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...

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Published in:Journal of drug delivery science and technology 2023-04, Vol.82, p.104369, Article 104369
Main Authors: Suri, Reshal, Nag, Tapas C., Mehra, Nikita, Neupane, Yub Raj, Shafi, Sadat, Sharma, Devyani, Sharma, Kalicharan, Sultana, Yasmin, Kohli, Kanchan
Format: Article
Language:English
Subjects:
Age-related macular degeneration
Chitosan
PLGA
Sirolimus
Sodium iodate
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cited_by cdi_FETCH-LOGICAL-c303t-36fa58715575c37e38b5f3ca800c4c88c1a200117f81c3a08f164b8d9ecbf1893
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container_title Journal of drug delivery science and technology
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creator Suri, Reshal
Nag, Tapas C.
Mehra, Nikita
Neupane, Yub Raj
Shafi, Sadat
Sharma, Devyani
Sharma, Kalicharan
Sultana, Yasmin
Kohli, Kanchan
description 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), (
doi_str_mv 10.1016/j.jddst.2023.104369
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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), (&lt;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. 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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. 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subjects Age-related macular degeneration
Chitosan
PLGA
Sirolimus
Sodium iodate
title Sirolimus loaded chitosan functionalized PLGA nanoparticles protect against sodium iodate-induced retinal degeneration
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