PREPARATION OF CINOBUFAGIN-LOADED BOVINE SERUM ALBUMIN NANOPARTICLES FOR HEPATOCARCINOMA THERAPY
Abstract
Cinobufagin-loaded bovine serum albumin nanoparticles were prepared for treating hepatocellular carcinoma. In this report, cinobufagin-bovine serum albumin-nanoparticles (Cino-BSA-NP) were prepared by an aqueous desolvation process. The physicochemical properties, toxicity, and cancer-related applications of Cino-BSA-NP were investigated. Cino-BSA-NP had a uniform spherical morphology with a particle size in the range of 50–240 nm and an average size of 86.3 nm. The zeta potential of the nanoparticles was -49 mV. The overall embedding ratio was 79.5% and the drug loading was 24.1%. Cino-BSA-NP gave cinobufagin release of up to 53.5% within 3 h, followed by slower controlled release. Cino-BSA-NP inhibited growth of hepatocarcinoma cells in vitro to a similar extent as free cinobufagin, but with a much higher median lethal dose (LD50). Hepatic histomorphological changes indicated that hepatic damage was much less severe with Cino-BSA-NP than with free cinobufagin (2.19 mg/kg). The survival time of nude mice with orthotopic transplantation tumors treated with Cino-BSA-NP was prolonged significantly. The results confirm that Cino-BSA-NP renders cinobufagin completely dispersible in aqueous media, meeting the key requirements for intravenous injection, and show controlled release, thus significantly improving cinobufagin's antitumor activity while reducing its side effects.
