title: The pharmacokinetics of chelerythrine solution and chelerythrine liposomes after oral administration to rats.
abstract: Chelerythrine is a quaternary benzo[c]phenanthridine alkaloid which has many potent pharmacological effects and can dissolve well in water; dihydrochelerythrine has recently been identified as a chelerythrine metabolite in rat. Most methods of preparation of liposomes suffer from the drawback of poor incorporation of water-soluble drugs. The emulsion/solvent evaporation method is a relatively simple and efficient way to prepare liposomes loaded with hydrophilic drugs. The aim of this study was therefore to find a suitable formulation to enhance the incorporation of chelerythrine into liposomes by the emulsion/solvent evaporation method and so improve the therapeutic efficacy of chelerythrine. Results showed that the chelerythrine-liposome has been successfully prepared by the emulsion/solvent evaporation method: the entrapment efficiency of chelerythrine was higher at 78.6 %, and the drug loadings reached 7.8 %. The relative bioavailability of chelerythrine and its dihydro derivative in liposomes was significantly increased compared with that of the chelerythrine solution. The area under the plasma concentration-time curve values of chelerythrine and dihydrochelerythrine after oral administration of chelerythrine-liposomes were 4.83-fold and 2.02 higher than those obtained with the chelerythrine solution. The half time and peak concentrations of chelerythrine and dihydrochelerythrine were also higher for chelerythrine-liposomes than that for chelerythrine. In contrast, the total body clearance and apparent volume of distribution were lower for chelerythrine-liposomes in comparison to the respective parameters for the chelerythrine solution. It can thus be concluded that incorporation into liposomes prolonged chelerythrine retention within the systemic circulation.
authors.affiliation: School of Medicine, Xi'an Jiaotong University, Xi'an, PR China. liwf@mail.xjtu.edu.cn
authors.forename: Weifeng
authors.initials: W
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Niu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Ting
authors.initials: T
authors.lastname: Fan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D053119:Benzophenanthridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008081:Liposomes; D008854:Microscopy, Electron; D010316:Particle Size; D051381:Rats; D012996:Solutions
chemical_list: D053119:Benzophenanthridines; D008081:Liposomes; D012996:Solutions; C016299:chelerythrine