title: Preparation and characterization of paclitaxel-loaded DSPE-PEG-liquid crystalline nanoparticles (LCNPs) for improved bioavailability.
abstract: Lipid-based liquid crystalline nanoparticles (LCNPs) have attracted growing interest as a new drug nanocarrier system for improving bioavailability for both hydrophilic and hydrophobic drugs. In this study, self-assembled LCNPs based on soy phosphatidyl choline and glycerol dioleate, which was known possessing low toxicity and negligible hemolysis, were prepared using poly(ethylene glycol)-grafted 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE-PEG) as the dispersing agent. Paclitaxel (PTX) was used as a model hydrophobic drug. The particle size of the optimized DSPE-PEG-LCNPs and PTX-loaded DSPE-PEG-LCNPs were around 70nm. Crossed polarized light microscopy was used to characterize the phase behavior of liquid crystalline (LC) matrices, which showed a fan-like birefringent texture in dark background indicating the coexistence of reversed cubic and hexagonal phase in the optimized LC matrix. Transmission electron microscopy and cryo-field emission scanning electron microscopy revealed its internal water channel and "twig-like" surface morphology. PTX-loaded DSPE-PEG-LCNPs exhibited a biphasic drug sustained release pattern with a relatively fast release at the initial stage and a sustained release afterwards. PTX-loaded DSPE-PEG-LCNPs presented higher AUC (410.942±72.522μg/Lh) when compared with commercial product Taxol (212.670±41.396μg/Lh). These results indicated that DSPE-PEG-LCNPs might serve as a potential sustained release system for poorly water-soluble agents.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Zhangheng Road, Shanghai, PR China.
authors.forename: Ni
authors.initials: N
authors.lastname: Zeng
authors.forename: Quanyin
authors.initials: Q
authors.lastname: Hu
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Liu
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.forename: Rongkuan
authors.initials: R
authors.lastname: Hu
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Song
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Gu
authors.forename: Huimin
authors.initials: H
authors.lastname: Xia
authors.forename: Lei
authors.initials: L
authors.lastname: Yao
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000737:chemistry* / Q000493:pharmacokinetics; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D017239:Paclitaxel