Enhanced Cytotoxic Activity of Moringa oleifera–Loaded Pharmacosomes against Neuroblastoma

Abstract

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, excellent biocompatibility, warranting further preclinical investigation.