Optimization andin vitroanticancer evaluation of propolis-loaded niosomes: a nanotechnological strategy for enhanced...

Cancer remains a global health challenge, with conventional treatments limited by toxicity and drug resistance. Propolis, a natural resin with promising anticancer properties but restricted in clinical applications due to low bioavailability and poor solubility. Nanotechnology, offers a potential approach to enhance propolis' therapeutic efficacy through more efficient delivery and improved pharmacokinetics. Propolis-loaded niosomes (PLNs) were prepared using the ethanol injection method, optimized using response surface methodology (RSM) for surfactant type (Tween 80), cholesterol-to-surfactant ratio, and propolis content. Physicochemical properties, including particle size, polydispersity index (PDI), and zeta potential were characterized. Stability was assessed under various storage conditions, and total polyphenol content (TPC) and entrapment efficiency (EE%) were determined. Anticancer activity wasin vitroassessed against MCF7 breast cancer and L929 fibroblast cell lines. The optimized PLN formulation (at a mass ratio 4:1:8 of propolis: cholesterol: Tween 80, respectively) achieved a particle size of 193.5 nm, PDI of 0.123, and zeta potential of -19.6 mV, with a TPC of 21.83 mg GAE g^-1and EE% of 57.82%. Stability studies confirmed optimized formulation's robustness at 4 °C, with minimal changes over 42 d, though higher temperatures induced aggregation. PLNs exhibited superior cytotoxicity against MCF7 cells inhibitory concentration (IC₅₀equivalent to 106.85 µg ml^-1) compared to L929 cells (IC₅₀equivalent to 127.14 µg ml^-1). The formulation's uniformity and moderate stability support its potential for targeted drug delivery. PLNs effectively enhance propolis' anticancer efficacy and bioavailability, offering a promising delivery system for cancer therapy. Future studies should focus on improving zeta potential,in vivovalidation, and encapsulation efficiency to advance clinical translation.