Controlled delivery of ganciclovir to the retina with drug-loaded Poly(d,L-lactide-co-glycolide) (PLGA) microspheres dispersed in PLGA-PEG-PLGA Gel: a novel intravitreal delivery system for the treatment of cytomegalovirus retinitis.

Purpose: The aim of this study was to develop a formulation for intravitreal delivery by dispersing ganciclovir (GCV)-loaded Poly(d,L-lactide-co-glycolide (PLGA) microspheres in thermogelling PLGA-PEG-PLGA gel and to study the mechanism of drug-release characteristics both in vitro and in vivo. Methods: PLGA microspheres of GCV were prepared by the solvent evaporation method from Resomer RG 502H (D,L-lactide:glycolide::50:50; Mw, 8000 Da) and a 1:3 polymer blend of Resomer RG 502H and PLGA 6535 (D,L-lactide:glycolide::65:35; Mw, 45,000–75,000 Da). The prepared microspheres were dispersed uniformly and as a mixture (1:1) in 23% w/w of PLGA-PEG-PLGA aqueous gel solutions. GCV release in the aqueous medium was studied in vitro. A conscious rabbit microdialysis model with permanently implanted probes was selected as the method for investigating the vitreous GCV levels following an intravitreal administration of the formulation. Results: The formulation prepared, by a physical mixture of microspheres, was prep...