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Methotrexate-loaded liposomal formulation enables 6-week sustained intraocular therapeutic drug release in a porcine model

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...

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Main Authors: Hammer, Maximilian (Author) , Skrzypczyk, Lea (Author) , Wohlfart, Sabrina (Author) , Ackermann, Bryan Calder (Author) , Geisweid, Ludwig (Author) , Pohl, Simon William (Author) , Karaivanova, Margarita (Author) , Herth, Jonathan (Author) , Augustin, Victor A. (Author) , Studier-Fischer, Alexander (Author) , Sackmann, Tina (Author) , Kaulen, Leon D. (Author) , Steyer, Anna (Author) , Mier, Walter (Author) , Steel, David H. W. (Author) , Xue, Kanmin (Author) , Auffarth, Gerd U. (Author) , Uhl, Philipp (Author)
Format: Article (Journal)
Language:English
Published: 2025
In: Advanced healthcare materials
Year: 2025, Pages: 1-12
ISSN:2192-2659
DOI:10.1002/adhm.202503230
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/adhm.202503230
Verlag, kostenfrei, Volltext: http://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202503230
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Author Notes:Maximilian Hammer, Lea Skrzypczyk, Sabrina Wohlfart, Bryan Calder Ackermann, Ludwig Geisweid, Simon William Pohl, Margarita Karaivanova, Jonathan Herth, Victor Aristide Augustin, Alexander Studier-Fischer, Tina Sackmann, Leon Kaulen, Anna Steyer, Walter Mier, David H Steel, Kanmin Xue, Gerd Uwe Auffarth, and Philipp Uhl
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Summary: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.
Item Description:Erstmals veröffentlicht: 25. September 2025
Gesehen am 16.10.2025
Physical Description:Online Resource
ISSN:2192-2659
DOI:10.1002/adhm.202503230

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