title: Fabrication, implantation, elution, and retrieval of a steroid-loaded polycaprolactone subretinal implant.
abstract: A subretinal drug delivery system was developed to overcome the limitations of current treatments for retinal disease. A rod-shaped implant was made by embedding the corticosteroid triamcinolone acetonide within a biodegradable polycaprolactone polymer matrix. The implant was fabricated by homogeneously mixing the polymer and drug in solvent. The mixture was then dried, melted, and extruded, and the prepared solid form was drawn into a filament. The rods were mechanically sectioned to a length of 2 mm with a diameter of up to 320 microm. The rods were successfully implanted into the subretinal space of six rabbits. No complications were observed during the 4-week follow-up period. Initial observations of the implantation and elution characteristics revealed that polycaprolactone is well tolerated by the retinal tissue and that the implant can elute steroid for a period of at least 4 weeks without eliciting inflammatory response or complications. In vitro drug elution rates of different polymer to drug ratios and geometries into a balanced salt solution/bovine serum albumin (1%) solution showed an early rapid-release phase and late first-order phase. Histology and device retrieval after implantation revealed minimal encapsulation and good preservation of cellular morphology during the follow-up period and a more fibrous polymer microstructure of the implant.
authors.affiliation: Doheny Retina Institute, Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, 1450 San Pablo Street, Los Angeles, CA 90033, USA.
authors.forename: Nathan R F
authors.initials: NR
authors.lastname: Beeley
authors.forename: Juliana V
authors.initials: JV
authors.lastname: Rossi
authors.forename: Paulo A A
authors.initials: PA
authors.lastname: Mello-Filho
authors.forename: Mahmoud I
authors.initials: MI
authors.lastname: Mahmoud
authors.forename: Gildo Y
authors.initials: GY
authors.lastname: Fujii
authors.forename: Eugene
authors.initials: E
authors.lastname: de Juan
authors.forename: Signe E
authors.initials: SE
authors.lastname: Varner
mesh_terms: D020341:Absorbable Implants; D000792:Angiography / Q000379:methods; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001672:Biocompatible Materials; D049109:Cell Proliferation; D002829:Choroid / Q000378:metabolism; D016503:Drug Delivery Systems; D004343:Drug Implants; D009389:Neovascularization, Pathologic; D011091:Polyesters / Q000737:chemistry* / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry; D019736:Prostheses and Implants; D019919:Prosthesis Implantation; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013256:Steroids / Q000008:administration & dosage* / Q000737:chemistry; D013997:Time Factors; D014221:Triamcinolone / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D004343:Drug Implants; D011091:Polyesters; D011108:Polymers; D013256:Steroids; D014221:Triamcinolone; C016240:polycaprolactone; D012710:Serum Albumin, Bovine