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Oleanolic acid liposomes with polyethylene glycol modification: promising antitumor drug delivery

Authors Gao D, Tang S, Tong Q

Received 12 March 2012

Accepted for publication 10 April 2012

Published 6 July 2012 Volume 2012:7 Pages 3517—3526

DOI https://doi.org/10.2147/IJN.S31725

Review by Single-blind

Peer reviewer comments 4

Video abstract presented by Dawei Gao

Views: 773

Dawei Gao, Shengnan Tang, Qi Tong

Applied Chemical Key Laboratory of Hebei Province, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, China

Background: Oleanolic acid is a pentacyclic triterpene present in many fruits and vegetables, and has received much attention on account of its biological properties. However, its poor solubility and low bioavailability limit its use. The objective of this study was to encapsulate oleanolic acid into nanoliposomes using the modified ethanol injection method.
Methods: The liposomes contain a hydrophobic oleanolic acid core, an amphiphilic soybean lecithin monolayer, and a protective hydrophilic polyethylene glycol (PEG) coating. During the preparation process, the formulations described were investigated by designing 34 orthogonal experiments as well as considering the effects of different physical characteristics. The four factors were the ratios of drug to soybean phosphatidylcholine (w/w), cholesterol (w/w), PEG-2000 (w/w), and temperature of phosphate-buffered saline at three different levels. We identified the optimized formulation which showed the most satisfactory lipid stability and particle formation. The morphology of the liposomes obtained was determined by transmission electron microscopy and atomic force microscopy. The existence of PEG in the liposome component was validated by Fourier transform infrared spectrum analysis.
Results: The PEGylated liposomes dispersed individually and had diameters of around 110–200 nm. Encapsulation efficiency was more than 85%, as calculated by high-performance liquid chromatography and Sephadex® gel filtration. Furthermore, when compared with native oleanolic acid, the liposomal formulations showed better stability in vitro. Finally, the cytotoxicity of the oleanolic acid liposomes was evaluated using a microtiter tetrazolium assay.
Conclusion: These results suggest that PEGylated liposomes would serve as a potent delivery vehicle for oleanolic acid in future cancer therapy.

Keywords: oleanolic acid, liposomes, ethanol injection, polyethylene glycol

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