Development of Polyethylene Glycol-Modified Liposomes of Phenolic Glycoside 1 for Enhanced Anti-Aging Effect

Objective This study aimed to develop polyethylene glycol (PEG)-modified liposomes (PG-1-Ls) to overcome the poor oral bioavailability and burst release of phenolic glycoside 1 (PG-1), an anti-aging compound isolated from Moringa oleifera seeds. Methods PG-1-Ls were preparedby thin-film dispersion and optimized via a Box-Behnken design. The formulation wascharacterized for particle size, encapsulation efficiency (EE%), drug loading (DL%), andmorphology. Stability, in vitro release in four media, and safety in zebrafish were evaluated. Pharmacokinetics were studied in rats, and anti-aging efficacy was assessed in a D-galactose-induced zebrafish model by measuring β-galactosidase activity. Results The optimized PG-1-Lswere spherical and uniform (154.6 ± 3.8 nm), with high EE% (88.29%) and good stability. They successfully eliminated the initial burst release of PG-1, demonstrating sustained release profiles. In rats, PG-1-Ls increased the oral bioavailability (AUC) by 6.25-fold and the peak concentration(C~max~) by 3.9-fold compared to free PG-1. The formulation also showed improved safety in zebrafish. In the aging model, both PG-1 and PG-1-Ls significantly reduced β-galactosidaseactivity, with PG-1-Ls exhibiting superior efficacy comparable to the positive control. Conclusion PEGylated liposomes significantly enhance the sustained release, oral bioavailability, safety, and in vivo anti-aging activity of PG-1, representing a promising delivery system for its application. Graphical abstract