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Methotrexate-Loaded Liposomal Formulation Enables 6-Week Sustained Intraocular Therapeutic Drug Release in a Porcine Model

Lookup NU author(s): Professor David SteelORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2025 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.Methotrexate (MTX) inhibits cell proliferation, which underlies ocular diseases, including intraocular lymphoma and proliferative vitreoretinopathy. However, MTX normally requires bi-weekly intravitreal injections due to a short half-life, causing rapid clearance below therapeutic thresholds within 72h. To overcome these limitations, sustained-release carriers, including poly(lactic-co-glycolic) acid-based implants, were investigated in vitro previously. These systems offer prolonged drug delivery but require relatively large-gauge surgical implantation, which increases the risk of surgical complications and limits their practical use. In this study, MTX-loaded liposomes that can be administered via a 30-gauge cannula are developed, obviating the need for more invasive surgical implantation. This phospholipid-based 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.

Publication metadata

Author(s): Hammer M, Skrzypczyk L, Wohlfart S, Ackermann BC, Geisweid L, Pohl SW, Karaivanova M, Herth J, Augustin VA, Studier-Fischer A, Sackmann T, Kaulen L, Steyer A, Mier W, Steel DH, Xue K, Auffarth GU, Uhl P

Publication type: Article

Publication status: Published

Journal: Advanced Healthcare Materials

Year: 2026

Volume: 15

Issue: 1

Print publication date: 09/01/2026

Online publication date: 25/09/2025

Acceptance date: 10/09/2025

Date deposited: 20/10/2025

ISSN (print): 2192-2640

ISSN (electronic): 2192-2659

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/adhm.202503230

DOI: 10.1002/adhm.202503230

Data Access Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

PubMed id: 40999813

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