayers by means of fitting SANS data with an appropriate model. Moreover, we are able to conclude that the morphology of bilayer aggregates changes according to the following sequence of different bilayer topologies, vesicles ? disks ? perforated bilayers, as the electrolyte concentration is increased and surfactant mole fraction in the bilayer aggregates approaches equimolarity. We are able to rationalize this sequence of transitions as a result of a monotonous increase of the bilayer saddle-splay constant (k?cbi) with decreasing influence from electrostatics, in agreement with theoretical predictions as deduced from the Poisson?Boltzmann theory.

  • 29. Beugin, S
    et al.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Karlsson, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Ollivon, M
    Lesieur, S
    New sterically stabilized vesicles based on nonionic surfactant, cholesterol, and poly(ethylene glycol)-cholesterol conjugates.1998In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 74, no 6, p. 3198-3210Article in journal (Other academic)
    Abstract [en]

    Monomethoxypoly(ethylene glycol) cholesteryl carbonates (M-PEG-Chol) with polymer chain molecular weights of 1000 (M-PEG1000-Chol) and 2000 (M-PEG2000-Chol) have been newly synthesized and characterized. Their aggregation behavior in mixture with diglycerol hexadecyl ether (C(16)G(2)) and cholesterol has been examined by cryotransmission electron microscopy, high-performance gel exclusion chromatography, and quasielastic light scattering. Nonaggregated, stable, unilamellar vesicles were obtained at low polymer levels with optimal shape and size homogeneity at cholesteryl conjugate/ lipids ratios of 10 mol% M-PEG1000-Chol or 5 mol% M-PEG2000-Chol, corresponding to the theoretically predicted brush conformational state of the PEG chains. At 20 mol% M-PEG1000-Chol or 10 mol% M-PEG2000-Chol, the saturation threshold of the C(16)G(2)/cholesterol membrane in polymer is exceeded, and open disk-shaped aggregates are seen in coexistence with closed vesicles. Higher levels up to 30 mol% lead to the complete solubilization of the vesicles into disk-like structures of decreasing size with increasing PEG content. This study underlines the bivalent role of M-PEG-Chol derivatives: while behaving as solubilizing surfactants, they provide an efficient steric barrier, preventing the vesicles from aggregation and fusion over a period of at least 2 weeks.

  • 30. Bodvik, Rasmus
    et al.
    Dedinaite, Andra
    Karlson, Leif
    Bergström, Magnus
    Bäverbäck, Petra
    Pedersen, Jan Skov
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Karlsson, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Varga, Imre
    Claesson, Per M
    Aggregation and network formation of aqueous methylcellulose and hydroxypropylmethylcellulose solutions.2010In: Colloids and Surfaces A: Physicochemical and Engineering Aspects, ISSN 0927-7757, E-ISSN 1873-4359, Vol. 354, no 1-3, p. 162-171Article in journal (Refereed)
    Abstract [en]

    Solution properties of methylcellulose (MC) and hydroxypropylmethylcellulose (HPMC) have been investigated as a function of temperature and concentration using a broad range of experimental techniques. Novelties include the extensive comparison between MC and HPMC solutions as well as the combination of techniques, and the use of Cryo transmission electron microscopy (Cryo-TEM). The correlation between rheology and light scattering results clearly demonstrates the relation between viscosity change and aggregation. Cryo-TEM images show the network structures formed. Viscosity measurements show that for both MC and HPMC solutions sudden changes in viscosity occur as the temperature is increased. The onset temperature for these changes depends on polymer concentration and heating rate. For both MC and HPMC solutions the viscosity on cooling is very different compared to on heating, demonstrating the slow equilibration time. The viscosity changes in MC and HPMC solutions are dramatically different; for MC solutions the viscosity increases by several orders of magnitude when a critical temperature is reached, whereas for HPMC solutions the viscosity decreases abruptly at a given temperature, followed by an increase upon further heating. Light and (SAXS) small-angle X-ray scattering shows that the increase in viscosity, for MC as well as for HPMC solutions, is due to extensive aggregation of the polymers. Light scattering also provides information on aggregation kinetics. The SAXS measurements allow us to correlate aggregation hysteresis to the viscosity hysteresis, as well as to extract some structural information. Cryo-TEM images give novel information that a fibrillar network is formed in MC solutions, and the strong viscosity increase occurs when this network spans the whole solution volume. For HPMC solutions the behaviour is more complex. The decrease in viscosity can be related to the formation of compact objects, and the subsequent increase to formation of fibrillar structures, which are more linear and less entangled than for MC.

