The Studies On Irinotecan Hydrochloride Liposomal Lyophilized Microparticles

The study is to evaluate the feasibility of preparing liposomal lyophilizedmicroparticles by SFD. Ammonium sulfate gradient and SFD were utilized tomanufacture liposomal lyophilized microparticles containing CPT-11as activeingredient, and the process parameters of SFD were optimized by Box-Behnkendesign. Besides the physicochemical characters of the fabricated liposome andliposomal lyophilized microparticles were analysed, the stability of CPT-11liposomallyophilized microparticles has been investigated. The results showed that the finalCPT-11liposomal lyophilized microparticles had the same physichemical characterswith the primary liposome, and exhibited good stability during long term storage. Inconlusion the liposomal lyophilized microparticles can be fabricated by SFDeffectively, and possess better stability compared with the primary liposome.Finally, the in vivo pharmacokinetics behavior and gastrointestinal side effect ofCPT-11solution and CPT-11liposomal lyophilized microparticles were evaluatedthrough the cross-over design （two periods）. CPT-11in plasma of6rats at differentsampling time was determined by RP-HPLC. The phartnacokinetic paramelers werecaleulated by3P97program and compared by statistic analysis. The pharmacokineticparameters of CPT-11liposomal lyophilized microparticles and CPT-11solution wereas follows: the clearance rate constant （K） were0.071min-1and0.37min^-1respectively, suggesting CPT-11liposome can reduce the clearance of CPT-11; Thearea under curve （AUC） were382±65μg·min·mL^-1and98±57μg·min·mL^-1,suggesting the CPT-11liposome can improve the bioavailability of drug. The evaluationof gastrointestinal side effect showed that the CPT-11liposomal lyophilizedmicroparticles lowered the toxicity greatly compared to the CPT-11solutionmanifesting that the liposome can evidently reduce the toxicity of encapsulated drugs.