Preparation, characterization, pharmacokinetics and anticancer effects of PEGylated beta-elemene liposomes

Objective: This study aimed to develop a new polyethylene glycol (PEG)ylated beta-elemene liposome (PEG-Lipo-beta-E) and evaluate its characterization, pharmacokinetics, antitumor effects and safety in vitro and in vivo. Methods: The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization. Characterization of the liposomes was conducted, and drug content, entrapment efficiency (EE), in vitro release and stability were studied by ultra-fast liquid chromatography (MC) and a liquid surface method. Blood was drawn from rats to establish the pharmacokinetic parameters. The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model. Histological analyses were performed to evaluate safety. Results: The PEG-Lipo-beta-E showed good stability and was characterized as 83.31 +/- 0.181 nm in size, 0.2791 0.004 in polydispersity index (PM), -21.4 +/- 1.06 mV in zeta potential, 6.65 ! 0.02 in pH, 5.024 +/- 0.107 mg/mL in beta-elemene (beta-E) content, and 95.53 +/- 1.712% in average EE. The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) indicated the formation of PEG-Lipo-beta-E. Compared to elemene injection, PEG-Lipo-beta-E demonstrated a 1.75-fold decrease in clearance, a 1.62-fold increase in half-life, and a 1.76-fold increase in area under the concentration-time curves (AUCs) from 0 hour to 1.5 hours (P < 0.05). PEG-Lipo-beta-E also showed an enhanced anticancer effect in vivo. Histological analyses showed that there was no evidence of toxicity to the heart, kidney, liver, lung or spleen. Conclusions:The present study demonstrates PEG-Lipo-beta-E as a new formulation with ease of preparation, high EE, good stability, improved bioavailability and antitumor effects.