Document Type

Article

Publication Date

2025

Abstract

Background: Glioma remains an intractable and highly aggressive brain tumor, mainly due to the daunting obstacle presented by the blood-brain barrier (BBB). To overcome this challenge and enhance therapeutic efficacy, a dual-drug delivery system was engineered. This system co-encapsulated curcumin, a nutraceutical with multitargeted anticancer potential, with atorvastatin calcium, a repurposed anticancer agent, within lipidic nanocapsules (LNCs). Methods: LNCs were prepared via the phase inversion temperature method and optimized using a Box–Behnken design. The optimized LNCs were subsequently functionalized with folic acid (FA) to enable active targeting. FA-LNCs were characterized using, XPS, TEM, in vitro release, and MTT cytotoxicity assays. Atorvastatin and curcumin were radiolabeled separately with iodine-131 to evaluate the in vivo pharmacokinetics in glioma-bearing mouse model. Results: The optimized LNCs displayed a mean particle size of 97.98±2.27 nm, a polydispersity index of 0.32±0.07, and a zeta potential of −15.85±1.35 mV. XPS analysis verified FA conjugation. Both LNCs and FA-LNCs enhanced in vitro cytotoxicity compared to free drugs; however, the most pronounced effect of FA functionalization was observed in vivo. The pharmacokinetic studies showed a significant decrease in hepatic clearance and a significant two- to three-fold increase in mean residence time and blood AUC for LNCs compared to free drugs. Most significantly, FA-LNCs achieved markedly greater glioma accumulation than non-functionalized LNCs, with AUC values 2.0-fold higher for atorvastatin and 2.6-fold higher for curcumin. When compared to the free drug solutions, this efficiency was even more pronounced, with atorvastatin and curcumin showing enhancements of 8.2 and 12.4 times, respectively. Conclusions: FA-LNCs markedly improved glioma targeting efficiency and reduced systemic clearance which underscores the therapeutic potential of integrating nutraceuticals with repurposed agents to achieve effective glioma therapy.

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