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  • 1.
    Berglin, Cecilia Engmer
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Pierre, Pernilla Videhult
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Ekborn, Andreas
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Bramer, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Hultcrantz, Malou
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Otorhinolaryngol, Stockholm, Sweden..
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Local treatment of the inner ear: A study of three different polymers aimed for middle ear administration2015In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 135, no 10, p. 985-994Article in journal (Refereed)
    Abstract [en]

    Conclusion: A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination. Objectives: Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration. Method: The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection. Results: The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration.

  • 2. Berglin, Cecilia Engmér
    et al.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bramer, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Counter, S Allen
    Klason, Tomas
    Ekborn, Andreas
    Magnetic Resonance Imaging of the Middle and Inner Ear After Intratympanic Injection of a Gadolinium-Containing Gel2014In: Otology and Neurotology, ISSN 1531-7129, E-ISSN 1537-4505, Vol. 35, no 3, p. 526-532Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate the distribution and elimination of a gadolinium containing high viscosity formulation of sodium hyaluronan (HYA gel) after injection to the middle ear.

    MATERIALS AND METHODS:

    The T1 contrast agent gadolinium-diethylenetriamine pentaacetic acid-bis methylamine (Gd-DTPA-BMA) was added to HYA gel and delivered to the middle ear of 13 albino guinea pigs by 3 different ways of injection. Magnetic resonance imaging was performed with a 4.7 T MRI system using a T1-weighted 3-dimentional rapid acquisition with relaxation enhancement sequence.

    RESULTS:

    An injection technique where the Gd-DTPA-BMA-containing HYA gel was delivered to the middle ear through a percutaneous injection through the auditory bulla after a small incision had been made in the tympanic membrane gave the best filling of the middle ear, covering the cochlea and the region of the round window niche for 24 hours in a majority of the ears studied. Ears injected without an incision in the tympanic membrane showed an immediate uptake of Gd-DTPA-BMA in the inner ear as a sign of rupture of the round window membrane.

    CONCLUSION:

    A percutaneous injection of a HYA gel into the tympanic bulla is distributed in a predictable way and gives a good filling of the middle ear cavity. The HYA gel remains in close vicinity to the RWM for more than 24 hours. Injection should be performed after an incision of the tympanic membrane has been made to prevent rupture of the round window membrane.

  • 3. Bergström, L Magnus
    et al.
    Bramer, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Synergistic effects in mixtures of oppositely charged surfactants as calculated from the Poisson-Boltzmann theory: A comparison between theoretical predictions and experiments2008In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 322, no 2, p. 589-595Article in journal (Refereed)
    Abstract [en]

    Critical micelle concentrations in mixtures of an anionic surfactant and a cationic amphiphilic drug have been investigated using a model-independent procedure to quantify observed synergistic effects. Experimental results were compared with a theory based on the Poisson-Boltzmann mean field approximation of a charged interface with a diffuse layer of counterions. Explicit expressions for the activity coefficients from which the critical micelle concentration can be calculated and quantitatively predicted have been derived and excellent agreement between experimental data and theory was obtained. As a result, we demonstrate that it is possible to rationalize and predict the magnitude of synergism in mixtures of oppositely charged surfactants in the presence of added salt.

  • 4.
    Bramer, Tobias
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Dew, Noel
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Catanionic mixtures involving a drug: a rather general concept that can be utilized for prolonged drug release from gels.2006In: J Pharm Sci, ISSN 0022-3549, Vol. 95, no 4, p. 769-80Article in journal (Refereed)
  • 5.
    Bramer, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Dew, Noel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Pharmaceutical applications for catanionic mixtures2007In: Journal of Pharmacy and Pharmacology (JPP), ISSN 0022-3573, E-ISSN 2042-7158, Vol. 59, no 10, p. 1319-1334Article, review/survey (Refereed)
    Abstract [en]

    Mixtures of oppositely charged surfactants, so called catanionic mixtures, are a growing area of research. These mixtures have been shown to form several different types of surfactant aggregates, such as micelles of various forms and sizes, and lamellar structures, such as vesicles. In this review, a short introduction to the field of catanionic mixtures is presented and the pharmaceutical possibilities offered by such mixtures are reviewed. There are several interesting ideas on how to apply catanionic mixtures to improve the delivery of, for example, drug compounds and DNA, or for HIV treatment.

