ArticleJournal of biological engineering2026
Self-assembled PEGylated nanoparticles based on Elafibranor derivative 3d for the treatment of metabolic dysfunction-associated steatohepatitis.
Article in Journal of biological engineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND &
aimsTreatment of metabolic dysfunction-associated steatohepatitis (MASH) is constrained by the challenge of delivering highly hydrophobic drugs, whose poor water solubility severely hinders clinical application.
methodsA prodrug-based self-assembly strategy was employed. PEGylated 3d was synthesized via covalent conjugation of Elafibranor derivative 3d with Polyethylene glycol (PEG), and the amphiphilic conjugate spontaneously self-assembled into nanoparticles in aqueous solution without requiring exogenous polymers/lipids. The nanoparticles were characterized for size, morphology, and colloidal stability. In vitro lipid-lowering activity was assessed in an Free fatty acids (FFAs) -induced HepG2 model. In vivo efficacy was evaluated in a high-fat diet (HFD)-induced MASH mouse model following oral administration of PEGylated 3d nanoparticles (30 mg/kg, 3d-equivalent) compared to free 3d.
resultsPEGylated 3d self-assembled into stable spherical nanoparticles with a mean diameter of 255.3 ± 24.79 nm. In the MASH mouse model, PEGylated 3d (30 mg/kg) demonstrated significantly superior efficacy compared to free 3d: serum total cholesterol (TC) decreased by 34.3%, liver superoxide dismutase (SOD) activity increased by 35.6%, non-alcoholic fatty liver disease (NAFLD) activity score (NAS) score decreased by 62.3%, and liver lipid droplets reduced by 90.2%.
conclusionThe structure-guided PEGylated prodrug nanoassembly effectively overcomes the solubility limitation of hydrophobic MASH therapeutics and exhibits enhanced anti-steatotic and antioxidant effects through improved drug delivery. This work establishes a promising nanocarrier-free drug self-delivery paradigm for MASH treatment.
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