Biometallic Synthesis of Gel-Loaded Copper Nanoparticles Using Manilkara zapota L. Extract: Phytochemical Profiling and Breast Cancer Evaluation

Abstract

Background: Manilkara zapota L. is rich in bioactive phytochemicals with reported anticancer properties. The incorporation of copper nanoparticles (CuNPs) into Carbopol gels may increase their therapeutic potential and facilitate controlled, pH-sensitive delivery.

Methods: Petroleum ether extracts of M. zapota aerial part were prepared and phytochemically characterized via qualitative analysis, HPTLC, and GC-MS. CuNPs were synthesized via green reduction and incorporated into a Carbopol gel. The formulation was evaluated for its particle size, zeta potential, morphology, entrapment efficiency, stability, pH-sensitive release, and cytotoxic potential against MCF-7 breast cancer cells and MCF-10A normal cells.

Results: The extract contained phenols, flavonoids, anthocyanins, steroids, and cardiac glycosides. HPTLC bands were observed at Rf values of 0.70, 0.76, and 0.88. The major GC-MS compounds included β-sitosterol acetate, 3β-acetoxystigmasta-4,6,22-pentatriacontene. The CuNPs were 286.2 nm in size with a zeta potential of −6.6 mV and 86.83% entrapment efficiency. The gel demonstrated optimal viscosity, pH 6.8–7.4, sustained release (pH 6.5: 91.53%, pH 7.4: 72.56%), cytotoxicity against MCF-7 cells (IC₅₀ = 36.04 µg/mL), minimal toxicity to MCF-10A cells, and stability over 3 months. The release kinetics followed the Korsmeyer–Peppas model (n = 0.58).

Conclusion: The CuNP-loaded gel from M. zapota extract exhibited sustained, pH-sensitive, and selective anticancer activity with excellent stability, supporting its potential translational application.