1. Subconjunctival injection of rapamycin-loaded polymeric microparticles for effective suppression of noninfectious uveitis in rats.
- Author
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Mo L, Deng M, Chen J, Huai S, Du L, Xu X, Guo Q, Chen H, Li X, and Bao Z
- Subjects
- Animals, Rats, Inbred Lew, Rats, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents chemistry, Female, Drug Liberation, Delayed-Action Preparations, Microspheres, Disease Models, Animal, Drug Delivery Systems, Conjunctiva drug effects, Autoimmune Diseases drug therapy, Drug Carriers chemistry, Injections, Intraocular, Uveitis drug therapy, Sirolimus administration & dosage, Polyethylene Glycols chemistry, Polyethylene Glycols administration & dosage, Polyesters chemistry, Polyesters administration & dosage
- Abstract
Noninfective uveitis is a major cause of vision impairment, and corticosteroid medication is a mainstay clinical strategy that causes severe side effects. Rapamycin (RAPA), a potent immunomodulator, is a promising treatment for noninfective uveitis. However, because high and frequent dosages are required, it is a great challenge to implement its clinical translation for noninfective uveitis therapy owing to its serious toxicity. In the present study, we engineered an injectable microparticulate drug delivery system based on biodegradable block polymers (i.e., polycaprolactone-poly (ethylene glycol)-polycaprolactone, PCEC) for efficient ocular delivery of RAPA via a subconjunctival injection route and investigated its therapeutic efficacy in an experimental autoimmune uveitis (EAU) rat model. RAPA-PCEC microparticles were fabricated using the emulsion-evaporation method and thoroughly characterized using scanning electron microscopy, fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The formed microparticles exhibited slow in vitro degradation over 28 days, and provided both in vitro and in vivo sustained release of RAPA over 4 weeks. Additionally, a single subconjunctival injection of PCEC microparticles resulted in high ocular tolerance. More importantly, subconjunctival injection of RAPA-PCEC microparticles significantly attenuated the clinical signs of EAU in a dose-dependent manner by reducing inflammatory cell infiltration (i.e., CD45
+ cells and Th17 cells) and inhibiting microglial activation. Overall, this injectable microparticulate system may be promising vehicle for intraocular delivery of RAPA for the treatment of noninfective uveitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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