  • 31.
    Bodvik, Rasmus
    et al.
    KTH Royal Institute of Technology, School of Chemical Science and Engineering, Department of Chemistry, Surface and Corrosion Science, Sweden.
    Karlson, Lief
    Akzo Nobel Functional Chemicals AB, Sweden.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Eriksson, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Thormann, Esben
    KTH Royal Institute of Technology, School of Chemical Science and Engineering, Department of Chemistry, Surface and Corrosion Science, Sweden.
    Claesson, Per Martin
    FRIAS, School of Soft Matter Research, University of Freiburg, Germany AND KTH Royal Institute of Technology, School of Chemical Science and Engineering, Department of Chemistry, Surface and Corrosion Science, Sweden.
    Aggregation of modified celluloses in aqueous solution: transition from methylcellulose to hydroxypropylmethylcellulose solution properties induced by a low molecular weight oxyethylene additive2012In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 28, no 38, p. 13562-13569Article in journal (Refereed)
    Abstract [en]

    Temperature effects on viscosity and aggregation behaviour of aqueous solutions of three different cellulose ethers: methylcellulose (MC), hydroxypropylmethylcellulose (HPMC) and ethyl(hydroxyethyl)cellulose (EHEC), were investigated using viscosity and dynamic light scattering measurements as well as Cryo-TEM. In all cases increasing temperature reduces the solvent quality of water, which induces aggregation. It was found that the aggregation rate followed the order EHEC > HPMC > MC, suggesting that cellulose ethers containing some bulky and partly hydrophilic substituents assemble into large aggregates more readly than methylcellulose. This finding is discussed in terms of the organization of the structures formed by the different cellulose ethers. The temperature-dependent association behavior of cellulose ethers was also investigated in a novel way by adding diethyleneglycolmonobutylether (BDG) to methylcellulose aqueous solutions. When the concentration of BDG was at and above 5 wt%, methylcellulose adopted HPMC-like solution behaviour. In particular, a transition temperature where the viscosity was decreasing, prior to increasing at higher temperatures, appeared and the aggregation rate increased. This observation is rationalized by the ability of the amphiphilic BDG to accumulate at non-polar interfaces, and thus also to associate with hydrophobic regions of methylcellulose. In effect BDG is suggested to act as a physisorbed hydrophilic and bulky substituent inducing similar constraints on aggregation as the chemically attached hydroxypropyl groups in HPMC and oligo(ethyleneoxide) chains in EHEC.

  • 32. Boge, Lucas
    et al.
    Bysell, Helena
    Ringstad, Lovisa
    Wennman, David
    Umerska, Anita
    Cassisa, Viviane
    Eriksson, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Joly-Guillou, Marie-Laure
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Andersson, Martin
    Lipid-Based Liquid Crystals As Carriers for Antimicrobial Peptides: Phase Behavior and Antimicrobial Effect2016In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 32, no 17, p. 4217-4228Article in journal (Refereed)
    Abstract [en]

    The number of antibiotic-resistant bacteria is increasing worldwide, and the demand for novel antimicrobials is constantly growing. Antimicrobial peptides (AMPs) could be an important part of future treatment strategies of various bacterial infection diseases. However, AMPs have relatively low stability, because of proteolytic and chemical degradation. As a consequence, carrier systems protecting the AMPs are greatly needed, to achieve efficient treatments. In addition, the carrier system also must administrate the peptide in a controlled manner to match the therapeutic dose window. In this work, lyotropic liquid crystalline (LC) structures consisting of cubic glycerol monooleate/water and hexagonal glycerol monooleate/oleic acid/water have been examined as carriers for AMPs. These LC structures have the capability of solubilizing both hydrophilic and hydrophobic substances, as well as being biocompatible and biodegradable. Both bulk gels and discrete dispersed structures (i.e., cubosomes and hexosomes) have been studied. Three AMPs have been investigated with respect to phase stability of the LC structures and antimicrobial effect: AP114, DPK-060, and LL-37. Characterization of the LC structures was performed using small-angle X-ray scattering (SAXS), dynamic light scattering, zeta-potential, and cryogenic transmission electron microscopy (Cryo-TEM) and peptide loading efficacy by ultra performance liquid chromatography. The antimicrobial effect of the LCNPs was investigated in vitro using minimum inhibitory concentration (MIC) and time-kill assay. The most hydrophobic peptide (AP114) was shown to induce an increase in negative curvature of the cubic LC system. The most polar peptide (DPK-060) induced a decrease in negative curvature while LL-37 did not change the LC phase at all. The hexagonal LC phase was not affected by any of the AMPs. Moreover, cubosomes loaded with peptides AP114 and DPK-060 showed preserved antimicrobial activity, whereas particles loaded with peptide LL-37 displayed a loss in its broad-spectrum bactericidal properties. AMP-loaded hexosomes showed a reduction in antimicrobial activity.

