Antibody-Mediated Drug Delivery Systems: Concepts, Technology, and Applications

525 Pages·2011·5.07 MB·English

ANTIBODY-MEDIATED
DRUG DELIVERY SYSTEMS
ANTIBODY-MEDIATED
DRUG DELIVERY SYSTEMS
Concepts, Technology, and Applications
Editedby
YASHWANT PATHAK
DepartmentofPharmaceuticalSciences
CollegeofPharmacy
UniversityofSouthFlorida
Tampa,Florida
SIMON BENITA
TheInstituteforDrugResearchoftheSchoolofPharmacy
TheHebrewUniversityofJerusalem
Jerusalem,Israel
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LibraryofCongressCataloging-in-PublicationData:
Antibody-mediateddrugdeliverysystems:concepts,technology,andapplications/editedby
YashwantPathak,SimonBenita.
p.;cm.
ISBN978-0-470-61281-1(cloth)
I.Pathak,Yashwant.II.Benita,Simon,1947-
[DNLM:1. Antibodies–therapeuticuse.2. DrugDeliverySystems.3. DrugCarriers.4.
Nanoparticles.QV785]
615.37–dc23
2011037603
PrintedintheUnitedStatesofAmerica
10987654321
CONTENTS
CONTRIBUTORS xv
PREFACE xix
CHAPTER1 ANTIBODY-MEDIATEDDRUGDELIVERYSYSTEMS:GENERAL
REVIEWANDAPPLICATIONS
NavdeepKaur,KarthikeyanSubramani,andYashwantPathak 1
1 HistoricalPerspective 1
2 Antibodies 2
2.1 StructureofAntibodies 2
2.2 TypesofAntibodies 2
2.3 AntibodyDevelopment 3
3 AntibodyMediation 3
4 Antibody-Mediated DrugDeliverySystems 4
5 Applications 6
6 RecentTrends 9
7 FutureTrends 10
References 10
CHAPTER2 IMMUNOLIPOSOMESFORCARDIOVASCULARTARGETING
TatyanaLevchenko,WilliamHartner,andVladimirP.Torchilin 13
1 Introduction 13
2 ImmunoliposomeTargetingtoPathologicalRegionsoftheVesselWall 14
3 LiposomeInternalization byEndothelialCells 15
4 TargetingofAtheroscleroticLesionsforTomographicImaging 17
5 Antibody-Mediated LiposomesforDiagnosisofThrombosis 17
6 ThrombolyticTherapywithImmunoliposomes 18
7 TargetedSealingofCellMembraneLesions:PreservationofCellViability 19
8 Accumulation ofLiposomesandImmunoliposomes intheIschemicHeart 21
9 ImmunoliposomesasaDrugandGeneDeliveryVehicle totheInfarctedHeart 26
References 29
CHAPTER3 ANTIBODY-MEDIATEDDRUGDELIVERYSYSTEMSFOR
BREASTCANCERTHERAPEUTICS
LeonorMunozAlcivarandYashwantPathak 35
1 Introduction 35
2 BreastCancer 35
2.1 Statistics 36
2.2 CommonTreatment 36
v
vi CONTENTS
3 DrugDeliverySystems 36
3.1 Features 37
4 MonoclonalAntibodies 37
4.1 AntitumorActivity 38
4.2 Trastuzumab 38
4.3 Bevacizumab 39
4.4 Pertuzumab 40
4.5 Paclitaxel–MonoclonalAntibody 40
5 HumanEpidermalGrowthFactorReceptor2 40
5.1 InhibitorsofEpidermalGrowthFactorReceptor 42
5.2 VascularEndothelialGrowthFactor 42
6 Antibody-Mediated DrugDeliverySystem 43
6.1 Trastuzumab–DM1Conjugate 43
6.2 Anti-HER2Antibody–DrugConjugates 43
6.3 Antibody-BasedTherapeutics 44
7 TargetsfortheTreatmentofBreastCancer 45
8 BreastCancerTherapies 46
8.1 Taxane 46
8.2 Chemotherapy 46
8.3 Antigens 47
8.4 Nicastrin 47
8.5 Erlotinib 48
8.6 HumanArrestDefective 1 48
8.7 HighlyMonodisperseMagnetiteNanocrystals 48
9 TheFutureofBreastCancerTherapeutics 49
10 OtherTreatmentStrategies 50
11 Nanotechnology 51
12 Conclusions 52
References 53
CHAPTER4 DEVELOPMENTOFIMMUNONCONJUGATESFORINVIVO
