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.

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.