PH-sensitive adriamycin hydrochloride and oxaliplatin dual-loaded microspheres synergistically enhance local injections effect of hepatocellular carcinoma

Abstract

Chemotherapy is the primary palliative treatment for advanced hepatocellular carcinoma (HCC). However, the systemic delivery is associated with the drawbacks including a high risk of adverse effects and a low efficacy. Therefore, local injection therapy may be beneficial. Nevertheless, the existing local drug-carrying microspheres(DOBM)have the characteristics of low loading and abrupt release, can not simultaneously load two drugs, and may cause unnecessary toxicity. In this study, we created the dual-loaded bovine serum albumin (BSA) microspheres (also known as DOBM), which were hollow and contained both oxaliplatin (OXA) and Adriamycin hydrochloride (DOX). In addition, this pH-sensitive drug delivery method exhibited a high drug loading capacity and was promising in breaking through biological barriers, making it a viable option for the treatment of HCC through local implantation. Based on physiochemical evaluation of BSA microspheres, they had a porous structure which was close to the surface. Adriamycin and oxaliplatin were successfully added to the surface of BSA microspheres. According to in vitro experimental results, the growth of human HCC (HCC-LM3 and PLC/PRF/5) cell lines was significantly inhibited by DOBM. Furthermore, in the subcutaneous PLC/PRF/5 HCC model, DOBM played an essential role in tumor development and change in the tumor microenvironment.