  • 33. Boge, Lukas
    et al.
    Umerska, Anita
    Matougui, Nada
    Bysell, Helena
    Ringstad, Lovisa
    Davoudi, Mina
    Eriksson, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Andersson, Martin
    Cubosomes post-loaded with antimicrobial peptides: characterization, bactericidal effect and proteolytic stability.2017In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 526, no 1-2, p. 400-412Article in journal (Refereed)
    Abstract [en]

    Novel antibiotics, such as antimicrobial peptides (AMPs), have recently attended more and more attraction. In this work, dispersed cubic liquid crystalline gel (cubosomes) was used as drug delivery vehicles for three AMPs (AP114, DPK-060 and LL-37). Association of peptides onto cubosomes was studied at two cubosome/peptide ratios using high performance liquid chromatography, ζ-potential and circular dichroism measurements. AMPs impact on the cubosome structure was investigated using small angle x-ray scattering and cryogenic transmission electron microscopy. The antimicrobial effect of the AMP loaded cubosomes was studied in vitro by minimum inhibitory concentration and time-kill assays. Proteolytic protection was investigated by incubating the formulations with two elastases and the antimicrobial effect after proteolysis was studied using radial diffusion assay. Different association efficacy onto the cubosomes was observed among the AMPs, with LL-37 showing greatest association (>60%). AP114 loaded cubosomes displayed a preserved antimicrobial effect, whereas for LL-37 the broad spectrum bacterial killing was reduced to only comprise Gram-negative bacteria. Interestingly, DPK-060 loaded cubosomes showed a slight enhanced effect against S. aureus and E. coli strains. Moreover, the cubosomes were found to protect LL-37 from proteolytic degradation, resulting in a significantly better bactericidal effect after being subjected to elastase, compared to unformulated peptide.

  • 34. Boge, Lukas
    et al.
    Västberg, Amanda
    Umerska, Anita
    Bysell, Helena
    Eriksson, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Millqvist-Fureby, Anna
    Andersson, Martin
    Freeze-dried and re-hydrated liquid crystalline nanoparticles stabilized with disaccharides for drug-delivery of the plectasin derivative AP114 antimicrobial peptide2018In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 522, p. 126-135Article in journal (Refereed)
    Abstract [en]

    Liquid crystalline nanoparticles (LCNPs), e.g. cubosomes and hexosomes, are receiving more and more attraction as drug delivery vehicles. Dry powder formulation that forms LCNPs upon hydration can be advantageous to make new routes of administration accessible. In this work, we investigate use of three disaccharides (lactose, trehalose and sucrose) as protective matrices for glycerol monooleate based LCNP forming powders produced by freeze-drying. Phase behavior, particle size and size distributions at the different preparation steps were monitored by small angle x-ray scattering (SAXS) and dynamic light scattering (DLS). Particle appearance was imaged by cryogenic transmission electron microscopy (cryo-TEM). Moreover, the therapeutic relevant antimicrobial peptide AP114 (plectasin derivative) was incorporated in the formulations. Peptide encapsulation and release as well as in vitro antibacterial effect were investigated. Results showed that all freeze-dried powders did form particles with liquid crystalline structure upon hydration. However, a phase transition from the bicontinuous cubic Pn3m to the reversed hexagonal was observed, as a consequence of sugar addition and the freeze-drying procedure. Data indicates that trehalose is the preferred choice of lyo-protectant in order to maintain a mono-modal particle size distribution. In addition, antimicrobial activity of AP114-containing formulations was found to be highest for the formulation containing trehalose. The release kinetics of AP114 from the nanoparticles was strongly affected by the dimensions of the hexagonal phase. Larger dimension of the hexagonal phase, significantly improved the release of AP114 and antimicrobial activity of the formulation.

