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Lu, Xi
Publications (10 of 10) Show all publications
Yang, J., Alvebratt, C., Lu, X., Bergström, C., Strömme, M. & Welch, K. (2018). Amorphous Magnesium Carbonate Nanoparticles with Strong Stabilizing Capability for Amorphous Ibuprofen. International Journal of Pharmaceutics, 548(1), 515-521
Open this publication in new window or tab >>Amorphous Magnesium Carbonate Nanoparticles with Strong Stabilizing Capability for Amorphous Ibuprofen
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2018 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 548, no 1, p. 515-521Article in journal (Refereed) Published
Abstract [en]

Formulating active pharmaceutical ingredients (APIs) in the amorphous state can increase their apparent aqueous solubility and dissolution rate and consequently improve their bioavailability. This study demonstrates, for the first time, the ability to stabilize an API in the amorphous state using a solid dispersion of magnesium carbonate nanoparticles within the API. Specifically, high proportions of ibuprofen were able to be stabilized in the amorphous state using as little as 17% wt/wt amorphous magnesium carbonate nanoparticles, and drug release rates 83 times faster than from the crystalline state were achieved. Biocompatibility of the nanoparticles was demonstrated in vitro using human dermal fibroblasts and stability of the nanocomposite formulation was verified with a storage time of six months. The success of this novel formulation provides a promising approach for achieving improved apparent solubility and enhanced bioavailability of drugs.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Magnesium carbonate, Nanoparticles, Nanocomposite, Amorphous, Ibuprofen, Solubility, Dissolution
National Category
Nano Technology Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-354506 (URN)10.1016/j.ijpharm.2018.07.021 (DOI)000440552100050 ()29981897 (PubMedID)
Funder
Swedish Research Council
Available from: 2018-06-20 Created: 2018-06-20 Last updated: 2019-11-07Bibliographically approved
Díez-Escudero, A., Montserrat, E., Bonany, M., Lu, X., Persson, C. & Ginebra, M.-P. (2018). Heparinization of Beta Tricalcium Phosphate: Osteo-immunomodulatory Effects. Advanced Healthcare Materials, 7(5), Article ID 1700867.
Open this publication in new window or tab >>Heparinization of Beta Tricalcium Phosphate: Osteo-immunomodulatory Effects
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2018 (English)In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 7, no 5, article id 1700867Article in journal (Refereed) Published
Abstract [en]

Immune cells play a vital role in regulating bone dynamics. This has boosted the interest in developing biomaterials that can modulate both the immune and skeletal systems. In this study, calcium phosphates discs (i.e., beta-tricalcium phosphate, β-TCP) are functionalized with heparin to investigate the effects on immune and stem cell responses. The results show that the functionalized surfaces downregulate the release of hydrogen peroxide and proinflammatory cytokines (tumor necrosis factor alpha and interleukin 1 beta) from human monocytes and neutrophils, compared to nonfunctionalized discs. The macrophages show both elongated and round shapes on the two ceramic substrates, but the morphology of cells on heparinized β-TCP tends toward a higher elongation after 72 h. The heparinized substrates support rat mesenchymal stem cell (MSC) adhesion and proliferation, and anticipate the differentiation toward the osteoblastic lineage as compared to β-TCP and control. The coupling between the inflammatory response and osteogenesis is assessed by culturing MSCs with the macrophage supernatants. The downregulation of inflammation in contact with the heparinized substrates induces higher expression of bone-related markers by MSCs.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2018
Keywords
calcium phosphates; heparinization; inflammation; osteogenesis
National Category
Medical Materials Biomaterials Science
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-340741 (URN)10.1002/adhm.201700867 (DOI)000426758500005 ()
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), STINT-IG2011-2047
Available from: 2018-02-02 Created: 2018-02-02 Last updated: 2018-08-09Bibliographically approved
Pujari-Palmer, S., Lu, X., Singh, V. P., Engman, L., Pujari-Palmer, M. & Karlsson Ott, M. (2017). Incorporation and delivery of an organoselenium antioxidant from a brushite cement. Materials letters (General ed.), 197, 115-119
Open this publication in new window or tab >>Incorporation and delivery of an organoselenium antioxidant from a brushite cement
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2017 (English)In: Materials letters (General ed.), ISSN 0167-577X, E-ISSN 1873-4979, Vol. 197, p. 115-119Article in journal (Refereed) Published
Abstract [en]

