环孢素a壳聚糖衍生物胶束的制备及其大鼠口服生物利用度(1)

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1、学报208JournalofChinaPharmaceuticalUniversity2007,38(3):208-212环孢素A壳聚糖衍生物胶束的制备及其大鼠口服生物利用度X刘蕾,平其能,张灿,刘敏霞(中国药科大学药剂学教研室,南京210009)摘要目的:制备环孢素A(CyA)壳聚糖衍生物胶束(CyA2CDM),研究其在大鼠体内的口服生物利用度,并与其上市制剂进行比较。方法:采用水溶性壳聚糖衍生物以自乳化溶剂挥发法制备环孢素A聚合物胶束,测定其载药量、包封率和R○粒径。以市售制剂Gengraf为参比,对大鼠灌胃给药,用HPLC测定

2、全血药物浓度,考察二者的药代动力学特征和相对生物利用度。结果:壳聚糖衍生物胶束载药量为(23139±0124)%,包封率为(91199±2185)%,粒径为(26017±5101)nm。与R○Gengraf相比,壳聚糖衍生物胶束的相对生物利用度为97107%,峰浓度略大(P<0105),分布和消除过程与对照品没有显著R○性差异(P<0105)。结论:环孢素A壳聚糖衍生物胶束具有良好的载药性能,口服吸收良好,在大鼠体内显示与Gengraf相近的生物利用度。关键词环孢素A;胶束;N2辛基2O2磺酸基壳聚糖;生物利用度中图分类号R944文

3、献标识码A文章编号1000-5048(2007)03-0208-05PreparationofchitosanderivativemicellescontainingcyclosporineAanditsoralbioavailabilityinratsLIULei,PINGQi2neng,ZHANGCan,LIUMin2xiaDepartmentofPharmaceutics,ChinaPharmaceuticalUniversity,Nanjing210009,ChinaAbstractAim:Inordertodevelopa

4、newcarriersystem,cyclosporineA(CyA)loadedchitosanderivativemicelles(CyA2CDM)wereprepared,andthepharmacokineticsandoralbioavailabilitiesofCyA2CDMwerecomparedwiththoseR○ofthecommercialproductGengraf.Methods:CyA2CDMwaspreparedbyself2emulsificationsolventevaporation.R○CyA2

5、CDMandGengrafwereorallyadministratedtoratsinthedosageof10mg/kg,respectively.WholebloodCyAconcentrationwasdeterminedbyHPLC.Pharmacokineticparameterswerecalculatedby3P97programandANOVAwereperformedbySPSS.Results:ThedrugloadingandencapsulationofCyA2CDMwere(23139±0124)%and

6、(91199±2185)%,respectively,andthediameterwas(26017±5101)nm.Theconcentration2timecurveofCyA2CDMR○wasbestfittotwo2opencompartmentsmodel.ComparingwithGengraf,therelativebioavailabilityofCyA2CDMwas97107%,andtherewerenosignificantdifferencesinAUC0236h,tmax,Ka,andMRT0236h(P<

7、0105)exceptthehighercmax(P<0105).Conclusion:CyA2CDMcouldeffectivelyencapsulateCyA,increasetheoverallaqueoussolubilityofR○CyA,andshowtheequivalentbioavailabilitytothatofGengraf.KeywordscyclosporineA;micelles;N2octyl2O2sulfatechitosan;oralbioavailabilityThisstudywassuppo

8、rtedbytheInternationalScienceandTechnologyResarchCooperationProgarmoftheMinistryofScienceandTechnologyofChina(No.2005