| Objective:To test the best parameters for 5-fluorouracil polyactic acid microsphere preparation. To study its features, safety and the efficacy in prevention of proliferative vitreoretinopathy.Methods:The influences of different factors on average drug loading and average incorporation efficiency of microspheres were evaluated by orthogonal-designing method using L9(34) table. To observe 5-fluorouracil polyactic acid microsphere release features in vitro by shaking in stable temperature. After 60Co radiation, microsphere was implanted inside the dorsal skin of mice. The skin and the microsphere were observed after mice were sacrificed every other days. To implant microsphere into vitreous cavity of rabbits. Drug content in aqueous humor was measured regularly. Flash ERG was repeated on the 2nd,5th,9th and 14th day after implantation. Rats were sacrificed on the 28th day after implantation. Scanning and transmitted electrical microscope were used to evaluate the effect on cornea, chamber angle and retina of microsphere.48 healthy rabbits were divided into 3 groups:Group 1 is for 5-fluorouracil polyactic acid microsphere; Group 2 is for normal saline control group; Group 3 is for 5-fluorouracil control group. Macrophages were implanted into vitreous cavity of rabbit to form animal model of proliferative vitreoretinopathy.0.2ml BSS containing 25mg microsphere with 2.6mg 5-fluorouracil was injected into vitreous cavity of two eyes of Group 1.0.2ml BSS and 0.2ml BSS containing 0.5mg 5-fluorouracil were injected into vitreous cavity of Group 2 and 3, respectively. The efficacy was evaluated according to Ryan grade of proliferative vitreoretinopathy.Results:The micropheres with good fluidity and the surface morphology showed spherical particles with many little pores observed by EPMA. The average particle size was 80μm with 92.5% of the microspheres being in the range of 40-120μm. The average drug loading and the average incorporation efficiency were 10.44%,73.1% respectively. The cumulated drug release ratio is 72.3% as 5-fluorouracil polyactic acid microsphere released in vitro for 672hrs. It shows controlled release ability. Drug content and form characteristics showed no change after 60Co radiation. After 1 month since implantation inside mice skin, microsphere showed breaks and adherence with good histocompatibility. Drug content of aqueous humor measurement confirmed the controlled release characteristics. Drug concentration in vivo maintains high level. Its half life T1/2 is 379.05h. Latent and amplitude of ERG showed no change after implantation of microsphere into vitreous cavity. Histology and electrical microscope examination showed no change, too. Ratio of retinal detachment of Group 2 is 62.5% and 71.9% on the 21st and 28th day. Ratio of Group 3 is 56.3% and 68.8% whereas that of Group 1 is 12.5% and 12.5%. There is statistical difference between retinal detachment ratio of Group 1 and 2 or 3 confirmed with t test (P<0.01). There is no statistical difference between retinal detachment ratio of Group 2 and 3 (P>0.05).Conclusions:5-fluorouracil polyactic acid microsphere of this study possesses good controlled release characteristics.60Co radiation is an effective sterilization way. Drug content in vivo can keep high level for a long time. No prominent side effect or complication occurred after implantation into the vitreous cavity. Implantation of 5-fluorouracil polyactic acid microsphere into vitreous cavity can prevent proliferative vitreoretinopathy in animal model induced by macrophages effectively.5-fluorouracil polyactic acid microsphere will become an excellent way for prevention of proliferative vitreoretinopathy.
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