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However, MTX normally requires bi\u2010weekly intravitreal injections due to a short half\u2010life, causing rapid clearance below therapeutic thresholds within 72h. To overcome these limitations, sustained\u2010release carriers, including poly(lactic\u2010co\u2010glycolic) acid\u2010based implants, were investigated in vitro previously. These systems offer prolonged drug delivery but require relatively large\u2010gauge surgical implantation, which increases the risk of surgical complications and limits their practical use. In this study, MTX\u2010loaded liposomes that can be administered via a 30\u2010gauge cannula are developed, obviating the need for more invasive surgical implantation. This phospholipid\u2010based liposomal formulation succeeded in enabling sustained methotrexate release at therapeutic levels for over six weeks following a single intravitreal injection, demonstrated in vivo in a large animal pig model. High biocompatibility of this novel liposomal formulation is confirmed through longitudinal retinal structure (optical coherence tomography) and function (electroretinography) assessments. This liposomal formulation of MTX provides a clinically and surgically optimized drug delivery system that allows improved management of intraocular lymphoma and proliferative vitreoretinopathy in the future.<\/jats:p>","DOI":"10.1002\/adhm.202503230","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T06:58:20Z","timestamp":1758869900000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Methotrexate\u2010Loaded Liposomal Formulation Enables 6\u2010Week Sustained Intraocular Therapeutic Drug Release in a Porcine Model"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5496-2537","authenticated-orcid":false,"given":"Maximilian","family":"Hammer","sequence":"first","affiliation":[{"name":"David J Apple Laboratory for Vision Research and University Eye Clinic Heidelberg  69120 Heidelberg Germany"},{"name":"Faculty of Biosciences Heidelberg University 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