Enhanced cytotoxic activity of Moringa oleifera-loaded pharmacosomes against neuroblastoma

Moringa oleifera is known for its diverse therapeutic properties, including anticancer effects attributed to its rich phytochemical profile; yet, its poor solubility and stability limit its therapeutic translation. In this study, phospholipid-based pharmacosomal nanocarriers loaded with Moringa oleifera extract (MO) were developed and characterized to enhance its delivery and anticancer efficacy against neuroblastoma. Neuroblastoma is a common pediatric malignancy of neural crest origin with poor prognosis in high-risk cases, highlighting the need for safer and more effective therapeutic strategies. GC-MS analysis of the MO extract revealed diverse bioactive constituents with documented cytotoxic, pro-apoptotic, and antioxidant properties, including polyphenolic acids, flavonoid derivatives, nootkatone, uridine, and fatty acid derivatives. MO-loaded pharmacosomes (MO-PhS) formulated using lecithin and chitosan exhibited favorable physicochemical characteristics, including nanoscale size (41.07-190.12 nm), high entrapment efficiency (94.52 ± 2.79%), spherical morphology (PDI 0.29 ± 0.04), strong negative surface charge (-58.73 ± 0.99 mV), and enhanced thermal stability. In vitro cytotoxicity studies on SH-SY5Y neuroblastoma cells demonstrated a marked enhancement in anticancer activity for MO-PhS, achieving approximately a 10-fold reduction in IC₅₀ compared to free MO. Cell cycle analysis by flow cytometry revealed a pronounced redistribution of treated cells from G0/G1 into S and G2/M phases, indicating disruption of proliferative progression and replication stress, with pharmacosomal delivery of MO producing a more pronounced S-phase accumulation. Notably, these cell cycle perturbations were achieved at an approximately 10-fold lower concentration for MO-PhS compared to the free extract, underscoring the superior dose-efficiency of pharmacosomal delivery. Plain pharmacosomes exhibited minimal cytotoxicity against human normal fibroblasts (hFB), confirming carrier biocompatibility. These findings highlight MO-PhS as a promising nanoplatform for neuroblastoma therapy, offering enhanced cytotoxic efficacy, higher stability and antioxidant properties, and excellent biocompatibility, warranting further preclinical investigation.