An inflammatory reaction occurs following biomaterial implantation in the body, which produce toxic byproducts such as reactive oxygen species (ROS). Although ROS is required to clear the wound, excessive ROS can damage the tissue around the implant site, eventually leading to implant failure. One approach to control the inflammatory response is to incorporate an antioxidant into the biomaterial in order to scavenge ROS produced by activated phagocytes. In the present study, an organoselenium antioxidative compound was incorporated into a brushite cement, with the goal of scavenging ROS generated from activated primary human mononuclear leukocytes (MNCs), in vitro. The effect of the antioxidant on the physical properties of brushite cement, and its release from the cement were investigated via compressive strength, setting time, phase composition, and UV spectroscopy analysis. The physical properties of brushite remained unchanged following incorporation of the antioxidant. The antioxidant was slowly released from the cement, following a non-Fickian transport mechanism, with approximately 60% of the loaded antioxidant released over five days. The released antioxidant was then tested for its ability to scavenge ROS released by MNCs using the luminol amplified chemiluminescence assay. The results show that antioxidative released at both early stages (24 h) and late stages (120 h) retained its scavenging capacity and effectively reduced ROS production. These results indicate that brushite cements loaded with organoselenium compounds can modulate ROS production after implantation and potentially modulate the inflammatory response to improve device integration.

Keywords
Antioxidants, Reactive oxygen species, Calcium phosphate cements, Inflammation, Biomaterial, Drug delivery
National Category
Materials Engineering
Identifiers
urn:nbn:se:uu:diva-322444 (URN)10.1016/j.matlet.2017.03.139 (DOI)000399500300031 ()
Funder
Carl Tryggers foundation , CTS 13:346Magnus Bergvall Foundation, 2015-01111Stiftelsen Längmanska kulturfonden, 16-2-41
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2017-05-23Bibliographically approved
Singh, V. P., Poon, J.-f., Yan, J., Lu, X., Karlsson Ott, M., Butcher, R. J., . . . Engman, L. (2017). Nitro-, Azo-, and Amino Derivatives of Ebselen: Synthesis, Structure, and Cytoprotective Effects. Journal of Organic Chemistry, 82(1), 313-321
Open this publication in new window or tab >>Nitro-, Azo-, and Amino Derivatives of Ebselen: Synthesis, Structure, and Cytoprotective Effects
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2017 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 82, no 1, p. 313-321Article in journal (Refereed) Published
Abstract [en]

Novel azo-bis-ebselen compounds 7 were prepared by reduction of 7-nitro-2-aryl-1,2-benzisoselenazol-3(2H)ones 3 and 6 with sodium benzenetellurolate; NaTeC6H5, and by reaction of 2-bromo-3-nitrobenzamides with Na2Se2. The X-ray structure of 7b showed that the molecule, due to strong intramolecular secondary Se center dot center dot center dot N interactions, is completely planar. Azo-compounds 7 upon further reaction with NaTeC6H5 were reductively cleaved to provide 2 equiv of the corresponding aromatic amine. The weak Se-N bond was not stable enough to survive the reaction conditions, and diselenides 8 were isolated after workup. Whereas azo-bis-ebselens 7 were poor mimics of the glutathione peroxidase (GPx)-enzymes, nitroebselens 3, 6, and 11b and diselenides 8 were 3-6-fold more active than ebselen. Based on Se-77 NMR. spectroscopy, a catalytic cycle for diselenide 8b, involving aminoebselen 14, was proposed. As assessed by chemiluminescence measurements, the good GPx-mimics could reduce production of reactive oxygen species (ROS) in stimulated human mononuclear cells more efficiently than Trolox. No toxic effects of the, compounds were seen in MC3T3-cells at 25 mu M.

