专业外语教学（吉林大学）-manuscript for plga microparticles

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1、Combinationofdoxorubicin-basedchemotherapyandpolyethylenimine/p53genetherapyforthetreatmentoflungcancerusingporousPLGAmicroparticlesXiaozhengShia,c,ChunjieLia,c,SaiGaoa,c,LingfeiZhanga,c,HaoboHana,c,JianxuZhanga,c,WeiShia,b,c,*,QuanshunLia,b,c,*aKeyL

2、aboratoryforMolecularEnzymologyandEngineering,theMinistryofEducation,JilinUniversity,Changchun130012,ChinabNationalEngineeringLaboratoryforAIDSVaccine,JilinUniversity,Changchun130012,ChinacSchoolofLifeSciences,JilinUniversity,Changchun130012,China*Co

3、rrespondingauthor.Tel.:+86-431-85155216;Fax:+86-431-85155200.E-mailaddress:quanshun@jlu.edu.cn(Q.Li);shiw@jlu.edu.cn(W.Shi).20AbstractInthisstudy,porousPLGAmicroparticlesfortheco-deliveryofdoxorubicinandPEI25K/p53weresuccessfullypreparedbythewater-oi

4、l-wateremulsionsolventevaporationmethod,usingammoniumbicarbonateasaporogen.Theporousmicroparticleswereobtainedwithameandiameterof22.9±11.8μmasdeterminedbylaserscatteringparticlesizeanalysis.Theparticles’surfaceporousmorphologyanddistributionsofdoxor

5、ubicinandp53weresystematicallycharacterizedbyscanningelectronmicroscopy,flowcytometry,fluorescencemicroscopyandconfocallaserscanningmicroscopy,revealingthatdoxorubicinandtheplasmidweresuccessfullyco-encapsulated.Encapsulationefficienciesof88.2±1.7%an

6、d36.5±7.5%wereachievedfordoxorubicinandtheplasmid,respectively,demonstratingthattheporousstructuredidnotadverselyaffectpayloadencapsulation.MicroparticlesharboringbothdoxorubicinandPEI25K/p53exhibitedenhancedtumorgrowthinhibitionandapoptosisinduction

7、comparedtothoseloadedwitheitheragentaloneinA549humanlungadenocarcinomacells.Overall,theporousPLGAmicroparticlesprovideapromisinganticancerdeliverysystemforcombinedchemotherapyandgenetherapy,andhavegreatpotentialasatoolforsustainedlocaldrugdeliverybyi

8、nhalation.Keywords:Porousmicroparticles;PLGA;Co-delivery;Doxorubicin;p53gene201.IntroductionLungcancerisaleadingcauseofmalignancy-relateddeathinbothdevelopinganddevelopedcountries[1,2].Theprimarytreatmentchoicesforpatientswithlungcancerareconventiona