Juglone Encapsulation in PLGA Nanoparticles Improves Solubility and Enhances Apoptosis in HeLa Cells

The anticancer potential of juglone, a naphthoquinone derived from walnut trees, has been extensively studied; however, its hydrophobicity and toxicity obstruct its therapeutic applications. This study aimed to overcome these challenges by encapsulating juglone into poly (lactic-co-glycolic acid) (PLGA) nanoparticles and evaluating their antiproliferative and apoptotic effects on HeLa cells. Juglone nanoparticles (JNP) were obtained by single emulsion solvent evaporation method. Its key physicochemical properties, such as particle size, zeta potential, drug loading, release yield, and encapsulation efficiency values were calculated as 207.45 ± 1.67 nm, -24.12 ± 2.21 mV, 47.80, 66.90 and 90.12%, respectively. JNP's antiproliferative effects were compared to those of free juglone on HeLa cells. The calculated IC₅₀ values for free juglone and JNPs were 17.07 µM and 20.64 µM, respectively. Both formulations exhibited comparable dose-dependent antiproliferative effects across the tested concentrations. However, the nanoparticle-based delivery system demonstrated enhanced apoptotic activity, as evidenced by increased caspase-3 activation and greater suppression of BCL-2 levels relative to free juglone. These findings were further corroborated by TUNEL and immunocytochemical analyses, which confirmed the superior apoptotic induction by the nanosystem. Collectively, the results highlight the potential advantages of PLGA-based nanoparticle systems for the delivery of juglone, thereby improving its water solubility-a key limiting factor for its use-while minimizing its toxicity. These findings offer a promising approach for its application as an effective anticancer agent via nanoparticle-based delivery.