Studies On Altretamine Liposomes For Oral Use

The HPLC analytical method for Hexamethylmelamine(HMM)in vitro was developed.The method of detecting the content of HMM and the encapsulation efficiency of HMM liposome was established,which also used in study of HMM physicochemical property and stability.The entrapment efficiency of HM liposome was determined by minicolum_n centrifuge-HPLC method.The HMM liposome was prepared by ethanol injection method.The single factor investigation and the orthogonal design were adopted to obtain the optimized prescription,the entrapment efficiency of HMM liposome was above 85%.On the base of above,the prepared technology of liposome coated chitosan was investigated and HMM liposome coated by chitosan was prepared.The HMM/DOC liposome was prepared by reverse-phase evaporation method.The single factor was investigated by taking sodium deoxycholate(DOC)as the model of bile salts and entrapment efficiency as the evaluation index.Liposomal membrane integrity was judged by bite salt-induced release of DOC-liposomes encapsulated calcein(Cal/DOC-liposomes).The optimized prescription of HMM/DOC liposome was stable in bile salts solution.The physicochemical properties of HMM liposome,HMM liposome coated by chitosan and HMM/DOC liposome were studied.The there liposomes were all spheroidal and uniform.The releasing rate of HMM/DOC liposome was slower than HMM liposome in bile salts solution;the releasing rate of HMM liposome coated by chitosan was slower than HMM liposome in chlorhydric acid;there's no difference in releasing rate of three liposomes in phosphate solution of pH 7.4.The results of stability tests indicated that three liposomes should be stored in low temperature.The detection method of HMM in plasma of rats was established.The pharmacokinetic processes in rats for the three liposomes and HMM solution,which were administrated orally, were accorded with two compartmental models.Compared with HMM liposome,the HMM liposome coated by chitosan and HMM/DOC liposome both had longer half-life and higher relative bioavailability.