DESIGN AND DEVELOPMENT OF LIGAND ASSOCIATED SORAFENIB TOSYLATE NANOPARTICLES FOR LIVER CANCER

Objective: Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and is associated with cirrhosis and non-alcoholic fatty liver disease. Sorafenib is used to treat HCC; however, it is associated with significant toxicity and low bioavailability, resulting in a narrow therapeutic window. This study aimed to develop chondroitin sulphate–functionalized PLGA nanoparticles encapsulating sorafenib tosylate for targeted delivery to hepatocellular carcinoma cells. Methods: A PLGA-PEG-CS graft copolymer was synthesized in the laboratory and used to prepare sorafenib tosylate–loaded nanoparticles. Formulation optimization was carried out using a Box–Behnken design. The optimized nanoparticles were evaluated for particle size, PDI, entrapment efficiency, in vitro drug release, and cytotoxicity using HepG2 cell lines. Results: The optimized sorafenib tosylate–loaded nanoparticles showed a particle size of 320.23 nm, a PDI of 0.26, an entrapment efficiency of 55.53%, and a cumulative drug release of 83.12% within 360 min. Drug release followed the Korsmeyer–Peppas model, indicating Fickian diffusion–controlled release with minimal polymer erosion. Additionally, the optimized formulation exhibited 58.60% cytotoxicity in the MTT assay. Conclusion: Sorafenib tosylate–loaded PLGA-PEG-CS nanoparticles were developed to enable targeted delivery to hepatocellular carcinoma cells. The formulation exhibited desirable critical quality attributes, including small particle size, low PDI, high entrapment efficiency, and sustained drug release. The optimized nanoparticles demonstrated enhanced in vitro cytotoxicity compared to free sorafenib tosylate in MTT assays, which may be attributed to improved cellular uptake and enhanced intracellular drug delivery.