DELIVERY:CANCERDIAGNOSIS,IMAGING,ANDTHERAPY
ArutselvanNatarajan 57
1 Introduction 57
1.1 Development ofmAbsforSpecificTargets 57
1.2 NakedAntibodies forCancerTherapy 57
2 Immunoconjugates 61
3 Immunoconjugates inCancerTherapy 62
3.1 Radioimmunoconjugates 62
3.2 Pre-targetedTherapy 63
3.3 Antibody–DrugConjugate 64
3.4 Antibody–ToxinConjugate 66
3.5 Antibody–siRNAconjugate 68
3.6 Antibody–CytokineConjugate 68
3.7 AntiproliferativeConjugates 68
3.8 Immunoconjugates withpH-Activatable Probe 69
4 Immunoconjugates forImaging 69
4.1 Immuno-SPECT 69
4.2 Immuno-PET 70
CONTENTS vii
5 Immunoconjugates inDiagnosticApplications 71
6 Immunoconjugates’PromisingFutureandChallenges 72
7 Summary 73
References 73
CHAPTER5 MATHEMATICALMODELSOFANTI-TNFTHERAPIES
ANDTHEIRCORRELATIONWITHTUBERCULOSIS
SimeoneMarino,MohammadFallahi-Sichani,
JenniferJ.Linderman,andDeniseE.Kirschner 83
1 Introduction 83
2 Tuberculosis,TNF,andAnti-TNFDrugs 84
2.1 EpidemiologyofTuberculosis 84
2.2 TBImmunologyandtheRoleofTNF 85
2.3 TNFBiology 85
2.4 Anti-TNFDrugs 87
3 TheoreticalModelsToStudyTBInfection 88
3.1 ODEModel:TBReactivation BasedonTNFBioavailabilityandFraction
ofTNFThatIsSolublevs.Membrane-BoundFraction 89
3.2 PDEModel:TNFReceptorDynamics andCellularOrganization
inaTuberculosisGranuloma 91
4 PresentandFutureWork 96
References 98
CHAPTER6 TARGETEDNANOPARTICLESINRADIOTHERAPY
MistyMuscarellaandYashwantPathak 105
1 Introduction 105
2 Nanoparticles 106
2.1 NanoparticleTechnology 106
2.2 NanoparticleCompositionsandFunctions forCancerTherapy 106
2.3 Nanotechnology Advantages inCancerTherapy 107
2.4 NanoparticleDeliverySystems 107
2.5 RoleofMonoclonalAntibodies inSpecificity 108
2.6 Drug-EncapsulatedHollowProteinNanoparticles 108
2.7 TargetingbyNanoparticles 109
3 Radiotherapy 110
3.1 Drawbacks toRadiotherapy 110
3.2 Radioimmunotherapy 111
4 Nanoparticles inRadiotherapy 111
4.1 RadiolabeledNanoparticles forAntiangiogenesis Therapy 112
4.2 RadiolabeledNanoparticles forImaging 112
4.3 RoleofNanoparticles inRadioimmunotherapy 113
4.4 Nanotargeted RadionuclidesforCancerTherapyandImaging 113
4.5 ModifyingNanocarriers 114
4.6 CarbonNanotubes inRadiationTherapyandImaging 115
4.7 CarbonNanotubes inMicroradiotherapy 116
4.8 GoldNanoparticle RadiationTherapy 116
4.9 EnhancementofRadiationTherapybyGoldNanoparticles 117
viii CONTENTS
4.10 NoninvasiveRFHyperthermia 118
4.11 EnhancementofRadiosensitivitybyNanoparticles 119
4.12 Nanoparticle-Enhanced MRI 121
4.13 ProtectionProvidedbyMelanin-CoveredNanoparticles 121
4.14 ImmunotoxicityofNanoparticles 122
5 CurrentandFutureDevelopments withNanotechnology inRadiotherapy 123
5.1 RFField-InducedThermalCytotoxicityinCancerCellsTreatedwith
FlorescentNanoparticles 123
5.2 SusceptiblilityofPancreatic CarcinomaCellsNoninvasiveRFFieldsafter
TreatmentwithTargetedGoldNanoparticles 123
6 Conclusions 124
References 124
CHAPTER7 ELECTRICALLY-ENHANCEDDELIVERYOFDRUGSAND
CONJUGATESFORCANCERTREATMENT
ArutselvanNatarajan,LucaCampana,andRajiSundararajan 129
1 Introduction 129
2 ElectroporationMechanismstoPermeabilize theDrugsandDNAs inCells 130
