Sirolimus loaded chitosan functionalized PLGA nanoparticles protect against sodium iodate-induced retinal degeneration

Age-related macular degeneration (AMD) is a major health concern in the ageing human population. Though existing therapeutics have shown some efficacy, low retinal bioavailability of drugs continues to be a hindrance in ocular drug delivery system. Sirolimus (SIR) is one such drug. In this study, we developed chitosan functionalized PLGA nanoparticles (NP), (<300 nm), for effective and sustained SIR delivery to retina via single subconjunctival injection. Confocal laser microscopy demonstrated superiority of NP for delivering the model cargo, Rhodamine-B, to the posterior segment of eye as opposed to plain dye owing to bioadhesive and permeation enhancer property of chitosan coat. Further, we investigated the protective effect of sirolimus loaded chitosan functionalized PLGA nanoparticles (SIR-NP) vs plain sirolimus suspension (SIR) against sodium iodate-induced retinal degeneration model. Results revealed that SIR-NP enhanced the delivery of SIR in retina and significantly attenuated inflammatory and structural changes in comparison to plain SIR. SIR-NP more efficiently prevented outer nuclear layer thinning and photoreceptor degeneration post sodium iodate-induced toxicity. Moreover, SIR-NP upregulated the levels of anti-oxidants, induced autophagy and inhibited apoptosis in the damaged retina over a period of 21 days which was not seen with plain SIR. Also, no toxic effects on blood, liver or kidney were observed with SIR-NP treatment. Thus, SIR-NP could be a potential strategy to target AMD.

留言 (0)

沒有登入
gif