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文獻名：Tacrolimus-loaded methoxy poly(ethylene glycol)-block-poly(D,L)-lactic–co-glycolic acid micelles self-assembled in aqueous solution for treating cornea immune rejection after allogenic penetrating keratoplasty in rats 

 

作者：Dong Liu^a, Qianni Wu^c,Weirong Chen^c, Haotian Lin^c, Yijun Liu^a, Huaqing Liang^a, FangMing Zhu^ab 

^aGDHPPCLab, School of Chemistry, Sun Yat–Sen University, 510275, China

^bKey Lab for Polymer Composite and Functional Materials of Ministry of Education, School of Chemistry, Sun Yat–Sen University, Guangzhou 510275, China

^cState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China

 

摘要：This study aimed to develop a stable and biodegradable tacrolimus loaded nanocarrier that enhanced tacrolimus corneal penetration and delivered in a sustained manner, thus to create a promising treatment to prevent immune rejection after corneal allografts. Spherical tacrolimus loaded methoxy poly (ethylene glycol)-block-poly (D,L)-lactic-co-glycolic acid (mPEG-b-PLGA) micelles with a mean diameter of 81.3?±?1.3?nm were prepared by the solvent-evaporation-induced self-assembly. The physicochemical properties of tacrolimus loaded mPEG-b-PLGA micelles were evaluated, and the in vitro release behavior, degradation, cytotoxicity and bio-safety were all assessed. The ex vivo permeation of tacrolimus using rabbit corneas was also performed, and the cumulative permeation amount of tacrolimus from mPEG-b-PLGA micelles was significantly higher than 0.05% tacrolimus eye drops (p?<?0.05). These results indicated that the formulations were feasible for intraocular drug delivery. Compared with 0.05% tacrolimus eye drops, the in vivo immunofluorescence analysis indicated the tacrolimus loaded mPEG-b-PLGA micelles remarkably inhibit the immune rejection after corneal allograft, with the lower expression levels of nuclear factor of activated T cells (NFAT), cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8). In conclusion, we provided evidences that tacrolimus loaded mPEG-b-PLGA micelles would be a promising treatment for immune rejection after corneal transplantation.