[The inhibitive effects of 5-fluorouracil-loaded polylactic acid nanoparticles on human Tenon's capsule fibroblast in vitro].

Objective To investigate the inhibitive effects of 5-fluorouracil-loaded polylactic acid nanoparticles (5-FU-PLA-NPs)on human Tenon's capsule fibroblasts in vitro. Methods This paper was experimental study. MTT assay was performed to estimate the effects of 0.1 mg/L, 1.0 mg/L, 10.0 mg/L, 100.0 mg/L, 1000.0 mg/L unloaded polylactic acid nanoparticles(PLA-NPs) on fibroblasts proliferation on 48 h, 72 h. MTT assay was performed to estimate the effects of 0.1 mg/L, 1.0 mg/L, 10. 0 mg/L, 100.0 mg/L, 1000.0 mg/L original 5-FU and 5-FU-PLA-NPs on fibroblasts' proliferation on 7 consecutive days respectively. The inhibitory rate of the two drugs against the fibroblasts was calculated. Cells were exposed to 100 mg/L original 5-FU and 5-FU-PLA-NPs respectively for 7 days. Semi-quantitative RT-PCR was used to observe the mRNA expression of type Ⅲ procollagen at the 1st day, 5th day and 7th day. Results PLA-NPs had no cytotoxicity on the fibroblasts. Both 5-FU-PLA-NPs and original 5-FU could inhibit the proliferation of the fibroblasts and make the expression of type Ⅲ procollagen mRNA lower in dose-dependent and time-dependent manner. The inhibitive effect of original 5-FU was more effective than 5-FU-PLA-NPs in the initial period, but the inhibitive effect of 5-FU-PLA-NPs was more effective than original 5-FU in long time. Conclusion PLA has good biocompatibility and safety, and can be used as a carrier of ophthalmic drags. 5-FU-PLA-NPs shows slow-releasing function. 5-FU-PLA-NPs can be proposed as a potential controlled and targeted ophthalmic delivery system for the treatment of antifibrosis after glaucoma filtering surgery. (Chin J Ophthalmol, 2009,45:26-31) Key words: Fluorouracil;  Nano particles;  Polymers;  Lactic acid;  Fibroblasts;  Drug carriers