title: A Drug Delivery System for Administration of Anti-TNF-α Antibody.
abstract: OBJECTIVE
  To describe the fabrication, evaluation, and preliminary in vivo safety of a new drug delivery system (DDS) for topical anti-TNF-αantibody 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-αantibody. 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-αrelease 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-αantibody 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.
  
  
  CONCLUSIONS
  The described DDS will facilitate the treatment of ocular surface diseases amenable to biologic therapy.
authors.affiliation: Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA ; Massachusetts Eye and Ear Infirmary/Schepens Eye Research Institute, Boston Keratoprosthesis Laboratory, Harvard Medical School, Boston, MA, USA.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Robert
authors.affiliation: Université du Québec à Montréal, Department of Chemistry, Montreal, QC, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Frenette
authors.affiliation: Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: Chengxin
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Angiogenesis Laboratory, Harvard Medical School, Boston, MA, USA.
authors.forename: Yueran
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Chodosh
authors.affiliation: Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA ; Massachusetts Eye and Ear Infirmary, David G. Cogan Laboratory of Ophthalmic Pathology, Harvard Medical School, Boston, MA, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Jakobiec
authors.affiliation: Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA ; Massachusetts Eye and Ear Infirmary, David G. Cogan Laboratory of Ophthalmic Pathology, Harvard Medical School, Boston, MA, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Stagner
authors.affiliation: Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Angiogenesis Laboratory, Harvard Medical School, Boston, MA, USA.
authors.forename: Demetrios
authors.initials: D
authors.lastname: Vavvas
authors.affiliation: Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA ; Massachusetts Eye and Ear Infirmary/Schepens Eye Research Institute, Boston Keratoprosthesis Laboratory, Harvard Medical School, Boston, MA, USA.
authors.forename: Claes H
authors.initials: CH
authors.lastname: Dohlman
authors.affiliation: Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA ; Massachusetts Eye and Ear Infirmary/Schepens Eye Research Institute, Boston Keratoprosthesis Laboratory, Harvard Medical School, Boston, MA, USA.
authors.forename: Eleftherios I
authors.initials: EI
authors.lastname: Paschalis
keywords: biologics; burn; drug delivery system; polydimethylsiloxane; sustained-release; tumor necrosis factor alpha