PLGA微球载药量和包封率的影响因素及控制-孙美丽

PLGA1．/510006PLGA。PLGAPLGAPLGA、、、PLGA。R94Adoi10．3969/j．issn．1006-8783．2011．06．0231006-8783201106-0643-06ControlofencapsulationefficiencyanddrugloadinginPLGAmicrosphereSUNMei-liBANJun-fengHUANGSi-yuLüZhu-fenInstituteofMaterialMedica/GuangdongProvincialKeyLaboratoryofAdvancedDrugDeliveryGuangdongPharmaceuticalCollegeGuangzhou510006ChinaAbstractPolyDL-lactide-co-glycolidePLGAhasattractedmuchattentionduetoitsgoodbiodegradableandbiocompatibleproperties．PLGAhasbeenshowngreatclinicalapplicationofcontrolleddrugdeliverysystems．FocusingonthelowdrugloadingandencapsulationefficiencyofPLGAmicrospheresthisarticlereviewsthevariablesinfluencingthedrugloadingandencapsulationefficiencywhichmayhavesignificantimplicationsfortheresearchonthedrugloadingandencapsulationefficiency．KeywordsPLGAmicrosph[e-mail]@163．com。2011-10-281122http//．cnki．net/kcms/detail/44．1413．R．20111028．1122．003．htmlPLGA。、FDA81SFDA20092。。PLGAPLGA。1PLGAPLGA、、、-。PLGA、。-JournalofGuangdongPharmaceuticalUniversityDec．2011276、、-。2PLGA、、、。2．1PLGA2．1．1PLGAPLGA/LA/GAPLGA。Makino2PLGAPLGALA/GAPLGAPLGA。3。4PLGAPLGA。5W/O/OPLGA1610014050046%93%PLGA。PLGALA/GA。Du6W/O/WLXT-101PLGALA/GA75∶25mol/mol40∶60mol/mol74．7%55．8%。GAPLGA。PLGA。PLGAPLGA、PEG。PLGAPLGA。Sirsi7--PLGAPLGA100%PLGA。Blanco-Prieto8-VapreotideSirsiPLGA46%87%。PLGA。2．1．2PLGAPLGA。3①9②10③11。Cho12PLGA。9O/OPLGAPLGA。13W/O/WBSA-PLGAPLGA。Mao14O/WAtrasentanPLGA30%PLGA。10PLGAPLGA25%PLGA。2．1．3PLGAPLGA。LA/GA、、PLGAPLGA15。16PLGALA/GAPLGA。PLGAFrauke17PLGAPVALPVAL-g-PLGAW/O/W、、C。PLGA18。2．22．2．1。O/WO/OW/O/OW/O/W。4462719W/O/W、S/O/W、O/O/W80%、60%25%。Thote20O/W96%W/O/O/O/41%。Wischke21、THFO/WAPLGA。S/O/W。、。、22。2．2．2。Eslami235%20%100%80%。Elkheshen24。Zaghloul25-β--PLGA85/153∶1。2．2．3。PLGAPLGA15。Elkheshen24DSCIRPLGA。PLGA3。Su26PLGAPLGA75257EPLGA75257E。2．2．4。。Gupte2790%。W/O/W①pH、。pHpH。Srinivasan22PLGApH76%。②Zn。Aguiar28W/O/W--β-14．76%。Manoharan29W/O/W85．5%。2．3、。2．3．1。、、、、。Ravi30W/O/WBSA、、40．14%、29．93%、29．57%。。PLGA。PLGA。。、PLGA、PLGA。。Castellanos31S/O/Wα-5466．PLGA。Cho12。。、、、32。33。2．3．2。/14。。Zhang34BSA。2mL10mL78．6%99．0%。。Deng35O/W5-5-HMT-1∶501∶20011.79%。。36。BSA37。Singh38STP。Parikh39W/O/W5-PLGA。、、、、。2．3．3。-。。40。Teng355-HMT20℃50℃70．44%24．07%。PLGAPLGA5-HMT。2．4PLGA。PLGA。、、20、80、F68HSA、PEG、-β-HP-β-CD9313741－44。/22、80、80、PVA。。6。Mao14PVAPVAPVAPVA。Gupta451PGE11HP-β-CD。2PGE1HP-β-CD。。3PLGA。PLGA64627。PLGAPLGAPLGAPLGAPLGA/。。1．J．DrugEvalRes2010335332－334．2MAKINOKNAKAJIMATSHIKAMURAMetal．