90plus纳米粒度仪应用案例
文献名：surfactant–polymernanoparticlesovercomep-glycoprotein-mediateddrugefflux
作者：maheshd.chavanpatil,aymankhdair,brigittegerard,corbinbachmeier,donaldw.miller,malathyp.v.shekharandjayanthpanyam
departmentofpharmaceuticalsciences,eugeneapplebaumcollegeofpharmacyandhealthsciences,waynestateuniversity,detroit,michigan48201,breastcancerprogram,karmanoscancerinstitute,110eastwarrenavenue,detroit,michigan48201,departmentofpharmaceuticalsciences,collegeofpharmacy,universityofnebraskamedicalcenter,omaha,nebraska68198-6025,departmentofpharmacologyandtherapeutics,universityofmanitoba,winnipeg,mb,r3e0t6canada,anddepartmentofpathology,waynestateuniversityschoolofmedicine,detroit,michigan48201
摘要：nanoparticlesenhancethetherapeuticefficacyofanencapsulateddrugbyincreasingandsustainingthedeliveryofthedruginsidethecell.wehavepreviouslydemonstratedthataerosolot(aot)–alginatenanoparticles,anovelformulationdevelopedrecentlyinourlaboratory,significantlyenhancethetherapeuticefficacyofencapsulateddrugslikedoxorubicinindrug-sensitivetumorcells.thepurposeofthisstudyistoevaluatethedrugdeliverypotentialofaot–alginatenanoparticlesindrug-resistantcellsoverexpressingthedrugeffluxtransporter,p-glycoprotein(p-gp).aot–alginatenanoparticleswereformulatedusinganemulsion–cross-linkingprocess.rhodamine123anddoxorubicinwereusedasmodelp-gpsubstrates.cytotoxicityofnanoparticle-encapsulateddoxorubicinandkineticsofnanoparticle-mediatedcellulardrugdeliverywereevaluatedinbothdrug-sensitiveand-resistantcelllines.aot–alginatenanoparticlesenhancedthecytotoxicityofdoxorubicinsignificantlyindrug-resistantcells.theenhancementincytotoxicitywithnanoparticleswassustainedoveraperiodof10days.uptakestudieswithrhodamine-loadednanoparticlesindicatedthatnanoparticlessignificantlyincreasedthelevelofdrugaccumulationinresistantcellsatnanoparticledoseshigherthan200µg/ml.blanknanoparticlesalsoimprovedrhodamineaccumulationindrug-resistantcellsinadose-dependentmanner.nanoparticle-mediatedenhancementinrhodamineaccumulationwasnotbecauseofmembranepermeabilization.fluorescencemicroscopystudiesdemonstratedthatnanoparticle-encapsulateddoxorubicinwaspredominantlylocalizedintheperinuclearvesiclesandtoalesserextentinthenucleus,whereasfreedoxorubicinaccumulatedmainlyinperipheralendocyticvesicles.inhibitionofp-gp-mediatedrhodamineeffluxwithaot–alginatenanoparticleswasconfirmedinprimarybrainmicrovesselendothelialcells.inconclusion,anaot–alginatenanoparticlesystemenhancedthecellulardeliveryandtherapeuticefficacyofp-gpsubstratesinp-gp-overexpressingcells.