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However, several drug and formulation challenges, such as poor drug solubility, short pre-corneal residence time, and poor patient compliance, have limited the ocular bioavailability of CsA to &lt;\u20095%. A CsA cyclodextrin-based ternary complex loaded dissolvable nano drug reservoir films were developed to overcome these limitations and efficiently manage DED. Drug-loaded nano-reservoir films were fabricated via lithography using silicone and poly (dimethyl siloxane) (PDMS) molds. Different physicochemical characterizations were performed to confirm the formation of stable CsA-cyclodextrin-based ternary complexes. Formation of nanoreservoirs on the films was confirmed using SEM and AFM. Optimized CsA-complex-loaded nano-reservoir films were evaluated for <jats:italic>in vitro<\/jats:italic> drug release, ex vivo corneal permeation, and <jats:italic>in vivo<\/jats:italic> precorneal retention. Preclinical efficacy studies were performed to assess the efficacy of CsA-complex-loaded nano-reservoirs in an experimental dry-eye mouse model. Physicochemical characterization confirmed the formation of a stable complex and the improved solubility of CsA. In vitro release and ex vivo permeation studies indicated a controlled drug release and improved permeation, respectively. Furthermore, tear volume measurement and corneal damage assessment using slit-lamp imaging suggested decreased dry eye symptoms, significantly increasing tear volume in the drug-loaded nano-reservoir-treated group. Moreover, histopathological studies corroborated the tear volume and slit-lamp imaging results, with reduced inflammation and neovascularization. The poorly water-soluble drug with cyclodextrin complex incorporated nanoreservoir films presents a potential alternative for managing various ocular diseases.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1208\/s12249-025-03104-9","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T15:09:42Z","timestamp":1744902582000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cyclosporine a Eluting Nano Drug Reservoir Film for the Management of Dry Eye Disease"],"prefix":"10.1208","volume":"26","author":[{"given":"Pinal","family":"Chaudhari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek M.","family":"Ghate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhavan","family":"Nampoothiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2884-0015","authenticated-orcid":false,"given":"Shaila A.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"3104_CR1","doi-asserted-by":"publisher","unstructured":"Agarwal P, Rupenthal ID. 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