Study On The Long-circulated HCPT Liposome

HCPT (10-hydrocamptothecin) is extracted from Camptotheca acuminata Decaisne. HCPT has been tested widely effective against cancers as liver cancer, stomach cancer and leucocythemia etc. Now HCPT injection is used as the first-line optimal anti-cancer drug in clinic.In the present study, HCPT is taken as the model drug and loaded by PC with F-68 as the modifier to prepare HCPT long-circulated liposome (HCPT-lipo). The main purpose of this project is to prolong the time of HCPT residual in blood circumstance and get stronger effects. All aspects of HCPT-lipo were investigated in detail and systematically, including the physical and chemical characteristic, properties of pharmacy, distribution and pharmacokinetics in vivo etc.In order to screen the most optimal preparing technology, several preparing method of liposome have been tested including dry-membrane method, inject method, multi-emulsification method and emulsification-evaporation method. The dry-membrane method is employed for preparing the liposome without membrane modifier. The emulsification-evaporation method is employed for preparing the HCPT-lipo. The entrapment ratio (ER) and the stability are taken as criterions to evaluate the effects of ten factors such as the ratio of HCPT and PC, the ratio of PC and CHO and the emulsification conditions etc.on the properties of HCPT-lipo. Then the optimal formulation and process is determined and repeated. The optimal formulation was simple, so it could improve the stability of HCPT-lipo, the ER was high enough which implied HCPT-lipo could be in full use in this formulation.The formulation of HCPT-lipo lyophilyzation injection was optimized based on its particle size, ER and dispersing properties. As a result, the problem that the colloidal solution was not stable and difficult to disperse in water was resolved. The stability of HCPT-lipo was not affected by the formulation of HCPT-lipo lyophilyzation injection with nearly unchanged particle size, entrapment ratio etc. Through measuring the trans-phase temperature of HCPT-lipo, the membrane of liposome is tested stable.The stability test and safety test have been developed. The results indicate that the HCPT-lipo can keep an intergrated shade after 48hr in plasma and the particle size and theentrapment ratio are nearly unchanged after 3 months accelerated test. It also get a pass result in the safety test.An RP-HPLC method was established to determine HCPT in plasma of rats after i.v. administration of HCPT-lipo lyophilizationl(F-68 as the modifier), HCPT-lipo lyophilization2(F-68 and Chitosan as the modifier), HCPT liposome (without modifier) and HCPT injection. The curve of C-T is described and the PK parameters are calculated as well as T test. The results show that in comparison with the other three terms, the HCPT-lipo lyophilizationl(F-68 as the modifier) can prolong the time of HCPT residual in blood circumstance and shows statistics differences in AUC and Cmax.The tissue distribution of HCPT-lipo lyophilizationl(F-68 as the modifier) is studied in comparison with HCPT injection. The HCPT-lipo lyophilizationl(F-68 as the modifier) also prolong the time of HCPT residual in blood circumstance as got in rats and shows statistics differences with HCPT injection in tissue distribution. The HCPT-lipo lyophilizationl(F-68 as the modifier) is mainly metabolized by liver.To sum up, the results of the study revealed that HCPT-lipo, which was easy to prepare and could improve the stability of drug, is an effective drug delivery system. Due to there being no report about HCPT-lipo, the accomplishment of this project is a achievement of liposome.