Jing Zhang, Yingchong Chen, Xiang Li, Xinli Liang, Xiaojian Luo

This study was designed to improve the in vivo pharmacokinetics of long-circulating vincristine sulfate (VS)-loaded liposomes; three different long-circulating materials, chitosan, poly(ethylene glycol)-1,2-distearoyl sn-glycero-3-phosphatidylethanolamine (PEG-DSPE), and poly(ethylene glycol)-poly-lactide-co-glycolide (PEG-PLGA), were evaluated at the same coating molar ratio with the commercial product Marqibo(®) (vincristine sulfate liposome injection [VSLI]). VS-loaded liposomes were prepared by a pH gradient method and were then coated with chitosan, PEG-DSPE, or PEG-PLGA. Physicochemical properties, including the morphology, particle size, zeta potential, encapsulation efficiency (EE%), pH, drug loading, and in vitro release, were determined. Preservation stability and pharmacokinetic studies were performed to compare the membrane-coated liposomes with either commercially available liposomes or the VS solution. The sphere-like morphology of the vesicles was confirmed by transmission electron microscope. Increased particle size, especially for the chitosan formulation, was observed after the coating process. However, the EE% was ~99.0% with drug loading at 2.0 mg/mL, which did not change after the coating process. The coating of long-circulation materials, except for chitosan, resulted in negatively charged and stable vesicles at physiological pH. The near-zero zeta potential exhibited by the PEG-DSPE formulation leads to a longer circulation lifetime and improved absorption for VS, when compared with the PEG-PLGA formulation. Compared with the commercial product, PEG was responsible for a higher plasma VS concentration and a longer half-life. PEG-DSPE coating may be related to better absorption, based on the stability and a pharmacokinetic improvement in the blood circulation time.