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Res."],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Allergic conjunctivitis (AC) is the most common inflammatory disease affecting the eye's ocular surface, lid, conjunctiva, and cornea. However, effective ocular drug delivery remains challenging due to physiological barriers such as the corneal barrier. Ketotifen (KF), a widely used antihistamine and mast cell stabilizer, for treating AC and atopic asthma but belongs to the Biopharmaceutical Classification System (BCS II) have poor solubility. This study developed a multiple strategies approach for the first time, utilizing the spanlastics nano-vesicular carriers\u2019 system (SP) containing KF using an ethanol injection method. The optimized KF-SP exhibited the smallest particle size, largest zeta-potential and entrapment efficiency \u223c232.5\u2009\u00b1\u20091.9\u00a0nm, -28\u2009\u00b1\u20090.51 and 73\u2009\u00b1\u20090.02%, respectively were further incorporated into PVA\/PVP polymeric dissolving microneedles (MNs) by using a micromolding technique. Scanning electron microscopy (SEM) analysis confirmed well-defined tips and morphology, and in vitro studies showed a controlled 93% cumulative release over 72\u00a0h, with a zero-order kinetic release profile, providing stable therapeutic levels. Pharmacodynamic evaluation using the Ovalbumin\/Aluminium hydroxide-induced AC model demonstrated significant reductions in IgE, TNF-\u03b1, and IL-6 levels by 68.7%, 71.3%, and 67.6%, respectively, while TGF-\u03b2 and IL-10 levels increased by 70.1% and 62.7% using ELISA (Enzyme-Linked Immunosorbent Assay). Gene expression analysis (IGF-1, Annexin A1, and Bcl2) further supported the therapeutic potential of this system. In this study, we proved the topical application of the multiple strategies approach KF-SP loaded PVA\/PVP MNs patch offers a targeted, sustained release treatment for AC, with promising implications for prolonged ocular therapy.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s13346-025-01796-x","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T13:23:26Z","timestamp":1739280206000},"page":"3161-3184","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Nano-spanlastics-loaded dissolving microneedle patches for ketotifen fumarate: advanced strategies for allergic conjunctivitis treatment and molecular insights"],"prefix":"10.1007","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-2288","authenticated-orcid":false,"given":"Sammar Fathy","family":"Elhabal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Nabarawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Fathi Mohamed","family":"Elrefai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud H.","family":"Teaima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai S.","family":"Shoela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gehad M.","family":"Khamis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Mohsen","family":"Faheem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada ahmed","family":"kholeif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud Tarek","family":"Sanad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"1796_CR1","doi-asserted-by":"crossref","unstructured":"Mu D, Zhou L, Shi L, Liu T, Guo Y, Chen H, et al. 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