{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:21:07Z","timestamp":1784917267117,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T00:00:00Z","timestamp":1613174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Bevacizumab (BVZ), a recombinant humanized monoclonal antibody, has recently been proposed as a topical application in the treatment of anterior segment neovascularization; however, as there are some disadvantages in the administration of common eye-drops, ophthalmic topical drug delivery systems are under study to improve the precorneal residence time, reducing the frequency of administration. In this work, oil-in-water and water-in-oil BVZ-loaded microemulsions are developed, able to increase their viscosity, either by the formation of a liquid-crystalline structure upon aqueous dilution, thanks to the presence of Epikuron\u00ae 200 and polysorbate 80, or by body-temperature-induced jellification for the presence of Pluronic\u00ae F127 aqueous solution as an external phase. In oil-in-water microemulsion, hydrophobic ion pairs of BVZ were also prepared, and their incorporation was determined by release studies. Microemulsions were characterized for rheological behavior, corneal opacity, in vitro corneal permeation, and adhesion properties. The studied microemulsions were able to incorporate BVZ (from 1.25 to 1.6 mg\/mL), which maintained dose-dependent activity on retinal pigment epithelial ARPE-19 cell lines. BVZ loaded in microemulsions permeated the excised cornea easier (0.76\u20131.56% BVZ diffused, 4\u201320% BVZ accumulated) than BVZ commercial solution (0.4% BVZ diffused, 5% accumulated) and only a mild irritation effect on the excised cornea was observed. The good adhesion properties as well the increased viscosity after application, under conditions that mimic the corneal environment (from 1 \u00d7 103 to more than 100 \u00d7 103 mPa\u00b7s), might prolong precorneal residence time, proving these systems could be excellent topical BVZ release systems.<\/jats:p>","DOI":"10.3390\/pharmaceutics13020258","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T05:54:49Z","timestamp":1613282089000},"page":"258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Assessment of In-Situ Gelling Microemulsion Systems upon Temperature and Dilution Condition for Corneal Delivery of Bevacizumab"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8017-4956","authenticated-orcid":false,"given":"Elena","family":"Peira","sequence":"first","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2824-4309","authenticated-orcid":false,"given":"Giulia","family":"Chindamo","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4615-5812","authenticated-orcid":false,"given":"Daniela","family":"Chirio","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5335-8442","authenticated-orcid":false,"given":"Simona","family":"Sapino","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Oliaro-Bosso","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Rebba","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Interdepartmental Nanostructured Interfaces and Surfaces (NIS) Centre, University of Turin, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2280-0773","authenticated-orcid":false,"given":"Pavlo","family":"Ivanchenko","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Interdepartmental Nanostructured Interfaces and Surfaces (NIS) Centre, University of Turin, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Gallarate","sequence":"additional","affiliation":[{"name":"Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1634\/theoncologist.9-suppl_1-2","article-title":"Vascular endothelial growth factor as a target for anticancer therapy","volume":"9","author":"Ferrara","year":"2004","journal-title":"Oncologist"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1007\/s40265-014-0302-9","article-title":"Bevacizumab: A Review of Its Use in Advanced Cancer","volume":"74","author":"Keating","year":"2014","journal-title":"Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1056\/NEJM199412013312203","article-title":"Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders","volume":"331","author":"Aiello","year":"1994","journal-title":"N. 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