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methotrexate polymeric prodrug
- Development stage
- Preclinical
- Lead developer
- University of British Columbia
- Modality
- Small Molecules, Biodegradable Polymers → Polymer-based Nanoparticles → Nanoparticles → Drug Delivery Systems
- Administration
- Intravenous
01
Overview
Methotrexate polymeric prodrug (specifically folic acid-functionalized hyperbranched polyglycerol-methotrexate, HPG-FA-MTX) is a preclinical macromolecular prodrug designed for the targeted treatment of inflammatory joint diseases, such as rheumatoid arthritis. Developed by researchers at the University of British Columbia, the prodrug consists of the anti-rheumatic drug methotrexate (MTX) conjugated via ester linkages to a long-circulating, biocompatible hyperbranched polyglycerol (HPG) polymer, which is further functionalized with folic acid (FA) as a targeting ligand. This macromolecular design allows the prodrug to selectively accumulate in inflamed joints through the enhanced permeation and retention (EPR) effect and active folate receptor targeting. Once in the inflamed joint, MTX is gradually released over time via pH-dependent and enzymatic hydrolysis, particularly mediated by elevated levels of matrix metalloproteinases (MMPs) and esterases in the synovial fluid, thereby maximizing therapeutic efficacy while minimizing systemic toxicity.
- Other names
- HPG-FA-MTXHPG-MTXfolate-targeted hyperbranched polyglycerol-methotrexate prodrugfolic acid-functionalized hyperbranched polyglycerol-methotrexate
02
Targets
FOLR1 (FRα)FOLR2 (Folate receptor beta)
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