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 Liua, Qianni Wuc,Weirong Chenc, Haotian Linc, Yijun Liua, Huaqing Lianga, FangMing Zhuab
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.
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