Targeted Drug Delivery

449 Pages·2023·10.758 MB·english

by  Bachhav Y. (ed.)

TargetedDrugDelivery
MethodsandPrinciplesinMedicinalChemistry
Editedby
R.Mannhold,H.Buschmann,J.Holenz
EditorialBoard
G.Folkers,H.Timmermann,H.vandeWaterbeemd,J.BondoHansen
PreviousVolumesoftheSeries
Bachhav,Y.(Ed.)
Alza,E.(Ed.)
InnovativeDosageFormsDesign
FlowandMicroreactorTechnology
andDevelopmentatEarlyStage
inMedicinalChemistry
2019
2022
ISBN:978-3-527-34396-6
ISBN:978-3-527-34689-9
Vol.76
Vol.81
Gervasio,F.L.,Spiwok,V.(Eds.)
Rübsamen-Schaeff,H.,andBuschmann,H.
(Eds.) BiomolecularSimulationsin
NewDrugDevelopmentforKnown Structure-basedDrugDiscovery
andEmergingViruses
2018
ISBN:978-3-527-34265-5
2022
Vol.75
ISBN:978-3-527-34337-9
Vol.80
Sippl,W.,Jung,M.(Eds.)
Gruss,M.(Ed.) EpigeneticDrugDiscovery
SolidStateDevelopmentand
2018
ProcessingofPharmaceutical
ISBN:978-3-527-34314-0
Molecules Vol.74
Salts,Cocrystals,andPolymorphism
Giordanetto,F.(Ed.)
2021
EarlyDrugDevelopment
ISBN:978-3-527-34635-6
Vol.79
2018
ISBN:978-3-527-34149-8
Plowright,A.T.(Ed.)
Vol.73
TargetDiscoveryandValidation
MethodsandStrategiesforDrug Handler,N.,Buschmann,H.(Eds.)
Discovery DrugSelectivity
2020 2017
ISBN:978-3-527-34529-8 ISBN:978-3-527-33538-1
Vol.78 Vol.72
Swinney,D.,Pollastri,M.(Eds.)
NeglectedTropicalDiseasesDrug
DiscoveryandDevelopment
2019
ISBN:978-3-527-34304-1
Vol.77
Targeted Drug Delivery
Edited by
Yogeshwar Bachhav
Series Editors
Raimund Mannhold
Helmut Buschmann
Jörg Holenz
Editor AllbookspublishedbyWILEY-VCHarecarefully
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v
Contents
APersonalForeword xiii
Preface xv
1 BasicsofTargetedDrugDelivery 1
KshamaA.Doshi
1.1 Introduction 1
1.1.1 ConceptofBioavailabilityandTherapeuticIndex 2
1.2 TargetedDrugDelivery 2
1.3 StrategiesforDrugTargeting 3
1.3.1 PassiveTargeting 4
1.3.1.1 ReticuloendothelialSystem(RES)System 4
1.3.1.2 EnhancedPermeabilityandRetention(EPR)Effect 4
1.3.1.3 LocalizedDelivery 4
1.3.2 ActiveTargeting 5
1.3.3 PhysicalTargeting 5
1.3.3.1 UltrasoundforTargeting 6
1.3.3.2 MagneticFieldforTargeting 6
1.4 TherapeuticApplicationsofTargetedDrugDelivery 6
1.4.1 DiabetesManagement 6
1.4.2 NeurologicalDiseases 7
1.4.3 CardiovascularDiseases 8
1.4.4 RespiratoryDiseases 9
1.4.5 CancerIndications 9
1.5 TargetedDug-DeliveryProducts 10
1.6 Challenges 11
1.6.1 PassiveTargetingandEPREffect 12
1.6.2 ActiveTargeting 12
1.7 Scale-upandChallenges 13
1.8 CurrentStatus 14
1.9 ConclusionandProspects 15
References 16
vi Contents
2 AddressingUnmetMedicalNeedsUsingTargeted
Drug-DeliverySystems:EmphasisonNanomedicine-Based
Applications 21
ChandrakantsingPardeshi,RajuSonawane,andYogeshwarBachhav
2.1 Introduction 21
2.2 TargetedDrug-DeliverySystemsforUnmetMedicalNeeds 23
2.2.1 TargetingLigands 25
2.2.1.1 SmallMoleculesasTargetingLigands 25
2.2.1.2 AptamersasTargetingLigands 27
2.2.1.3 AntibodiesasTargetingLigands 28
2.2.1.4 LectinsasTargetingLigands 28
2.2.1.5 LactoferrinsasTargetingLigands 29
2.2.2 TargetingApproaches 29
2.2.2.1 Disease-BasedTargeting 29
2.2.2.2 Location-BasedTargeting 32
2.3 RegulatoryAspectsandClinicalPerspectives 35
2.4 ConclusionandFutureOutlook 38
ListofAbbreviations 38
References 39
3 Nanocarriers-BasedTargetedDrugDeliverySystems:Small
andMacromolecules 45
PreshitaDesai
3.1 Nanocarriers(Nanomedicine)–OverviewandRoleinTargetedDrug
Delivery 45
3.2 PassiveTargetingApproaches 50
3.2.1 EnhancedPermeabilityandRetention-Effect-BasedTargeting 50
3.3 ActiveTargetingApproaches 52
3.4 StimuliResponsiveTargetedNCs 54
3.4.1 RedoxStimuliResponsiveTargetedNCs 55
3.4.2 pHStimuliResponsiveTargetedNCs 56
3.4.3 EnzymeStimuliResponsiveTargetedNCs 57
