Controlled intraocular delivery of ganciclovir with use of biodegradable scleral implant in rabbits

Abstract

We evaluated biodegradable scleral implants as a controlled intraocular delivery system of ganciclovir (GCV) for the treatment of cytomegalovirus retinitis in rabbits. The scleral implants (weight, 8.5 mg; length, 5 mm) were made of poly( dl-lactide) (PLA) or poly( dl-lactide-co-glycolide) (PLGA) and contained various amounts of GCV. The in vitro release studies demonstrated a triphasic release pattern. The 10% GCV-loaded scleral implant made from PLA with a molecular weight of 130 000 released GCV for 6 months. The in vivo release and biodegradation were studied using the 25% GCV-loaded implant made from PLGA( 75 25 ) with a molecular weight of 121 000 in pigmented rabbits. The GCV concentration in the range of ED 90 for human CMV was maintained in the vitreous for over 3 months and in the retina/choroid for over 5 months. The GCV concentration was greater in the retina/choroid than in the vitreous throughout the study. The scleral implants showed two phases of biodegradation: lagtime and erosion. In the erosion phase, the weight of PLGA dropped remarkably. All the scleral implants were separated into two pieces at the site of scleral penetration and displaced into the vitreous 10 weeks after implantation. The fragments disappeared from the vitreous and the subconjunctival space 5 months after implantation. Our findings suggest that the biodegradable scleral implant may be a promising device for the intraocular drug delivery of GCV.