Development and Estimation of Lipid Hybrid Nanocarriers Co-Loaded Oxaliplatin and Melatonin for Breast Cancer

Breast cancer remains the most frequently diagnosed cancer worldwide and the second leading cause of cancer-related mortality among women. Drug resistance and significant adverse effects limit anticancer drugs efficacy despite their availability. Oxaliplatin (OXA), a platinum-based chemotherapeutic agent, has shown potential in metastatic breast cancer, however its toxicity limit its use. Melatonin (MEL) demonstrates anticancer activity and improves chemotherapy efficacy, but its therapeutic use is limited by poor stability and short half-life. Nanocarriers, particularly lipid-polymer-hybrid nanoparticles (LPNs), offer an innovative approach to improve drug delivery, enhance bioavailability, and limited systemic toxicity. OXA and MEL co-encapsulated LPNs were prepared. Design of Experiments (DoE)-based optimization was employed using the Box-Behnken design (BBD) to systematically evaluate critical formulation parameters. Particle size, polydispersity index, zeta potential, encapsulation efficiency, release, FTIR, DSC and stability studies were carried out. The effects of OXA-MEL-loaded-LPNs were assessed on human breast cancer cell line (MCF-7). Optimized LPNs exhibited a particle size of ∼240 nm, PDI of 0.17, zeta potential of -30 mV, and encapsulation efficiencies of 99.1% for MEL and 96.1% for OXA. In vitro release studies showed sustained release, with ∼26% OXA and ∼18% MEL released over 8hours. FTIR and DSC analysis showed all substances were loaded into particles. Stability data indicate that particle size remains within the acceptable range for up to one week. Lyophilization resulted in a slight increase in particle size and PDI. Co-loaded LPNs exhibited significant cellular cytotoxicity. The findings suggest that LPNs offer a promising platform for combination therapy, potentially improving treatment outcomes in breast cancer.