  • 35.
    Bohl Kullberg, E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Capala, J
    Sjöberg, S
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Introductory experiments on ligand liposomes as delivery agents for boronneutron capture therapy2003In: International Journal of Oncology, ISSN 1019-6439, Vol. 23, no 2, p. 461-467Article in journal (Refereed)
    Abstract [en]

    Liposomes are, when coupled to receptor ligands, candidates for receptor mediated delivery of boron for tumour therapy since they have capacity to deliver large amounts of boron per receptor interaction. With EGF-liposomes we present a pegylated ligand liposome delivery vehicle, containing water soluble boronated phenanthridine, WSP1, or water soluble boronated acridine, WSA1, for EGFR targeting. In the case of WSA1 a ligand dependent uptake was obtained and the boron uptake was as good as if free WSA1 was given. No ligand dependent boron uptake was seen for WSP1 containing liposomes. Thus, WSA1 is a candidate for further studies. Approximately 10(5) boron atoms were in each liposome. A critical assessment indicates that after optimization up to 10(6) boron atoms can be loaded. Since it is known that, for therapeutic effect, approximately 10(8)-10(9) boron atoms are needed in a single tumour cell it is realized that 10(2)-10(3) receptor interactions are needed to meet the demand. Tests applying cultured glioma cells indicate, without optimization of the delivery conditions, a boron uptake in the ppm range, which is necessary for successful BNCT. Thus, it seems possible to kill micro-invasive tumour cells with targeted liposomes if the delivery conditions are optimal.

  • 36.
    Bohl Kullberg, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Bergstrand, Nill
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Johnsson, Markus
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Sjöberg, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Development of EGF-conjugated liposomes for targeted delivery of boronated DNA-binding agents2002In: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 13, no 4, p. 737-743Article in journal (Refereed)
    Abstract [en]

    Liposomes are of interest as drug delivery tools for therapy of cancer and infectious diseases. We investigated conjugation of epidermal growth factor, EGF, to liposomes using the micelle-transfer method. EGF was conjugated to the distal end of PEG−DSPE lipid molecules in a micellar solution and the EGF−PEG−DSPE lipids were then transferred to preformed liposomes, either empty or containing the DNA-binding compound, water soluble acridine, WSA. We found that the optimal transfer conditions were a 1-h incubation at 60 °C. The final conjugate, 125I-EGF−liposome−WSA, contained approximately 5 mol % PEG, 10−15 EGF molecules at the liposome surface, and 104 to 105 encapsulated WSA molecules could be loaded. The conjugate was shown to have EGF-receptor-specific cellular binding in cultured human glioma cells.

  • 37.
    Boija, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Lundquist, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Evaluation of bilayer disks as plant cell membrane models in partition studies2007In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 364, no 2, p. 145-152Article in journal (Refereed)
    Abstract [en]

    We have studied the partitioning of a set of phenolic compounds used as lignin precursor models into lipid bilayer disks and liposomes. The bilayer disks are open bilayer structures stabilized by polyethylene glycol-conjugated lipids. Our results indicate that disks generate more accurate partition data than do liposomes. Furthermore, we show that the partitioning into the membrane phase is reduced slightly if disks composed of 1,2-distearoyl-sn-glycero-3-phosphocholine and cholesterol are exchanged for disks with a lipid composition mimicking that of the root tissue of Zea mays L.

  • 38.
    Boija, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Lundquist, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Nilsson, Mikael
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar, Sweden.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Isaksson, Roland
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar, Sweden.
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Bilayer disk capillary electrophoresis: a novel method to study drug partitioning into membranes2008In: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 29, no 16, p. 3377-3383Article in journal (Refereed)
    Abstract [en]

    CE in the presence of lipid bilayer disks was introduced as a new approach in membrane partitioning studies. The disks were used as a pseudostationary phase in the partial-filling mode of CE and the partitioning of cationic drugs was determined. The migration times of the analytes increased linearly with the lipid amount in the system. An appropriate algorithm for the calculation of a partition coefficient is presented. In the disk-shaped bilayers, which have excellent stability and shelf life, all of the lipids are readily available for interaction and the disks can be used as realistic cell membrane models.

