Preparation And Evaluation Of Liver-targeted Capecitabine Liposomes

ObjectIn this study, bromoacetyl galactose and styearyl alcohol were used tosynthesize styearyl alcohol galactosidase, then the styearyl alcoholgalactosidase was used as modified materials to preparate liver-targetedcapecitabine liposomes, expecting this kind of liposomes could obtain thequality of liver-targeting, reduce the toxic and side effect, reduce the drugdosage and frequency and finally improve the treatment effect.MethodsThe capecitabine was studied before the prescription, analytical methodswere established and methodology certification was carried on, at the sametime the basic physical and chemical properties were inspected. Bromoacetylgalactose and styearyl alcohol were used as raw materials to synthesizestyearyl alcohol galactosidase through a series of reactions, provided guidancemolecules for the preparation of liver-targeted capecitabine liposomes.Microcolumn centrifugation–HPLC was employed to detect the encapsulationefficiency of liver-targeted capecitabine liposomes. The encapsulation efficiencywas ueded as rewiew indicators to choose the suitable methods that preparedthe liver-targeted capecitabine liposomes, at the same time the single factorinvestigation and orthogonal design were applied to optimum preparation. Themorphology and particle size and encapsulation efficiency of the liposome thatprepared by the choosed method and the optimal prescription were investigated. The suitable tissue sample treatment was selected, analyticalmethod in vivo was established and methodology certification was carried out.The mice were grouped and given the drug and taken the tissue according tothe experimental design. The capecitabine was analysed in vivo after thetreatment of tissue sample, then the liver-targeting of the liver-targetedcapecitabine liposomes was studied.ResultIn this study, the most suitable analytical method in vitro of capecitabinewas established, and the investigation of the basic physical and chemicalproperties showing is suitable for the preparation of liposome. Through themass spectrometry, we affirm synthetize the styearyl alcohol galactosidasesuccessfully. Microcolumn centrifugation–HPLC was suitable to detect theencapsulation efficiency of liver-targeted capecitabine liposomes. The resultshowed that the optimal preparation condition were as follow: phospholipidconcentration was5mg/mL, ratio of phospholipid to cholesterol was5∶1, ratioof18-Gal to lipid was1∶20, the encapsulation efficiency of liver-targetedcapecitabine liposomes that prepared by the optimal prescription was82.47%,particle size was (193±11) nm, the form was spherical or nearly spherical. Theliver targeting index of liver-targeted capecitabine liposomes was4.09,preliminary verified the liver-targeting of the liposome.ConclusionThe encapsulation efficiency of liver-targeted capecitabine liposomes thatprepared by the optimal prescription was high, the partical size was uniform, theliver-targeting was significant.