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Long-acting acid-sensitive ketal-linked dexamethasone microcrystals for treating experimental autoimmune uveitis

Corticosteroids have for some time been used as first-line drugs for the topical treatment of noninfectious uveitis, but poor ocular bioavailability and the rapid clearance of eye drops necessitate frequent dosing, reducing patient compliance. In this study, we used an acid-sensitive stearoxyl-ketal...

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Autores principales: Cai, Maoyu, Xu, Zunkai, Zhou, Xueyan, Li, Liangpin, Hua, Xia, Guo, Shutao, Yuan, Xiaoyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AIP Publishing LLC 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612960/
https://www.ncbi.nlm.nih.gov/pubmed/36313265
http://dx.doi.org/10.1063/5.0118311
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author Cai, Maoyu
Xu, Zunkai
Zhou, Xueyan
Li, Liangpin
Hua, Xia
Guo, Shutao
Yuan, Xiaoyong
author_facet Cai, Maoyu
Xu, Zunkai
Zhou, Xueyan
Li, Liangpin
Hua, Xia
Guo, Shutao
Yuan, Xiaoyong
author_sort Cai, Maoyu
collection PubMed
description Corticosteroids have for some time been used as first-line drugs for the topical treatment of noninfectious uveitis, but poor ocular bioavailability and the rapid clearance of eye drops necessitate frequent dosing, reducing patient compliance. In this study, we used an acid-sensitive stearoxyl-ketal-dexamethasone pro-drug microcrystals (SKD MCs), which is consistently safe and effective in the control of uveitis inflammation in rats. We used a rat model of experimental autoimmune uveitis (EAU) to evaluate the effects of SKD MCs in terms of clinical manifestations, molecular biology, pathological histology, and visual electrophysiology compared to dexamethasone sodium phosphate injection or phosphate-buffered saline. SKD MCs significantly reduced inflammation in EAU, improved the ability to suppress inflammatory cytokines and to protect retinal function, and significantly reduced retinal microglia activation, with no increase in intraocular pressure throughout the treatment. Our results indicate that the SKD MCs formulation holds promise as a new strategy for the treatment of noninfectious uveitis and potentially other ocular inflammatory diseases.
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spelling pubmed-96129602022-10-28 Long-acting acid-sensitive ketal-linked dexamethasone microcrystals for treating experimental autoimmune uveitis Cai, Maoyu Xu, Zunkai Zhou, Xueyan Li, Liangpin Hua, Xia Guo, Shutao Yuan, Xiaoyong APL Bioeng Articles Corticosteroids have for some time been used as first-line drugs for the topical treatment of noninfectious uveitis, but poor ocular bioavailability and the rapid clearance of eye drops necessitate frequent dosing, reducing patient compliance. In this study, we used an acid-sensitive stearoxyl-ketal-dexamethasone pro-drug microcrystals (SKD MCs), which is consistently safe and effective in the control of uveitis inflammation in rats. We used a rat model of experimental autoimmune uveitis (EAU) to evaluate the effects of SKD MCs in terms of clinical manifestations, molecular biology, pathological histology, and visual electrophysiology compared to dexamethasone sodium phosphate injection or phosphate-buffered saline. SKD MCs significantly reduced inflammation in EAU, improved the ability to suppress inflammatory cytokines and to protect retinal function, and significantly reduced retinal microglia activation, with no increase in intraocular pressure throughout the treatment. Our results indicate that the SKD MCs formulation holds promise as a new strategy for the treatment of noninfectious uveitis and potentially other ocular inflammatory diseases. AIP Publishing LLC 2022-10-26 /pmc/articles/PMC9612960/ /pubmed/36313265 http://dx.doi.org/10.1063/5.0118311 Text en © 2022 Author(s). https://creativecommons.org/licenses/by/4.0/All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Articles
Cai, Maoyu
Xu, Zunkai
Zhou, Xueyan
Li, Liangpin
Hua, Xia
Guo, Shutao
Yuan, Xiaoyong
Long-acting acid-sensitive ketal-linked dexamethasone microcrystals for treating experimental autoimmune uveitis
title Long-acting acid-sensitive ketal-linked dexamethasone microcrystals for treating experimental autoimmune uveitis
title_full Long-acting acid-sensitive ketal-linked dexamethasone microcrystals for treating experimental autoimmune uveitis
title_fullStr Long-acting acid-sensitive ketal-linked dexamethasone microcrystals for treating experimental autoimmune uveitis
title_full_unstemmed Long-acting acid-sensitive ketal-linked dexamethasone microcrystals for treating experimental autoimmune uveitis
title_short Long-acting acid-sensitive ketal-linked dexamethasone microcrystals for treating experimental autoimmune uveitis
title_sort long-acting acid-sensitive ketal-linked dexamethasone microcrystals for treating experimental autoimmune uveitis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612960/
https://www.ncbi.nlm.nih.gov/pubmed/36313265
http://dx.doi.org/10.1063/5.0118311
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