title: Oleanolic acid liposomes with polyethylene glycol modification: promising antitumor drug delivery.
abstract: 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.
  
  
  CONCLUSIONS
  These results suggest that PEGylated liposomes would serve as a potent delivery vehicle for oleanolic acid in future cancer therapy.
authors: Applied Chemical Key Laboratory of Hebei Province, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, China. dwgao@ysu.edu.cn
authors: Dawei
authors: D
authors: Gao
authors: Shengnan
authors: S
authors: Tang
authors: Qi
authors: Q
authors: Tong
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D004355:Drug Stability; D000431:Ethanol; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D009828:Oleanolic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D010713:Phosphatidylcholines; D000431:Ethanol; D011092:Polyethylene Glycols; D009828:Oleanolic Acid; D002784:Cholesterol