Study On The Microparticle Administration System Of Irinotecan Hydrochloride Carrier Material

Irinotecan hydrochloride（CPT-11）is a semi-synthetic derivative of camptothecin,yellow crystalline powder, slightly fragrant. It is one of the three major discoveries ofanticancer drugs in1990s and has curative effect and small side effect and is used asspecific drug for advanced colorectal cancer. For the patients failed with5-fluorouracil chemotherapy, it can be used as a second-line therapy. At the sametime, it has effect to small cell and non-small cell lung cancer, as well as cervicalcancer and ovarian cancer. CPT-11is soluble in water and methanol, slightly solublein chloroform and alcohol and almost insoluble in acetone and ethyl ether. Currently,the listed products only have traditional injection. The imported drug Campto is madeby Pfizer Pharm. There are three pharmaceutical enterprises producing CPT-11injection at home. They are Jiangsu Hengrui medicine Limited by Share Ltd. Products“Aili”，Qilu Pharmaceutical（Hainan）Co. Ltd. and Shanghai ChuangnuoPharmaceutical Company Limited. The drug caused severe diarrhea and bone marrowsuppression in large doses, which is considered to be related to dosage toxicity.Therefore, it is necessary to prepare drug delivery system using preparation method.Polymeric micelles are formed by amphiphilic block copolymer self-assemblingin water phase. It is proposed as a drug carrier for the first time by Bader in1984. Thehydrophilic part forms a hydrophobic core, meanwhile the hydrophobic portion formsshell. It can improve the distribution of the drug in vivo and cycling time, reduce sideeffect and enhance the treatment effect when drug was loaded into the micelles. Thisproject takes mPEG-PCL as carrier material to prepare CPT-11micelles.Micelles has high entrapment efficiency for lipophilic drugs, while CPT-11is ahydrophilic drug and not easy to be loaded into the hydrophobic core of micelles. Wemodify CPT-11firstly and make it into phytosome, and then entrap it into the carriermaterial to prepare micelle drug delivery.Used Chloroform as the reaction solvent, through single factor and orthogonaltest, to determine the optimal preparation technology as follows: the mass ratio ofCPT-11and phosphatide is1:5, the reaction lasts1.5h at45℃. Then add diethyl ether dissolved again to except the free drug. The binding rate is up to98.65%determinedby HPLC. Through testing the oil-water partition coefficient and characterized usingDSC, phytosome increases the lipophilic of CPT-11significantly.The method is using phytosome as active ingredient and mPEG-PCL as carriermaterials prepare micelle drug delivery. Through selecting factors such as preparingmethod, organic solvent, the ratio of organic phase and water phase, the amount ofmaterial and reaction duration, optimizing the formulation and process. Thepreparation method is as follows: the ratio of organic phase and water phase is2:10,the amount of carrier material is100mg, adding1ml CPT-11phytosome, Droppingthe mixture into stirring water, Removing the organic solvent and filtering to getmicelles loading drugs. The morphology of micelles is spherical or nearly sphericalobserved by SEM. The particle size and Zeta potential were measured by DLS. Themean diameter of mPP2k blank micelle is57.88nm, micelle loading drugs is125.6nm,mPP5k blank micelle is90.47nm and the one loading drugs is156.20nm. Zetapotential: the mean potential of mPP2k blank micelle is-15.03mV, micelle loadingdrugs is-14.2mV, mPP5k blank micelle is-12.3mV and the one loading drugs is-7.35mV. The mean entrapment efficiency of micelle is61.32%determined byHPLC.Preparing micelles drug delivery system by improving the lipophilic of CPT-11through preparing phytosome and then taking the phytosome entrapped into carriermaterials. The preparation method is simple and easy, at the meanwhile, the particlesize distribution of micelle prepared is uniform. This study laid a foundation to thetargeting delivery of CPT-11.