National Category
Organic Chemistry Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-312514 (URN)10.1021/acs.joc.6b02418 (DOI)000391781900030 ()27966348 (PubMedID)
Funder
ÅForsk (Ångpanneföreningen's Foundation for Research and Development), 16-364Stiftelsen Olle Engkvist Byggmästare, 2016/159Carl Tryggers foundation , CTS 13:346
Available from: 2017-01-10 Created: 2017-01-10 Last updated: 2017-11-29Bibliographically approved
Lu, X., Mestres, G., Singh, V. P., Effati, P., Poon, J.-F., Engman, L. & Marjam, K. O. (2017). Selenium- and tellurium-based antioxidants for modulating inflammation and effects on osteoblastic activity. Antioxidants, 6(13), 1-13
Open this publication in new window or tab >>Selenium- and tellurium-based antioxidants for modulating inflammation and effects on osteoblastic activity
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2017 (English)In: Antioxidants, E-ISSN 2076-3921, Vol. 6, no 13, p. 1-13Article in journal (Refereed) Published
Abstract [en]

Increased oxidative stress plays a significant role in the etiology of bone diseases. Heightened levels of H2O2 disrupt bone homeostasis, leading to greater bone resorption than bone formation. Organochalcogen compounds could act as free radical trapping agents or glutathione peroxidase mimetics, reducing oxidative stress in inflammatory diseases. In this report, we synthesized and screened a library of organoselenium and organotellurium compounds for hydrogen peroxide scavenging activity, using macrophagic cell lines RAW264.7 and THP-1, as well as human mono- and poly-nuclear cells. These cells were stimulated to release H2O2, using phorbol 12-myristate 13-acetate, with and without organochalogens. Released H2O2 was then measured using a chemiluminescent assay over a period of 2 h. The screening identified an organoselenium compound which scavenged H2O2 more effectively than the vitamin E analog, Trolox. We also found that this organoselenium compound protected MC3T3 cells against H2O2 -induced toxicity, whereas Trolox did not. The organoselenium compound exhibited no cytotoxicity to the cells and had no deleterious effects on cell proliferation, viability, or alkaline phosphatase activity. The rapidity of H2O2 scavenging and protection suggests that the mechanism of protection is due to the direct scavenging of extracellular H2O2. This compound is a promising modulators of inflammation and could potentially treat diseases involving high levels of oxidative stress.

Keywords
antioxidants, reactive oxygen species, inflammation
National Category
Immunology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-315564 (URN)10.3390/antiox6010013 (DOI)000398677900012 ()
Available from: 2017-02-15 Created: 2017-02-15 Last updated: 2017-05-18Bibliographically approved
Pujari-Palmer, S., Lu, X. & Karlsson Ott, M. (2017). The Influence of Hydroxyapatite Nanoparticle Morphology on Embryonic Development in a Zebrafish Exposure Model. NANOMATERIALS, 7(4), Article ID 89.
Open this publication in new window or tab >>The Influence of Hydroxyapatite Nanoparticle Morphology on Embryonic Development in a Zebrafish Exposure Model
2017 (English)In: NANOMATERIALS, ISSN 2079-4991, Vol. 7, no 4, article id 89Article in journal (Refereed) Published
Abstract [en]

