Background and Purpose Paclitaxel’s clinical use is limited by poor aqueous solubility and Cremophor EL–related toxicity in commercial formulations. This study aimed to develop a self‐nanoemulsifying drug delivery system (SNEDDS) to improve paclitaxel solubility, bioavailability, and anticancer efficacy. Experimental Approach Paclitaxel‐loaded SNEDDSs were prepared using oleic acid, Tween 80, and polyethylene glycol (PEG) 400 in different ratios and characterized for particle size, polydispersity index (PDI), zeta potential, and solubility. The optimized formulation (F1) was assessed for cytotoxicity, cell cycle distribution, apoptosis, mitochondrial membrane potential (MMP), and nuclear morphology in MCF‐7 breast cancer cells. Key Results Formulation F1 (10% oleic acid, 10% PEG 400, and 80% Tween 80) exhibited the highest solubility, smallest particle size, and lowest PDI, with near‐neutral zeta potential ensuring stability. F1 demonstrated superior cytotoxic activity, inducing G 2 /M arrest (41.8%) and total apoptosis of 70.6%, mainly in the early phase (64.4%), compared to pure paclitaxel and Paxol. MMP and 4 ′ , 6‐diamidino‐2‐phenylindole (DAPI) assays confirmed mitochondrial‐mediated apoptosis and nuclear fragmentation, consistent with paclitaxel’s mechanism of microtubule stabilization and mitotic catastrophe. Conclusion and Implications Encapsulation of paclitaxel into SNEDDS significantly enhanced solubility, cellular uptake, and proapoptotic activity. The optimized F1 formulation provides a promising nanocarrier platform for improving paclitaxel’s therapeutic performance and may serve as a safer, more effective alternative to Cremophor EL–based products for breast cancer treatment.
Almehmady et al. (2026) studied this question.