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dc.contributor.authorRobert, Marie-Claudeen_US
dc.contributor.authorFrenette, Mathieuen_US
dc.contributor.authorZhou, Chengxinen_US
dc.contributor.authorYan, Yueranen_US
dc.contributor.authorChodosh, Jamesen_US
dc.contributor.authorJakobiec, Frederick A.en_US
dc.contributor.authorStagner, Anna M.en_US
dc.contributor.authorVavvas, Demetriosen_US
dc.contributor.authorDohlman, Claes H.en_US
dc.contributor.authorPaschalis, Eleftherios I.en_US
dc.date.accessioned2016-04-01T15:48:20Z
dc.date.issued2016en_US
dc.identifier.citationRobert, Marie-Claude, Mathieu Frenette, Chengxin Zhou, Yueran Yan, James Chodosh, Frederick A. Jakobiec, Anna M. Stagner, Demetrios Vavvas, Claes H. Dohlman, and Eleftherios I. Paschalis. 2016. “A Drug Delivery System for Administration of Anti–TNF-α Antibody.” Translational Vision Science & Technology 5 (2): 11. doi:10.1167/tvst.5.2.11. http://dx.doi.org/10.1167/tvst.5.2.11.en
dc.identifier.issn2164-2591en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:26318687
dc.description.abstractPurpose To describe the fabrication, evaluation, and preliminary in vivo safety of a new drug delivery system (DDS) for topical anti–TNF-α antibody administration. Methods: A DDS was fabricated using inverse template fabrication of a hydrophobic three-dimensional porous scaffold (100–300 μm in diameter porosity) loaded with 10% polyvinyl alcohol hydrogel carrying 5 mg/ml (weight/volume) of anti–TNF-α antibody. Drug-loaded DDS was sterilized with 25 kGy of gamma irradiation. Long-term in vitro antibody affinity and release was evaluated at room temperature or 37°C using enzyme-linked immunosorbent assay (ELISA) and protein fluorescence. In vivo clinical and histolopathological assessment was performed by subcutaneous implantation in BALB/c mice for 3 months. Results: Gamma irradiation, repeated dry/wet cycles, and storage at room temperature for 1 year or 37°C for 1 month had no deleterious effects on antibody affinity. Anti–TNF-α release was high during the first minutes of aqueous exposure, followed by stabilization and gradual, low-dose, antibody release over the next 30 days. Histopathologic evaluation of explanted DDS showed a fibrous pseudocapsule and a myxoid acute/chronic inflammation without granuloma formation surrounding the implants. Conclusions: Sustained local delivery of anti–TNF-α antibody is feasible using the described DDS, which provides stability of the enclosed antibody for up to 1 year of storage. Preliminary results show good in vivo tolerance following subcutaneous placement for 3 months. The proposed fabrication and sterilization process opens new possibilities for the delivery of biologic agents to the anterior surface of the eye. Translational Relevance The described DDS will facilitate the treatment of ocular surface diseases amenable to biologic therapy.en
dc.language.isoen_USen
dc.publisherThe Association for Research in Vision and Ophthalmologyen
dc.relation.isversionofdoi:10.1167/tvst.5.2.11en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790433/pdf/en
dash.licenseLAAen_US
dc.subjectpolydimethylsiloxaneen
dc.subjecttumor necrosis factor alphaen
dc.subjectdrug delivery systemen
dc.subjectbiologicsen
dc.subjectsustained-releaseen
dc.subjectburnen
dc.titleA Drug Delivery System for Administration of Anti–TNF-α Antibodyen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalTranslational Vision Science & Technologyen
dash.depositing.authorZhou, Chengxinen_US
dc.date.available2016-04-01T15:48:20Z
dc.identifier.doi10.1167/tvst.5.2.11*
dash.contributor.affiliatedStagner, Anna M.
dash.contributor.affiliatedZhou, Chengxin
dash.contributor.affiliatedDohlman, Claes
dash.contributor.affiliatedChodosh, James
dash.contributor.affiliatedVavvas, Demetrios


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