Nanomaterials are used in many different industries such as cosmetics, food, clothing, and electronics. There is increasing concern that exposure to nanoparticles (NPs) during pregnancy can adversely affect fetal development. It is well known that the size, charge, and chemistry of a nanoparticle can modulate embryological development. The role that particle morphology plays on early development, however, is still widely unknown. The present study aims to investigate the effect of hydroxyapatite nanoparticle (HANP) morphology on embryological development in a zebrafish exposure model. Four distinct HANP morphologies (dots, long rods, sheets, and fibers) were fabricated and characterized. Zebrafish embryos were exposed to HANPs (0-100 mg/L), and viability and developmental deformities were evaluated for up to 5 days post-fertilization (dpf). Malformations such as pericardial edema and axial curvature were apparent in embryos as early as 1 dpf, following exposure to the dot and fiber particles, and developed in embryos by 3 dpf in the sheet and long rod particle groups. Minimal death was observed in response to dot, long rod, and sheet particles (<= 25%), while fiber particles induced overwhelming toxicity (<= 60%) after 1 dpf, and complete toxicity during all subsequent time points. Collectively, these results suggest that nanoparticle morphology can significantly impact embryological development and should be a required consideration when designing nanomaterials for commercial use.

Keywords
nanoparticle morphology, hydroxyapatite, zebrafish development
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-329136 (URN)10.3390/nano7040089 (DOI)000404048100018 ()
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2017-10-10 Created: 2017-10-10 Last updated: 2020-01-20Bibliographically approved
Houben, A., Pien, N., Lu, X., Bisi, F., Van Hoorick, J., Boone, M. N., . . . Van Vlierberghe, S. (2016). Indirect Solid Freeform Fabrication of an Initiator-Free Photocrosslinkable Hydrogel Precursor for the Creation of Porous Scaffolds. Macromolecular Bioscience, 16(12), 1883-1894
Open this publication in new window or tab >>Indirect Solid Freeform Fabrication of an Initiator-Free Photocrosslinkable Hydrogel Precursor for the Creation of Porous Scaffolds
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2016 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 16, no 12, p. 1883-1894Article in journal (Refereed) Published
Abstract [en]

In the present work, a photopolymerized urethane-based poly(ethylene glycol) hydrogel is applied as a porous scaffold material using indirect solid freeform fabrication (SFF). This approach combines the benefits of SFF with a large freedom in material selection and applicable concentration ranges. A sacrificial 3D poly(epsilon-caprolactone) structure is generated using fused deposition modeling and used as template to produce hydrogel scaffolds. By changing the template plotting parameters, the scaffold channel sizes vary from 280 to 360 m, and the strut diameters from 340 to 400 m. This enables the production of scaffolds with tunable mechanical properties, characterized by an average hardness ranging from 9 to 43 N and from 1 to 6 N for dry and hydrated scaffolds, respectively. Experiments using mouse calvaria preosteoblasts indicate that a gelatin methacrylamide coating of the scaffolds results in an increased cell adhesion and proliferation with improved cell morphology.

Keywords
biocompatibility, hydrogels, photopolymerization, solid freeform fabrication, tissue engineering
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-314049 (URN)10.1002/mabi.201600289 (DOI)000390804200013 ()
Available from: 2017-02-06 Created: 2017-01-26 Last updated: 2017-11-29Bibliographically approved
Kumar, S., Yan, J., Poon, J.-f., Singh, V. P., Lu, X., Ott, M. K., . . . Kumar, S. (2016). Multifunctional Antioxidants: Regenerable Radical-Trapping and Hydroperoxide-Decomposing Ebselenols. Angewandte Chemie International Edition, 55(11), 3729-3733
Open this publication in new window or tab >>Multifunctional Antioxidants: Regenerable Radical-Trapping and Hydroperoxide-Decomposing Ebselenols
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2016 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 55, no 11, p. 3729-3733Article in journal (Refereed) Published
Abstract [en]

Regenerable, multifunctional ebselenol antioxidants were prepared that could quench peroxyl radicals more efficiently than -tocopherol. These compounds act as better mimics of the glutathione peroxidase enzymes than ebselen. Production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in human mononuclear cells was considerably decreased upon exposure to the organoselenium compounds. At a concentration of 25m, the ebselenol derivatives showed minimal toxicity in pre-osteoblast MC3T3cells.