2.1 RoleofExternalElectricalPulsesandElectrostaticForcesonLiveCells 132
3 Electroporation-Aided DrugDeliveryforPreclinicalStudies 133
3.1 Electrochemotherapy 136
4 EPapplications forHumanPatientStudies 136
4.1 Electrochemotherapy forChestWallCarcinoma 136
5 FuturePerspectives 138
6 Summary 139
References 140
CHAPTER8 CHARACTERIZATIONOFMONOCLONALANTIBODYVARIANTS
ANDGLYCOSYLATION
TingZheng,SrinivasaRao,JeffRohrer,andChrisPohl 145
1 Characterization ofMonoclonalAntibodyHeterogeneitybyHPLCAnalysis 145
1.1 CharacterizationUsingHydrophobic-Interaction Chromatography 146
1.2 CharacterizationUsingSize-ExclusionChromatography 147
1.3 CharacterizationUsingCation-ExchangeColumns 148
2 AnalysisofMonoclonalAntibodyGlycosylation 150
2.1 MAbMonosaccharideCompositionalAnalysis 151
2.2 MAbSialicAcidCompositionalAnalysis 153
2.3 MAbN-GlycanAnalysis 157
References 163
CHAPTER9 ANTIBODY-MEDIATEDDRUGDELIVERYSYSTEMFOR
LYMPHATICTARGETINGTREATMENT
FangWu,HongDing,andZhirongZhang 169
1 Introduction 169
2 LymphaticDisordersandTheirNormalTreatment 170
2.1 Lymphoma 170
CONTENTS ix
2.2 AcuteandChronicLymphocytic Leukemia 171
2.3 Lymphedema 172
3 Antibody-Mediated DrugDeliverySystemsforLymphaticTargetingTreatment 172
3.1 Antibody–DrugConjugates 172
3.2 ImmunotoxinasanAntibody-MediatedDDS 176
3.3 Polymer–AntibodyConjugates 178
3.4 Antibody-ConjugatedLiposomes 181
3.5 OtherAntibody-Mediated DeliveryStrategies 182
4 ConclusionsandFuturePerspectives 183
References 184
CHAPTER10 METHODSFORNANOPARTICLECONJUGATIONTO
MONOCLONALANTIBODIES
JunlingLiandChinK.Ng 191
1 Introduction 191
2 CurrentNanoparticle SystemsusedforConjugationwithmAbs 191
3 ConjugationMethods 192
3.1 AdsorptionBinding 192
3.2 CovalentBinding 192
4 Conclusions 202
References 202
CHAPTER11 SINGLE-USESYSTEMSINANIMALCELL–BASED
BIOPRODUCTION
WilliamG.Whitford 209
1 Introduction 209
2 ComponentOfferings 214
2.1 BioprocessContainers 215
2.2 Single-UseMixers 216
2.3 Single-UseBioreactors 216
2.4 DownstreamApplications 217
3 CharacteristicsofSingle-UseSystemsandTheirApplications 218
3.1 CostandFinance Advantages 218
3.2 MaterialsAcceptability 219
3.3 TechnicalTransferandScale-up 220
3.4 ProductsandPlatformsSupported 220
3.5 RegulatoryRequirements 220
3.6 Probes,Sensors,andSampling 221
3.7 CouplingandTransfer 221
3.8 EnvironmentalFootprint 221
3.9 Flexibility 222
3.10 Performance 222
3.11 QbDandPAT 224
3.12 Scalability 225
3.13 ModularityandReconfigurablity 225
3.14 AutomationAmenability 225
3.15 ImprovedComplianceValues 226
References 226
x CONTENTS
CHAPTER12 IMMUNOLIPOSOMESFORSPECIFICDRUGDELIVERY
ManuelaCalin 229
1 Introduction:Advances inLiposomeFormulation 229
2 DesignofImmunoliposomesforSite-SpecificDrugDelivery 230
2.1 ImmunoliposomePreparation 231
2.2 TypesofImmunoliposomes 237
3 Cellular-SpecificTargetingofImmunoliposomes 242
3.1 InVitroTargetingofImmunoliposomes 242
3.2 InVivoApplications ofImmunoliposomes 243
4 Cellular-SpecificInternalizationofImmunoliposomes 246
5 Immunoliposomes inDiagnosisandTherapy 247
