محمود بارانی

Objective This study aimed to develop and evaluate ginsenoside Rg3 (GRg3)-loaded alginate/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) as an oral drug delivery system with improved anticancer and antioxidant potential. Significance Despite its pharmacological promise, GRg3 suffers from poor solubility, instability, and low oral bioavailability. Encapsulation in biopolymeric NPs may overcome these barriers by enhancing stability and providing controlled release. Methods GRg3-loaded alginate/PLGA NPs were synthesized and characterized for size, stability, rheology, and release kinetics. Antiproliferative activity, cell cycle effects, and apoptosis markers were assessed in PC-3 prostate cancer cells. In vivo safety and antioxidant effects were evaluated in healthy rats using biochemical assays and histopathological analysis of liver and kidney tissues. Results The NPs had a mean diameter of ∼200 nm with shear-thinning behavior. GRg3 release followed a sustained pattern, best fitting the Korsmeyer–Peppas model with anomalous transport. In vitro, the formulation inhibited PC-3 cell proliferation in a concentration- and time-dependent manner, induced G0–G1 arrest, and elevated caspase-3 activity within 6 h. In vivo, oral administration caused no significant hepatic or renal alterations, and histopathology showed no inflammation or necrosis. GRg3 also reduced malondialdehyde levels, confirming antioxidant activity. Conclusions Encapsulation of GRg3 in alginate/PLGA NPs enhanced its stability, anticancer activity, and antioxidant potential without systemic toxicity. These findings highlight the promise of GRg3-loaded nanocarriers for cancer therapy, warranting further evaluation in disease-specific models.