National Category
Natural Sciences Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-280006 (URN)10.1002/anie.201510947 (DOI)000371521000034 ()26879742 (PubMedID)
Funder
Swedish Research CouncilCarl Tryggers foundation , 13:346, 13:120
Available from: 2016-03-07 Created: 2016-03-07 Last updated: 2017-11-30Bibliographically approved
Singh, V. P., Poon, J.-f., Butcher, R. J., Lu, X., Mestres, G., Karlsson Ott, M. & Engman, L. (2015). Effect of a Bromo Substituent on the Glutathione Peroxidase Activity of a Pyridoxine-like Diselenide. The Journal of Organic Chemistry, 50(15), 7385-7395
Open this publication in new window or tab >>Effect of a Bromo Substituent on the Glutathione Peroxidase Activity of a Pyridoxine-like Diselenide
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2015 (English)In: The Journal of Organic Chemistry, Vol. 50, no 15, p. 7385-7395Article in journal (Refereed) Published
Abstract [en]

In search for better mimics of the glutathioneperoxidase enzymes, pyridoxine-like diselenides 6 and 11,carrying a 6-bromo substituent, were prepared. Reaction of2,6-dibromo-3-pyridinol 5 with sodium diselenide provided 6via aromatic nucleophilic substitution of the 2-bromosubstituent. LiAlH4 caused reduction of all four ester groupsand returned 11 after acidic workup. The X-ray structure of 6showed that the dipyridyl diselenide moiety was kept in analmost planar, transoid conformation. According to NBOanalysis,this was due to weak intramolecular Se···O (1.1 kcal/mol) and Se···N-interactions (2.5 kcal/mol). That the 6-bromo substituent increased the positive charge on seleniumwas confirmed by NPA-analysis and seen in calculated andobserved 77Se NMR-shifts. Diselenide 6 showed a more than 3-fold higher reactivity than the corresponding des-bromocompound 3a and ebselen when evaluated in the coupled reductase assay. Experiments followed for longer time (2 h) confirmedthat diselenide 6 is a better GPx-catalyst than 11. On the basis of 77Se-NMR experiments, a catalytic mechanism for diselenide 6was proposed involving selenol, selenosulfide and seleninic acid intermediates. At low concentration (10 μM) where it showedonly minimal toxicity, it could scavenge ROS produced by MNC- and PMNC-cells more efficiently than Trolox.

National Category
Chemical Sciences Engineering and Technology
Research subject
Chemistry with specialization in Organic Chemistry; Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-259460 (URN)10.1021/acs.joc.5b00797 (DOI)000359393500007 ()
Funder
Swedish Research CouncilCarl Tryggers foundation , CTS 13:120 13:346
Available from: 2015-08-04 Created: 2015-08-04 Last updated: 2015-09-22Bibliographically approved
Lu, X., Mestres, G., Effati, P., Singh, V., Poon, J. & Karlsson Ott, M. (2015). Novel selenium- and tellurium-based antioxidants as modulators of inflammatory response. Paper presented at 8th Annual meeting of the Scandinavian Society for Biomaterials, Sigulda, Latvia, 6-8th of May 2015. European Cells and Materials, 29(Supp.1), 33-33
Open this publication in new window or tab >>Novel selenium- and tellurium-based antioxidants as modulators of inflammatory response
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2015 (English)In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 29, no Supp.1, p. 33-33Article in journal, Meeting abstract (Refereed) Published
National Category
Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-259462 (URN)
Conference
8th Annual meeting of the Scandinavian Society for Biomaterials, Sigulda, Latvia, 6-8th of May 2015
Available from: 2015-08-04 Created: 2015-08-04 Last updated: 2017-12-04Bibliographically approved
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