Intravitreal injection of rapamycin-loaded polymeric micelles for inhibition of ocular inflammation in rat model.
The therapeutic efficacy of rapamycin conjugated monomethoxy poly(ethylene glycol)-poly(ε-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 40nm and a zeta-potential of -0.89mv. 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 (9μg/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.
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, PR China.
Wei
W
Wu
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, PR China.
Zhifen
Z
He
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, PR China.
Zhaoliang
Z
Zhang
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, PR China.
Xinxin
X
Yu
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, PR China. Electronic address: szmeyes@126.com.
Zongming
Z
Song
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, PR China. Electronic address: lixingyi_1984@163.com.
Xingyi
X
Li
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002924:Ciliary Body / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D058449:Intravitreal Injections; D008823:Micelles; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014822:Vitreous Body / Q000378:metabolism
D016207:Cytokines; D007166:Immunosuppressive Agents; D008823:Micelles; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D020123:Sirolimus
In vivo; Intravitreal injection; Ocular inflammation; Rapamycin micelles