DEVELOPMENT, OPTIMIZATION AND CHARACTERIZATION OF A COW GHEE-BASED DOXORUBICIN NANOEMULSION FOR ENHANCED DRUG DELIVERY IN LUNG CANCER

Abstract

Background Lung cancer continues to be a major contributor to cancer-associated deaths across the globe. Although doxorubicin is a potent anticancer agent, its therapeutic use is limited by several pharmacokinetic and safety-related drawbacks, including systemic adverse effects, low bioavailability following oral administration, rapid clearance from the body, and inadequate selectivity toward target tissues. Nanoemulsion-based drug delivery systems have emerged as promising carriers to improve the therapeutic performance of poorly soluble anticancer agents. Natural lipid carriers such as cow ghee have gained increasing attention because of their excellent biocompatibility, antioxidant properties, and ability to enhance drug solubilization and stability. Objective The current investigation was undertaken to formulate, optimize, and characterize a cow ghee-based doxorubicin nanoemulsion to improve physicochemical characteristics, drug entrapment, controlled drug release, and formulation stability for potential application in lung cancer therapy. Methods Doxorubicin was incorporated into a nanoemulsion system in which cow ghee and mustard oil constituted the lipid phase, while Tween 60 and polyethylene glycol 400 serving as the surfactant and co-surfactant, respectively. The formulation was produced by an ultrasonication-assisted method. A three-factor, three-level Box–Behnken experimental design was employed to optimize the critical formulation variables. The optimized nanoemulsion was subsequently evaluated for particle size, polydispersity index (PDI), zeta potential, and drug entrapment efficiency. Additional characterization was carried out using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), together with in vitro drug-release evaluation and accelerated stability studies. Results The selected nanoemulsion exhibited suitable physicochemical properties, with a mean particle size of 132.07 ± 2.31 nm, a polydispersity index (PDI) of 0.282 ± 0.005, and a zeta potential of −32.6 ± 0.47 mV. The formulation also achieved a drug entrapment efficiency of 93.48 ± 0.69%, indicating substantial incorporation of doxorubicin into the nanoemulsion system. The observed zeta potential was consistent with good colloidal stability. The FTIR and DSC findings revealed no notable incompatibility between the drug and the selected formulation components. In vitro release testing demonstrated prolonged drug release from the optimized nanoemulsion, with 78.94% of doxorubicin released over 24 h. In comparison, the conventional doxorubicin suspension showed substantially faster release, reaching 98.56% within 8 h. Furthermore, only minor changes in particle size, PDI, and entrapment efficiency were observed during the 90-day accelerated stability study, supporting the satisfactory physical stability of the optimized formulation. Conclusion The developed cow ghee-based doxorubicin nanoemulsion demonstrated desirable favorable physicochemical characteristics, efficient incorporation of the drug, sustained in vitro release behavior, and acceptable physical stability under short-term accelerated storage conditions. These findings support further investigation of cow ghee as a natural lipid carrier for doxorubicin. Potential improvements in anticancer efficacy or systemic safety require confirmation by cell-based and in vivo studies.