5.1 TargetedDeliveryofImagingAgents withImmunoliposomes 247
5.2 UseofImmunoliposomesinOncology 248
5.3 UseofImmunoliposomesinInfectiousDiseases 249
5.4 UseofImmunoliposomesinInflammation-Related Diseases 250
5.5 UseofImmunoliposomesinDrugDeliverytotheBrain 251
5.6 UseofImmunoliposomesinTargetedGene Delivery 251
6 ClinicalUseofImmunoliposomes 251
7 ConclusionsandPerspectives 252
References 253
CHAPTER13 GENETHERAPYTARGETINGKIDNEYDISEASES:ROUTESAND
VEHICLES
YoshitakaIsaka,YoshitsuguTakabatake,andHiromiRakugi 267
1 Introduction 267
2 RationaleforSuccessfulGeneTargeting 268
3 Site-SpecificGeneDelivery 268
4 Nuclear ImportofGene Material 270
5 TargetingtheGlomerulus 270
6 TargetingtheTubule 272
7 TargetingtheInterstitium 274
8 TargetingMuscle 274
9 Conclusions 275
References 275
CHAPTER14 DETECTIONOFANTIBODIESTOPOLY(ETHYLENEGLYCOL)
POLYMERSUSINGDOUBLE-ANTIGEN-BRIDGING
IMMUNOGENICITYELISA
YijuanLiu,HelenReidler,JingPan,DavidMilunic,DujieQin,
DaveChen,YliRemoVallejo,andRayYin 279
1 Introduction 279
2 Methods 280
2.1 Materials 280
2.2 ELISAMethodOptimization 280
2.3 ELISAProcedures 281
2.4 AssayReproducibility 282
2.5 DrugToleranceTestingandFreeDrugDepletionAssays 282
CONTENTS xi
2.6 ScreeningCutPointwithNormalHumanSerumSamples 282
2.7 DeterminationofAntibodySpecificityinPositiveHuman
SerumSamples 282
2.8 DeterminationofSampleMatrixEffects 283
3 Results 283
3.1 Dose–ResponseCurvesandAssayReproducibility 283
3.2 DrugToleranceTestingandFreeDrugDepletionAssays 283
3.3 ScreeningCut-PointDetermination withNormalHumanSerumSamples 285
3.4 DeterminationofAntibodySpecificityinPositiveHumanSerumSamples 286
3.5 SampleMatrixEffects 286
4 Discussion 286
References 289
CHAPTER15 ANTIBODIESINNANOMEDICINEANDMICROIMAGING
METHODS
RakeshSharma 291
1 Introduction:AntibodyMoleculesandNanoparticles 291
2 Antibody-BasedNanoparticles inMicroimaging 292
2.1 21-TMRMicroimaging 292
2.2 Nanoparticles 293
2.3 PreparationofNanoparticle CompositesinMicroimaging 297
2.4 Nanoparticle-BasedMagneticResonanceMicroimaging 302
2.5 Three-DimensionalReconstruction 308
3 TroponinT:NewerMagneticImmunoassayMethod 317
3.1 TroponinsasPoint-of-CareDetectionofAcuteMyocardialInfarction 317
3.2 UseofaPenlikeAMIDetectable Device 322
3.3 MALDIAnalysisofTroponin 328
3.4 LimitationsofTroponinDetectionMethods 330
3.5 Feasibility 330
4 GoldNanoparticles asanAntigen CarrierandAdjuvant 330
4.1 HeptenAntigensandImmuneResponse 330
4.2 AdjuvantPropertiesofGoldNanoparticles 332
4.3 ImmunomodulationbyColloidalGoldNanoparticles 334
4.4 LimitationsofGoldParticleMethods 337
4.5 FeasibilityofUsingGoldParticles 338
5 Immunochemical Biosensors,Nanomedicine, andDisease 339
5.1 NanobiosensorsinNanomedicine 339
5.2 AntibodiesinNanorobots 339
6 FutureDirections andConclusions 341
References 341
CHAPTER16 METHODSFORPOLYMERICNANOPARTICLECONJUGATION
TOMONOCLONALANTIBODIES
UyenMinhLe,HieuTran,andYashwantPathak 351
1 Introduction 351
1.1 PolymericNanoparticles 351
1.2 ProcedureforConjugationofmAbtoPolymericNanoparticles 351
2 ConjugationofmAbandPolyethylenimine Nanoparticles 353