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文獻名： A novel FK506 loaded nanomicelles consisting of amino-terminated poly(ethylene glycol)-block-poly(D,L)-lactic acid and hydroxypropyl methylcellulose for ocular drug delivery

 

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

^aGDHPPC Lab, 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：FK506 (tacrolimus) is an effective immunosuppressant, but its poor water solubility and low bioavailability impose barriers to ocular drug delivery. The nanomicelles (NMs) formulations comprised of amino-terminated poly(ethylene glycol-block-poly(D,L)-lactic acid) (NH2-PEG-b-PLA) and hydroxypropyl methylcellulose (HPMC) were developed to increase the penetration of hydrophobic drugs in the eye and enhance the drug bioavailability for ocular disorder therapy. Spherical FK506/NH2-PEG-b-PLA/HPMC NMs with mean diameter of 101.4?±?1.3?nm were prepared by solvent-evaporation-induced self-assembly in aqueous solution. The NMs that sufficiently solubilized FK506 were evaluated in terms of stability, drug loading, encapsulation efficiency, surface tension, cellular cytotoxicity and in vitro release, and the results revealed the NMs were suitable for intraocular drug delivery. Compared with the 0.05% FK506 suspension drops, the in vitro permeation amount of FK506 from NMs exhibited significant increase. Besides, the higher concentration and longer retention of FK506 in ocular tissue were also confirmed in vivo. Furthermore, the FK506/NH2-PEG-b-PLA/HPMC NMs obviously inhibited the allograft rejection after corneal transplantation in rats. In conclusion, FK506/NH2-PEG-b-PLA/HPMC NMs formulations as a promising ocular drug delivery system would be able to improve the bioavailability and efficacy of FK506 in anti-allograft rejection.