The influence of different long-circulating materials on the pharmacokinetics of liposomal vincristine sulfate.
OBJECTIVE
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]).


METHODS
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.


RESULTS
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.


CONCLUSIONS
PEG-DSPE coating may be related to better absorption, based on the stability and a pharmacokinetic improvement in the blood circulation time.
Key Laboratory of Modern Preparation of TCM, Ministry of Education.
Jing
J
Zhang
Key Laboratory of Modern Preparation of TCM, Ministry of Education.
Yingchong
Y
Chen
Key Laboratory of Modern Preparation of TCM, Ministry of Education; State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China.
Xiang
X
Li
Key Laboratory of Modern Preparation of TCM, Ministry of Education.
Xinli
X
Liang
State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China.
Xiaojian
X
Luo
D000818:Animals; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D014750:Vincristine / Q000493:pharmacokinetics*
D008081:Liposomes; D010714:Phosphatidylethanolamines; D011091:Polyesters; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; C000589473:polyethylene glycol-poly(lactide-co-glycolide); C483858:phosphatidylethanolamine; D011092:Polyethylene Glycols; D014750:Vincristine; D048271:Chitosan
long-circulating materials; pharmacokinetics; stability; vincristine sulfate; zeta potential