  • 6.
    Brohede, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Bramer, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Electrodynamic Investigations of Ion Transport and Structural Properties in Drug-Containing Gels: Dielectric Spectroscopy and Transient Current Measurements on Catanionic Carbopol Systems2005In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 109, no 32, p. 15250-15255Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to show the potential of using electrodynamic methods as characterization tools in the controlled drug release process, on complex drug release systems. The two formulations under study were a Carbopol gel containing diphenhydramine and an identical gel also containing the surfactant sodium dodecyl sulfate which forms catanionic vesicles with the diphenhydramine. The average diffusion coefficients were calculated from both the dielectric spectroscopy and the transient current measurements. Comparing the herein-obtained diffusion coefficients with those obtained in another study using a traditional USP technique for the same system, the values are virtually the same. The two electrodynamic methods proved to be potentially valuable tools for obtaining information about the concentration and the motion of the drug molecules inside the gel. The transient current measurements are particularly interesting in this case, as the method gives information not only on an average level, but also of the different charged moieties separately. Interestingly, it seems that the methods also are applicable for obtaining information about the mesh size in the gel.

  • 7.
    Dew, Noel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bramer, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Catanionic aggregates formed from drugs and lauric or capric acids enable prolonged release from gels2008In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 323, no 2, p. 386-394Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to add to the range of charged surfactants that can be used to form catanionic aggregates with oppositely charged surface active drug substances, and to apply these aggregates to prolong drug release from gels. The surfactants used in this study, lauric and capric acids are of natural origin-unlike traditionally used, synthetic, surfactants. The mixtures of drug substances and oppositely charged surfactants were studied visually and with cryogenic transmission electron microscopy. Drug release from gels was studied with a modified USP paddle method. This study shows that lauric and capric acids are as, or even more, active in forming catanionic aggregates than traditionally used surfactants such as sodium dodecyl sulfate. It is shown that the length of the hydrophobic part of the surfactant plays an important role in the formation of pharmaceutically interesting catanionic aggregates. As seen in previous studies, using catanionic vesicles prolongs the drug release from gels and decreases the apparent diffusion coefficient by a factor of 10-50, compared to a gel containing only drug substance.

  • 8. Engmer Berglin, Cecilia
    et al.
    Videhult Pierre, Pernilla
    Bramer, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Ehrsson, Hans
    Eksborg, Staffan
    Laurell, Göran
    Prevention of cisplatin-induced hearing loss by administration of a thiosulfate-containing gel to the middle ear in a guinea pig model2011In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 68, no 6, p. 1547-1556Article in journal (Refereed)
    Abstract [en]

    Thiosulfate may reduce cisplatin-induced ototoxicity, most likely by relieving oxidative stress and by forming inactive platinum complexes. This study aimed to determine the concentration and protective effect of thiosulfate in the cochlea after application of a thiosulfate-containing high viscosity formulation of sodium hyaluronan (HYA gel) to the middle ear prior to i.v. injection of cisplatin in a guinea pig model. The release of thiosulfate (0.1 M) from HYA gel (0.5% w/w) was explored in vitro. Thiosulfate in the scala tympani perilymph of the cochlea 1 and 3 h after application of thiosulfate in HYA gel to the middle ear was quantified with HPLC and fluorescence detection. Thiosulfate in blood and CSF was also explored. The potential otoprotective effect was evaluated by hair cell count after treatment with thiosulfate in HYA gel applied to the middle ear 3 h prior to cisplatin injection (8 mg/kg b.w.). HYA did not impede the release of thiosulfate. Middle ear administration of thiosulfate in HYA gel gave high concentrations in the scala tympani perilymph while maintaining low levels in blood, and it protected against cisplatin-induced hair cell loss. HYA gel is an effective vehicle for administration of thiosulfate to the middle ear. Local application of a thiosulfate-containing HYA gel reduces the ototoxicity of cisplatin most likely without compromising its antineoplastic effect. This provides a minimally invasive protective treatment that can easily be repeated if necessary.

  • 9.
    Merclin, Nadia
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Bramer, Tobias
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Iontophoretic delivery of 5-aminolevulinic acid and its methyl ester using a carbopol gel as vehicle.2004In: J Control Release, ISSN 0168-3659, Vol. 98, no 1, p. 57-65Article in journal (Other scientific)
1 - 9 of 9
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