Experimental Inhibitory, and Pharmacokinetic Stydy on The Development of Proliferative Vitreoretinopathy by Sustained Delivery of Intravitreal Fluoropyrimidenes

ABSTRACT

The efficacy of the sustained release-delivery system was tested in suppressing the development of proliferative vitreoretinopathy(PVR) with intravitreal Fluoropyrimidines(5-Fu FU, Fluorouridine FUD, 5-Fluoro-5'-monophosphate FUMP). PVR was induced in one-hundred-eightyeight eyes of one-hundred-twenty rahbits by intravireal injection of homologous dermal fibroblasts(250.000 cells/0.1 ml). Each drugs were encapsulated with liposome(LFU. LFUD. LFUMP) or polymer(PFU. PFUD) and non-coated drugs wer e used as controls. 3 weeks after injections of fibroblasts, retina detached in 50.0% of control eyes. Among treated eyes, the detachment rates in percentage are as follows; FU 37.5, FUD 50.3, LFU 37.5, LFUD 37.5, PFU 16.7, PFUD 22.2. For the pharmacokinetic study. radiolaveled(-14C) drugs were used in liposome group and frozen vitreouses were measured by scintillatng counter; polymer group was measured by HPLC. The intravitreal half life(hour) of injected drugs were FU 3.2, FUMP 2.9, LFU 7.1, LFUMP 7.6, and PFU was exceptionally long(11.1 days).