Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption

Abstract

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%).

Conclusion

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.

Keywords:

• soy phosphatidylcholine
• glycerol dioleate
• liquid crystalline nanoparticles
• paclitaxel
• cellular interaction

Acknowledgment

This work was supported by the National Natural Science Foundation of China (81072592, 30801439), the National Key Basic Research Program (2010CB529800), the Innovation Program of Shanghai Municipal Education Commission (12ZZ107), and the Shanghai Science and Technology Committee (10QA1404100, 11430702200). The authors would also like to thank Tessa Nguyen for her help in editing the manuscript.

Disclosure

The authors report no conflicts of interest in this work.