{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:53:56Z","timestamp":1775566436922,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia e Innovaci\u00f3n del Gobierno de Espa\u00f1a","award":["PID2022-142350OB-C22"],"award-info":[{"award-number":["PID2022-142350OB-C22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: While intravitreal administration allows for increased ocular exposure to anti-TNF-\u03b1 monoclonal antibodies, there is still a need for developing delivery systems able to prolong ocular drug exposure and alleviate patient compliance and safety concerns because of repeated injections. Therefore, the objective of this work was to guide the design of sustained-release formulations of anti-TNF-\u03b1 monoclonal antibodies for intravitreal administration through a model-based strategy in non-infectious uveitis in the preclinical setting. Methods: Using an in-house-developed anterior uveitis disease model in rats, an intravenous reference dose reducing free TNF-\u03b1 by 90% at the biophase was established. Intravitreal administrations of sustained-release formulations every 24 weeks were then simulated for adalimumab, golimumab and infliximab to evaluate TNF-\u03b1 kinetics in the anterior chamber of the eye at different release rates. The selected sustained-release formulation was further evaluated for possible formulation issues causing device emptying before the next administration. Results: Intravitreal administration of sustained-release formulations releasing adalimumab, golimumab or infliximab at 1.802, 0.979 and 1.442 \u03bcg\/week, respectively, met the predefined criteria of \u226590% reduction in free TNF-\u03b1 at the biophase. TNF-\u03b1 levels in aqueous humour were anticipated to be the most sensitive to detect possible formulation issues. Formulation emptying 10, 4 or 8 weeks for adalimumab, golimumab and infliximab, respectively, before next administration triggered TNF-\u03b1 reaching pathological levels at week 24 post-dose. Conclusions: This work underscores the potential of new approach methodologies in the preclinical drug development of sustained-release formulations for intravitreal administration in ocular inflammatory disorders with less animal testing and without compromising the accuracy of model-informed predictions for human translation.<\/jats:p>","DOI":"10.3390\/pharmaceutics18040445","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:11:28Z","timestamp":1775445088000},"page":"445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Model-Based Design of Sustained-Release Formulations of Anti-TNF-\u03b1 Monoclonal Antibodies for Intravitreal Administration"],"prefix":"10.3390","volume":"18","author":[{"given":"Javier","family":"Reig-L\u00f3pez","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain"},{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development, University of Valencia-Polytechnic University of Valencia, 46022 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Cuquerella-Gilabert","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain"},{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development, University of Valencia-Polytechnic University of Valencia, 46022 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4799-9076","authenticated-orcid":false,"given":"Javier","family":"Zarzoso-Foj","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain"},{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development, University of Valencia-Polytechnic University of Valencia, 46022 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3388-5023","authenticated-orcid":false,"given":"V\u00edctor","family":"Mangas-Sanju\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain"},{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development, University of Valencia-Polytechnic University of Valencia, 46022 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-4664","authenticated-orcid":false,"given":"Virginia","family":"Merino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain"},{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development, University of Valencia-Polytechnic University of Valencia, 46022 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4956-0247","authenticated-orcid":false,"given":"Matilde","family":"Merino-Sanju\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain"},{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development, University of Valencia-Polytechnic University of Valencia, 46022 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1185\/030079903125002847","article-title":"Tumour Necrosis Factor-Alpha Levels in Aqueous Humour and Serum from Patients with Uveitis: The Involvement of HLA-B27","volume":"20","year":"2004","journal-title":"Curr. 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