  • 39.
    Boomer, Jeremy A.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Inerowicz, Halina D.
    Zhang, Zhi-Yi
    Bergstrand, Nill
    Edwards, Katarina
    Kim, Jong-Mok
    Thompson, David H.
    Acid-Triggered Release from Sterically Stabilized Fusogenic Liposomes via a Hydrolytic DePEGylation Strategy2003In: Langmuir, Vol. 19, p. 6408-6415Article in journal (Refereed)
  • 40.
    Bramer, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Göran, Karlsson
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Effects of pH and ionic strength on catanionic drug-surfactant mixtures used for prolonged release from gels.2007In: Journal of drug delivery science and technology, ISSN 1773-2247, Vol. 17, no 4, p. 285-291Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate the influence of pH and ionic strength on the phase behavior of two different catanionic drug-surfactant mixtures, and to study drug release from gels facilitated by the catanionic aggregates. Simplified phase diagrams were constructed for diphenhydramine or tetracaine mixed with SDS, varying the pH approximately between 6 and 11, and the NaCI concentration from 0.45 to 1.8%. The phases formed were studied visually, rheologically and with cryo-TEM. Some mixtures containing catanionic vesicles and micelles were selected for drug release studies from gels, varying the pH and NaCI concentration here as well. Both catanionic systems investigated proved relatively resilient to changes in the ionic strength. Changes in pH, on the other hand, caused marked effects to the phase behavior in both systems. The influence of pH was particularly strong in the drug-rich part of the tetracaine/SDS system, where increasing the pH causes precipitation. As expected, the drug release in both systems was somewhat affected by changes in both pH and ionic strength, but remained in all cases significantly prolonged as compared to the release of free, non-complexed, drug. These studies show that catanionic mixtures may be used to obtain prolonged drug release from gels, and that the concept also works when the gels are exposed to a pH that is a couple of units above the pKa of the cationic component. Furthermore, the ionic strength has no pronounced effect on the drug release, as long as it is kept within reasonable pharmaceutical levels.

  • 41.
    Bramer, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Paulsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Catanionic drug-surfactant mixtures: Phase behavior and sustained release from gels2003In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 20, no 10, p. 1661-1667Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To study mixtures of SDS and the drugs diphenhydramine, tetracaine, and amitriptyline to compile phase diagrams and to investigate the use of interesting phases for sustained release from gels. METHODS: Phase diagrams were composed by studying large numbers of different compositions of negatively charged SDS and positively charged drug compounds visually, rheologically, and by cryotransmission electron microscopy. Drug release from Carbopol 940 and agar gels containing interesting phases, e.g., vesicle and branched micelle phases, was measured in vitro by the USP paddle method. RESULTS: Vesicles and elongated and branched micelles were formed on the SDS-rich side in all three systems examined. The tetracaine system differed from the other two in that it showed a vesicle area in the drug-rich side. Release of diphenhydramine from Carbopol 940 gels was slowed by at least a factor of 10 when in the form of vesicles or branched micelles. The same delay was found for both drug-rich and SDS-rich tetracaine vesicles. CONCLUSIONS: Mixtures of SDS and positively charged drugs form the same interesting phases as traditional catanionic mixtures. This may prove useful in obtaining functional controlled-release systems when using gels as drug carriers.

