pH-Sensitive Liposomal Delivery Of 5-Fluorouracil: A Targeted Approach For Breast Cancer Therapy

Breast cancer (BC) remains a leading cause of mortality worldwide, necessitating advancements in targeted therapeutic strategies.This study explores the development and in vitro evaluation of pH-sensitive liposomes for the delivery of 5fluorouracil (5-FU), a widely used chemotherapeutic agent.The liposomal formulation was designed to exploit the acidic tumor microenvironment, enhancing targeted drug release while minimizing systemic toxicity.Utilizing the thin-film hydration method, liposomes were prepared with dioleoylphosphatidylethanolamine (DOPE), cholesteryl hemisuccinate (CHEMS), and phosphatidylcholine (PC).Optimization through a Box-Behnken design identified ideal component ratios for optimal particle size, entrapment efficiency, and pH sensitivity.The formulation exhibited nanoscale particle size (~132.87nm), a polydispersity index (PDI) of 0.25, and a zeta potential of -29 mV, indicating uniformity and stability.Scanning electron microscopy (SEM) confirmed the spherical morphology, while Fourier-transform infrared spectroscopy (FTIR) validated the successful incorporation of 5-FU.Drug release studies demonstrated significant pH sensitivity, with enhanced release at pH 5.5 (70.96% at 72 hours) compared to pH 7.4.Cytotoxicity studies on MCF-7 BC cells demonstrated enhanced efficacy compared to free 5-FU.The cellular uptake demonstrate that the pH-sensitive formulation showed a considerably greater ability to be internalized by cells.This research highlights the promise of pH-sensitive liposomes in overcoming the limitations of conventional chemotherapy, offering a controlled, tumor-specific release of anticancer agents that enhances efficacy while reducing systemic side effects.