Subretinal drug delivery using polymeric matrix loaded filaments

Abstract

Abstract: : Purpose: To investigate the feasibility and initial safety of subretinal drug delivery using polymeric matrix loaded filaments in order to overcome the limitations of adverse systemic and intravitreal procedures along with diffusion limitations of larger (<70Kd) molecules. Methods: Matrix loaded filaments were implanted in the subretinal space of 6 rabbits. Drug–loaded filaments were comprised of the triamcinolone acetonide (TA) embedded within a bioerodible poly epsilon caprolactone (PCL) matrix. Drug loading was achieved by preparing a homogenous polymer–drug solvent solution that was subsequently dried and melt–extrusion–extended into shape. In vitro drug elution rate into a BSS/BSA (1%) solution was quantified by reverse phase HPLC. All rabbits underwent fluorescein angiography, fundus photography, OCT and ERG testing preoperatively and at 1, 2, 3 and 4 weeks after surgery. The follow–up period was 1 month. Four eyes underwent histology evaluation and 2 eyes underwent HPLC evaluation of the TA concentrations in the vitreous, retina, choroid, sclera and filament. Results: Filaments of length 2 mm by up to a diameter of 200 µm with an additional length of 0.1 mm for a 45° beveled point at the insert end were successfully implanted into the subretinal space of all 6 rabbits without complication. Fundus photography, fluorescein angiography, OCT, ERG and histology demonstrated that the filament remained positioned in the subretinal space for the follow–up period without adverse effects. In vitro studies showed that a TA distribution of 151.9 ± 29.5 ng was achieved in each filament via the melt–extrusion–extension process. In vitro drug elution rate into a BSS/BSA (1%) solution showed a TA drug release in two phases: an early rapid phase and late 1^st order phase. One month sustained release of TA with PCL was shown to be possible with detectable amounts of TA in the tissue surrounding the implant. Conclusions: Based upon this initial investigation, it appears that subretinal drug delivery using matrix–loaded filaments is feasible and well tolerated by the retina.

Keywords: retina • corticosteroids • pharmacology