  • 42.
    Carlsson, J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Bohl, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Nilsson, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sjöström, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sjöberg, S
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Cellular spheroids as a micrometastasis model in preclinical tests of boron neutron capture therapy2001In: Frontiers in Neutron Capture Therapy, volume 1: Medicine and Physics / [ed] M. Frederick Hawthorne, Kenneth Shelly, Richard J Wiersema, 2001, p. 109-Conference paper (Other academic)
  • 43.
    Carlsson, Jörgen
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bohl Kullberg, Erika
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Capala, Jacek
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sjöberg, Stefan
    Edwards, Katarina
    Department of Physical Chemistry.
    Gedda, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ligand liposomes and boron neutron capture therapy2003In: Journal of Neuro-Oncology, Vol. 62, p. 47-Article in journal (Refereed)
  • 44.
    Carlsson, Jörgen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ghaneolhosseini, H
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Johnsson, M
    Sjöberg, S
    Stabilised liposomes with double targeting intendent for use in BNCT2001In: Frontiers in Neutron Capture Therapy: Volume 1 / [ed] M Frederick Hawthorne, Kenneth Shelly, Richard J Wiersema, 2001, p. 184-Conference paper (Other academic)
  • 45. Chiu, Gigi N C
    et al.
    Abraham, Sheela A
    Ickenstein, Ludger M
    Ng, Rebecca
    Karlsson, Göran
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical Chemistry. Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Edwards, Katarina
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical Chemistry. Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Wasan, Ellen K
    Bally, Marcel B
    Encapsulation of doxorubicin into thermosensitive liposomes via complexation with the transition metal manganese.2005In: J Control Release, ISSN 0168-3659, Vol. 104, no 2, p. 271-288Article in journal (Refereed)
  • 46.
    Cui, Zhong-Kai
    et al.
    Department of Chemistry, Centre for Self-Assembled Chemical Structures (CSACS), Université de Montréal, Canada.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Orellana, Alejandro Nieto
    INSERM U1066, Micro et Nanomédecines Biomimétiques-MINT, France AND LUNAM Université, UMR-S1066, Angers F-49933, France.
    Bastiat, Guillaume
    INSERM U1066, Micro et Nanomédecines Biomimétiques-MINT, France AND LUNAM Université, UMR-S1066, Angers F-49933, France.
    Benoit, Jean-Pierre
    INSERM U1066, Micro et Nanomédecines Biomimétiques-MINT, France AND LUNAM Université, UMR-S1066, Angers F-49933, France.
    Lafleur, Michel
    Department of Chemistry, Centre for Self-Assembled Chemical Structures (CSACS), Université de Montréal, Canada.
    Impact of interfacial cholesterol-anchored polyethylene glycol on sterol-rich non-phospholipid liposomes2014In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 428, p. 111-120Article in journal (Refereed)
    Abstract [en]

    Hypothesis

    Liposomes made of single-chain amphiphiles and a large amount of sterols display several advantages including a limited permeability. In the present paper, we examine the possibility to prepare such non-phospholipid liposomes with interfacial polyethylene glycol (PEG) in order to improve their circulation in the blood stream. Cholesterol (Chol) was chosen as the PEG anchor.

    Experiments

    The phase behavior of mixtures of palmitic acid (PA) and cholesterol including various proportions of PEGylated cholesterol (PEG-Chol) was characterized. In conditions leading to the formation of fluid bilayers, properties of the resulting liposomes were assessed.

    Findings

    Up to 20 mol% of PEGylated cholesterol could be introduced without significant perturbations in fluid bilayers made of PA and cholesterol. With 10 mol% PEG-Chol, PA/Chol/PEG-Chol liposomes showed a very limited permeability to calcein and doxorubicin. Doxorubicin could be actively loaded in PA/Chol/PEG-Chol liposomes with a high drug loading efficiency and a high drug to lipid ratio. Pharmaco-kinetic experiments in rats indicated that interfacial PEG reduced the clearance of PA/Chol liposomes compared to the naked ones. However the lifetime of these non-phospholipid liposomes in the blood circulation was considerably shorter than that observed for control PEGylated phospholipid liposomes, a phenomenon associated with the negative interfacial charge of the PA/Chol/PEG-Chol liposomes. 

  • 47.
    Dew, Noel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Gel formation in systems composed of drug containing catanionic vesicles and oppositely charged hydrophobically modified polymer.2009In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 70, no 2, p. 187-197Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to explore if mixtures of drug containing catanionic vesicles and polymers give rise to gel formation, and if so, if drug release from these gels could be prolonged. Catanionic vesicles formed from the drug substances alprenolol or tetracaine, and the oppositely charged surfactant sodium dodecyl sulphate were mixed with polymers. Three polymers with different properties were employed: one bearing hydrophobic modifications, one positively charged and one positively charged polymer bearing hydrophobic modifications. The structure of the vesicles before and after addition of polymer was investigated by using cryo-TEM. Gel formation was confirmed by using rheological measurements. Drug release was studied using a modified USP paddle method. Gels were observed to form only in the case when catanionic vesicles, most likely with a net negative charge, were mixed with positively charged polymer bearing lipophilic modifications. The release of drug substance from these systems, where the vesicles are not trapped within the gel but constitute a founding part of it, could be significantly prolonged. The drug release rate was found to depend on vesicle concentration to a higher extent than on polymer concentration.