Efficientintracellulardeliveryofrifampicintoalveolarmacrophagesusingrifampicin-loadedPLGAmicrosphereseffectsofmolecularweightandcompositionofPLGAonreleaseofrifampicinJ．ColloidsSurfBBiointerfaces20046135－42．3HAMISHEHKARHEMAMIJNAJAFABADIARetal．Theeffectofformulationvariablesonthecharacteristicsofinsulin-loadedpolylactic-co-glycolicacidmicrospherespreparedbyasinglephaseoilinoilsolventevaporationmethodJ．ColloidsSurfBBiointerfaces2009741340－349．4．_J．200718128－41．5WUJin-huiWULinXUXiao-qiangetal．Microspheresmadebyw/o/oemulsionmethodwithreducedinitialburstforlong-termdeliveryofendostaranovelrecombinanthumanendostatinJ．JPharmSci20099862051－2058．6DULi-naCHENGJun-pingCHIQiangetal．BiodegradablePLGAmicrospheresasasustainedreleasesystemforanewluteinizinghormone-releasinghormoneLHRHantagonistJ．ChemPharmBull20065491259－1265．7SIRSISRSCHRAYRCWHEATLEYMAetal．Formulationofpolylactide-co-glycolicacidnanospheresforencapsulationandsustainedreleaseofpolyethyleneimine-polyethyleneglycolcopolymerscomplexedtooligonucleotidesJ．JNanobiotechnol200971．8BLANCO-PRIETOMJCAMPANEROMABESSEGHIRKetal．ImportanceofsingleorblendedpolymertypesforcontrolledinvitroreleaseandplasmalevelsofasomatostatinanalogueentrappedinPLA/PLGAmicrospheresJ．JControlRelease2004963437－448．9．－J．200622119－24．10．PLGAJ．2011462124－127．11MAURYASDDHAKARRCAGGARAWALS．DesignandevaluationofSRMmicrosphereofmetforminhydrochlorideJ．PharmacieGlobaleIJCP2010171－5．12CHOMSAHH．FormulationandprocessparametersaffectingproteinencapsulationintoPLGAmicrospheresduringethylacetate-basedmicroencapsulationprocessJ．JMicroencapsul20052211－1213．BSA-PLGAJ．200925172935－2938．14MAOSRSHIYLILetal．Effectsofprocessandformulationparametersoncharacteristicsandinternalmorphologyofpolydl-lactide-co-glycolidemicrospheresformedbythesolventevaporationmethodJ．EurJPharmBiopharm2008682214－223．15PANYAMJWILLIAMSDDASHAetal．Solid-statesolubilityinfluencesencapsulationandreleaseofhydrophobicdrugsfromPLGA/PLAnanoparticlesJ．JPharmSci20049371804－1814．16YEOYPARKK．Characterizationofreservoir-typemicrocap-sulesmadebythesolventexchangemethodJ．AAPSPharmSciTech20045410－17．17FRAUKEPKBREITENBACHAZANGEVRetal．Brush-likebranchedbiodegradablepolyesterspartIII．Proteinreleasefrommicrospheresofpolyvinylalcohol-graft-polyDL-lactic-co-glycolicacidJ．JControlRelease20017317－20．18WALTEREDREHERDKOKMetal．HydrophilicpolyDL-lactide-co-glycolidemicrospheresforthedeliveryofDNAtohuman-derivedmacrophagesanddendriticcellsJ．JControlRelease2001761/2149－168．19ANDREASKZEHBERKAZUBEKMetal．Biodegradableinsulin-loadedPLGAmicrospheresfabricatedbythreedifferent