Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption.
BACKGROUND
Lipid-based liquid crystalline nanoparticles (LCNPs) have attracted growing interest as novel drug-delivery systems for improving the bioavailability of both hydrophilic and hydrophobic drugs. However, their cellular interaction and in vivo behavior have not been fully developed and characterized.


METHODS
In this study, self-assembled LCNPs prepared from soy phosphatidylcholine and glycerol dioleate were developed as a platform for oral delivery of paclitaxel. The particle size of empty LCNPs and paclitaxel-loaded LCNPs was around 80 nm. The phase behavior of the liquid crystalline matrix was characterized using crossed polarized light microscopy and small-angle X-ray scattering, and showed both reversed cubic and hexagonal phase in the liquid crystalline matrix. Transmission electron microscopy and cryofield emission scanning electron microscopy analysis revealed an inner winding water channel in LCNPs and a " ball-like"/"hexagonal" morphology.


RESULTS
Cellular uptake of LCNPs in Caco-2 cells was found to be concentration-dependent and time-dependent, with involvement of both clathrin and caveolae/lipid raft-mediated endocytosis. Under confocal laser scanning microscopy, soy phosphatidylcholine was observed to segregate from the internalized LCNPs and to fuse with the cell membrane. An in vivo pharmacokinetic study showed that the oral bioavailability of paclitaxel-loaded LCNPs (13.16%) was 2.1 times that of Taxol(®) (the commercial formulation of paclitaxel, 6.39%).


CONCLUSIONS
The findings of this study suggest that this LCNP delivery system may be a promising candidate for improving the oral bioavailability of poorly water-soluble agents.
Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai.
Ni
N
Zeng
Xiaoling
X
Gao
Quanyin
Q
Hu
Qingxiang
Q
Song
Huimin
H
Xia
Zhongyang
Z
Liu
Guangzhi
G
Gu
Mengyin
M
Jiang
Zhiqing
Z
Pang
Hongzhuan
H
Chen
Jun
J
Chen
Liang
L
Fang
D000818:Animals; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004075:Diglycerides / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D010078:Oxazines / Q000737:chemistry; D017239:Paclitaxel / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D004075:Diglycerides; D004337:Drug Carriers; D010078:Oxazines; D010713:Phosphatidylcholines; C044808:nile red; D017239:Paclitaxel; C013965:diolein