  • 48.
    Dew, Noel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Eriksson, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Björk, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Gel formulations containing catanionic vesicles composed of alprenolol and SDS: effects of drug release and skin penetration on aggregate structure2012In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 89, p. 53-60Article in journal (Refereed)
    Abstract [en]

    To fully utilize the extended contact time of gel formulations a novel formulation with drug containing catanionic aggregates offering prolonged drug release and skin penetration were investigated. This study aimed to further explore the drug release process from catanionic vesicles in gels. Catanionic vesicles were formed from alprenolol and sodium dodecyl sulphate. Physical gels composed of catanionic vesicles and a SoftCAT polymer were used as well as covalent Carbopol gels. Drug release was measured in vitro using a modified USP paddle method and the skin penetration was studied using dermatomized pig ear skin mounted in horizontal Ussing chambers. The aggregate structure was visualized with cryo-TEM during the drug release and skin penetration process. The study results show that catanionic vesicles are present in the formulations throughout the drug release process and during the clinically relevant skin application time. Hence, the decreased skin penetration rate stems from the prolonged release of drug substance from the gels. The rheological investigation shows that the gel structure of the physically cross-linked gels is maintained even as the drug substance is released and the gel volume is decreased.These findings indicate that the applicability of formulations like these is a future possibility.

  • 49. Dos Santos, Nancy
    et al.
    Allen, Christine
    Doppen, Anne-Marie
    Anantha, Malathi
    Cox, Kelly A K
    Gallagher, Ryan C
    Karlsson, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry.
    Kenner, Gail
    Samuels, Lacey
    Webb, Murray S
    Bally, Marcel B
    Influence of poly(ethylene glycol) grafting density and polymer length on liposomes: Relating plasma circulation lifetimes to protein binding2007In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1768, no 6, p. 1367-1377Article in journal (Refereed)
    Abstract [en]

    The incorporation of poly(ethylene glycol) (PEG)-conjugated lipids in lipid-based carriers substantially prolongs the circulation lifetime of liposomes. However, the mechanism(s) by which PEG-lipids achieve this have not been fully elucidated. It is believed that PEG-lipids mediate steric stabilization, ultimately reducing surface-surface interactions including the aggregation of liposomes and/or adsorption of plasma proteins. The purpose of the studies described here was to compare the effects of PEG-lipid incorporation in liposomes on protein binding, liposome-liposome aggregation and pharmacokinetics in mice. Cholesterol-free liposomes were chosen because of their increasing importance as liposomal delivery systems and their marked sensitivity to protein binding and aggregation. Specifically, liposomes containing various molecular weight PEG-lipids at a variety of molar proportions were analyzed for in vivo clearance, aggregation state (size exclusion chromatography, quasi-elastic light scattering, cryo-transmission and freeze fracture electron microscopy) as well as in vitro and in vivo protein binding. The results indicated that as little as 0.5 mol% of 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE) modified with PEG having a mean molecular weight of 2000 (DSPE-PEG(2000)) substantially increased plasma circulation longevity of liposomes prepared of 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC). Optimal plasma circulation lifetimes could be achieved with 2 mol% DSPE-PEG(2000). At this proportion of DSPE-PEG(2000), the aggregation of DSPC-based liposomes was completely precluded. However, the total protein adsorption and the protein profile was not influenced by the level of DSPE-PEG(2000) in the membrane. These studies suggest that PEG-lipids reduce the in vivo clearance of cholesterol-free liposomal formulations primarily by inhibition of surface interactions, particularly liposome-liposome aggregation.

  • 50. Dos Santos, Nancy
    et al.
    Cox, Kelly A
    McKenzie, Cheryl A
    van Baarda, Floris
    Gallagher, Ryan C
    Karlsson, Göran
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical Chemistry. Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Edwards, Katarina
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical Chemistry. Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Mayer, Lawrence D
    Allen, Christine
    Bally, Marcel B
    pH gradient loading of anthracyclines into cholesterol-free liposomes: enhancing drug loading rates through use of ethanol.2004In: Biochim Biophys Acta, ISSN 0006-3002, Vol. 1661, no 1, p. 47-60Article in journal (Refereed)
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