CONTROLLED INTRAOCULAR DELIVERY OF GANCICLOVIR WITH USE OF BIODEGRADABLE SCLERAL IMPLANT IN RABBITS

We evaluated biodegradable scleral implants as a controlled intraocula r delivery system of ganciclovir (GCV) for the treatment of cytomegalo virus retinitis in rabbits. The scleral implants (weight, 8.5 mg; leng th, 5 mm) were made of poly(DL-lactide) (PLA) or poly (DL-lactide-co-g lycolide) (PLGA) and contained various amounts of GCV. The in vitro re lease studies demonstrated a triphasic release pattern. The 10% GCV-lo aded 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 concentrati on in the range of ED(50) for human CMV was maintained in the vitreous for over 3 months and in the retina/choroid for over 5 months. The GC V concentration was greater in the retina/choroid than in the vitreous throughout the study. The scleral implants showed two phases of biode gradation: lagtime and erosion. In the erosion phase, the weight of PL GA dropped remarkably. All the scleral implants were separated into tw o pieces at the site of scleral penetration and displaced into the vit reous 10 weeks after implantation. The fragments disappeared from the vitreous and the subconjunctival space 5 months after implantation. Ou r findings suggest that the biodegradable scleral implant may be a pro mising device for the intraocular drug delivery of GCV.