Gastric cancer combination therapy: synthesis of a hyaluronic acid and cisplatin containing lipid prodrug coloaded with sorafenib in a nanoparticulate system to exhibit enhanced anticancer efficacy and reduced toxicity

Purpose: Gastric cancer is one of the most common human epithelial malignancies, and using nanoparticles (NPs) in the diagnosis and treatment of cancer has been extensively studied. The aim of this study was to develop hyaluronic acid (HA) containing lipid NPs coloaded with cisplatin (CDDP) and sorafenib (SRF) for the treatment of gastric cancer. Materials and methods: HA and CDDP containing lipid prodrug was synthesized using polyethylene glycol (PEG) as a linker (HA-PEG-CDDP). HA-PEG-CDDP and SRF were entrapped into the lipid NPs by nanoprecipitation method (H-CS-NPs). The physicochemical and biochemical properties such as size, zeta potential, and drug release pattern were studied. In vitro viability was also evaluated with MKN28 and SGC7901 human gastric cancer cells. In vivo testing including biodistribution and accumulation in tumor tissue was applied in gastric tumor-bearing mice to confirm the inhibition of gastric cancer. Results: H-CS-NP has a particle size of 173.2 +/- 5.9 nm, with a zeta potential of -21.5 +/- 3.2 mV. At day 21 of in vivo treatment, H-CS-NPs inhibited the tumor volume from 1,532.5 +/- 41.3 mm(3) to 259.6 +/- 16.3 mm(3) with no obvious body weight loss. In contrast, mice treated with free drugs had body weight loss from 20 to 15 g at the end of study. Conclusion: The results indicate that H-CS-NPs enhanced the antitumor effect of drugs and reduced the systemic toxicity effects. It could be used as a promising nanomedicine for gastric cancer combination therapy.