Preparation, characterization, pharmacokinetics and anticancer effects of PEGylated β-elemene liposomes
Bingtao Zhai, Qibiao Wu, Wengang Wang, Mingming Zhang, Xuemeng Han, Qiujie Li, Peng Chen, Xiaying Chen, Xingxing Huang, Guohua Li, Qin Zhang, Ruonan Zhang, Xiang Yu, Shuiping Liu, Ting Duan, Jian-Shu Lou, Tian Xie, Xinbing Sui
Abstract
<h3>Objective:</h3> This study aimed to develop a new polyethylene glycol (PEG)ylated β-elemene liposome (PEG-Lipo-β-E) and evaluate its characterization, pharmacokinetics, antitumor effects and safety <i>in vitro</i> and <i>in vivo</i>. <h3>Methods:</h3> 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), <i>in vitro</i> release and stability were studied by ultra-fast liquid chromatography (UFLC) 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. <h3>Results:</h3> The PEG-Lipo-β-E showed good stability and was characterized as 83.31 ± 0.181 nm in size, 0.279 ± 0.004 in polydispersity index (PDI), −21.4 ± 1.06 mV in zeta potential, 6.65 ± 0.02 in pH, 5.024 ± 0.107 mg/mL in β-elemene (β-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-β-E. Compared to elemene injection, PEG-Lipo-β-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 (<i>P</i> < 0.05). PEG-Lipo-β-E also showed an enhanced anticancer effect <i>in vivo</i>. Histological analyses showed that there was no evidence of toxicity to the heart, kidney, liver, lung or spleen. <h3>Conclusions:</h3> The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation, high EE, good stability, improved bioavailability and antitumor effects.