Studies On Norcantharidin Proliposome

Norcantharidin(NCTD),a derivative of cantharidin,is one of the mosteffective anticancer drugs against hepatogenic cancer,hepatocirrhosis,hepatitiscarrier , esophageal carcinoma , gastric carcinoma , breast cancer , lungcancer.One of the advantages of NCTD is that it can promote the growth ofleukocyte,which is different from other anticancer drugs.However,thesuccessful treatment with NCTD of conventional formulation remains difficultbecause of several pharmacokinetic and formulation factors that affect itsdisposition and toxicity,especially kidneys.The high concentration of NCTDwas attributed to the presence of the renal damage.Despite its side effects,NCTD is still largely used in advanced life-threatening tumors because of itshigh efficacy and low cost.Isoelectric point of NCTD was at a range from 7.2 to 7.5 determined byisoelectric focusing electrophoresis method(IEF).Chemical stability of NCTDwater solution was measured by HPLC method,which indicated that thesolution should be stored at low temperature and against light.Results aboveprovided basis for designing formulation,establishing separation and analysismethod,and studying stability of NCTD proliposomes.NCTD proliposomes were prepared by new-method . Membranecomposition,media pH value and preparation process were studied.On the baseof single factor test,uniform design was used to obtain the optimum componentof proliposomes and preparation process.This method could resolve theproblems of chemical stability of biochemical drug and physical stability ofliposomes.Studies on stability indicated that NCTD proliposomes should bestored at low temperature and against light,which ensured unchanged of theirredispersity,content of drug,encapsulation efficiency,acid value and peroxidevalue.Average particle size was 0.58 micrometer,ranging from 0.29 micrometerto 0.81 micrometer.Cryoscopic value was 0.64℃ determined by cryoscopicmethod,which was a little higher than that of isotonic solution.Zeta potentialwas -44.23 millivolt.Viscosity was 1.826 mPa·s.All of which were coincidedwith physical desire.In addition,the tests of NCTD liposomes includingirritation,hemolysis,pyrogen and hypersensibility,proved that the preparationreached the atandard of intravenous injection entirely.