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The propamidine-isethionate (PI) 0.1% eye-drops are used in the treatment, but they have low-bioavailability due to precorneal loss parameters. In-situ-gels are administered as drops into the eye and changed into gel in the cul-de-sac, which may be able to solve these issues. In this study, we demonstrate different nano-ocular delivery-systems formulations of 0.1%PI loaded in-situ-gels using the ideas of pH &amp; temperature-stimulated in-situ-gelation. Pluronic F-127 a thermosensitive-polymer with chitosan as a pH-sensitive polymer that also enhances permeability was utilized as a gelling-agent. Several\u00a0\n                    <jats:italic>in-vitro<\/jats:italic>\n                    pharmaceutical and antiprotozoal assessments on\u00a0\n                    <jats:italic>Acanthamoeba keratitis\u00a0<\/jats:italic>\n                    were assessed for the developed formulations. It was observed that the created PI-chitosan nanoparticles in-situ-gel formulation showed smaller particle-size, higher zeta with a higher %inhibition of amoebae after 24-h incubation compared to other formulations with continuous drug release for 24-h. The PI-CSNPs in-situ-gel formulation offers an effective substitute for traditional BROLENE eye-drops in the management of\n                    <jats:italic>Acanthamebae<\/jats:italic>\n                    , around double the effect based on % amebae inhibition, reached 92%. It can reach the clinical-stage &amp; is appropriate for sustained-ocular-administration for the treatment of Acanthamoeba keratitis.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-03418-5","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T07:56:57Z","timestamp":1748937417000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Comparative evaluation of nano ocular delivery systems loaded pH and thermosensitive in situ gels for Acanthamoeba keratitis treatment"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6138-6320","authenticated-orcid":false,"given":"Basant A.","family":"Abou-Taleb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim A.","family":"Abdelwahab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"3418_CR1","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.2147\/OPTH.S301903","volume":"15","author":"MH Nasef","year":"2021","unstructured":"Nasef, M. 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