期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 513, 期 1-2, 页码 238-246出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2016.09.013
关键词
Rapamycin micelles; Ocular inflammation; In vivo; Intravitreal injection
资金
- National Natural Science Foundation of China [51303136, 31671022]
- Key Program for International S&T Cooperation Projects of China [2015DFA50310]
- National Science and Technology Major Project [2014ZX09303301]
- Science and Technology Bureau of Wenzhou City [Y20140703, Y20140141]
The therapeutic efficacy of rapamycin conjugated monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone) (MPEG-PCL) micelles (rapamycin micelles) was evaluated in a rat experimental autoimmune uveitis (EAU) model. Rapamycin micelles exhibited spherical morphology and had a mean particle size of 40 nm and a zeta-potential of -0.89 mv. The water solubility of rapamycin improved by more than 1000-fold in a micellar formulation. Intravitreal injection of MPEG-PCL micelles did not result in vitreous hemorrhage or retinal detachment. Fluorescence microscopy demonstrated that labeled micelles localized to the retinal pigment epithelium for at least 14 days following injection and the drug concentration of rapamycin micelles in the retinal tissue was significantly higher than unconjugated rapamycin over this period. At the optimal concentration of rapamycin micelles (9 mu g/eye), clinical signs of EAU were abolished via the downregulation of the Th1 and Th17 response. There were no significant difference in T cell proliferation and delayed-type hypersensitivity between the treatment and control groups, suggesting that the therapeutic effect of rapamycin manifested locally in the eye and not systemically. These results indicate that intravitreal injection of rapamycin micelles is a promising therapy for controlling sterile intraocular inflammation. (C) 2016 Elsevier B.V. All rights reserved.
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