3.4.4 TemperatureStimuliResponsiveTargetedNCs 58
3.4.5 UltrasoundStimuliResponsiveTargetedNCs 59
3.4.6 MagneticFieldStimuliResponsiveTargetedNCs 59
3.5 ConclusionandFutureProspects 60
References 60
4 LiposomesasTargetedDrug-DeliverySystems 69
RaghavendraC.Mundargi,NeetikaTaneja,JayeshkumarJ.Hadia,and
AjayJ.Khopade
4.1 Introduction 69
4.2 LiposomeCommercialLandscape 72
4.3 ImportantConsiderationsinDevelopmentandCharacterizationof
Liposomes 80
Contents vii
4.3.1 SelectionofLipids 80
4.3.2 Drug:LipidRatio 81
4.3.3 PEGylation 82
4.3.4 LigandAnchoring 83
4.3.5 Drug-LoadingTechniques 84
4.3.6 PhysicochemicalCharacterization 85
4.3.7 ManufacturingProcess 86
4.3.8 ProductStability 87
4.4 TargetedDeliveryofLiposomes 88
4.4.1 PassiveTargeting 89
4.4.2 Active-TargetedDelivery 92
4.4.2.1 CancerCellTargeting 94
4.4.2.2 TumorEndotheliumTargeting 98
4.5 RecentClinicalTrialswithLiposomeswithInvestigationalLiposome
Candidates 102
4.6 FactorsInfluencingtheClinicalTranslationofLiposomesforTargeted
Delivery 103
4.7 ConclusionsandFutureofProspectsofTargetedLiposomal-Delivery
Systems 108
ListofAbbreviations 110
References 112
5 Antibody–DrugConjugates:Developmentand
Applications 127
RajeshPradhan,MeghnaPandey,SiddhanthHejmady,RajeevTaliyan,
GautamSinghvi,SunilK.Dubey,andSachinDubey
5.1 Introduction 127
5.2 DesignofADCs 128
5.2.1 Antibody 129
5.2.2 Linker 130
5.2.3 Payload 132
5.3 MechanismofAction 133
5.4 PharmacokineticConsiderationsforADCs 134
5.4.1 HeterogeneityofADCs 134
5.4.2 BioanalyticalConsiderationsforADCs 135
5.4.3 PharmacokineticParametersofADCs 136
5.4.3.1 Absorption 136
5.4.3.2 Distribution 136
5.4.3.3 MetabolismandElimination 136
5.5 ApplicationsofADCs 137
5.5.1 ApprovedADCsintheMarket 137
5.5.1.1 GemtuzumabOzogamicin 137
5.5.1.2 BrentuximabVedotin 139
5.5.1.3 Ado-TrastuzumabEmtansine(T-DM1) 139
5.5.1.4 InotuzumabOzogamicin 139
viii Contents
5.5.1.5 PolatuzumabVedotin-piiq 140
5.5.1.6 EnfortumabVedotin 140
5.5.1.7 TrastuzumabDeruxtecan 140
5.5.2 UseofADCsinRheumatoidArthritis 141
5.5.3 UseofADCsinBacterialInfections 141
5.5.4 UseofADCsinOphthalmology 141
5.6 ResistanceofADC 142
5.7 RegulatoryAspectsforADCs 143
5.7.1 RoleofONDQA 143
5.7.2 RoleofOBP 144
5.8 ConclusionandFutureDirection 144
References 145
6 Gene-DirectedEnzyme–ProdrugTherapy(GDEPT)asaSuicide
GeneTherapyModalityforCancerTreatment 155
PrashantS.KharkarandAtulL.Jadhav
6.1 Introduction 155
6.2 GDEPTforDifficult-to-TreatCancers 159
6.2.1 High-GradeGliomas(HGGs) 159
6.2.2 Triple-NegativeBreastCancer(TNBC) 161
6.2.3 OtherCancers 162
6.3 NovelEnzymesforGDEPT 164
6.4 Conclusions 165
References 165
7 TargetedProdrugsinOralDrugDelivery 169
MilicaMarkovic,ShimonBen-Shabat,andArikDahan
7.1 Introduction 169
7.1.1 Classicvs.ModernProdrugApproach 170
7.2 Modern,TargetedProdrugApproach 171
7.2.1 ProdrugApproach-TargetingEnzymes 171
7.2.1.1 Valacyclovirase-MediatedProdrugActivation 172
7.2.1.2 PhospholipaseA -MediatedProdrugActivation 173
2
7.2.1.3 Antibody,Gene,andVirus-DirectedEnzyme–Prodrug
Therapy 175
7.2.2 ProdrugApproachTargetingTransporters 176
7.2.2.1 PeptideTransporter1 177
7.2.2.2 MonocarboxylateTransporterType1 179
7.2.2.3 BileAcidTransporters 180
7.3 ComputationalApproachesinTargetedProdrugDesign 181
7.4 Discussion 182
7.5 FutureProspectsandClinicalApplications 183
7.6 Conclusion 183
References 184
Contents ix
8 ExosomesforDrugDeliveryApplicationsinCancerand
CardiacIndications 193
AnjaliPandya,SreeranjiniPulakkat,andVandanaPatravale
8.1 ExtracellularVesicles:AnOverview 193
8.1.1 EvolutionofExosomes 194
8.1.2 ExosomesasDeliveryVehiclesforTherapeutics 195
8.1.2.1 EndogenousLoadingMethods 198
8.1.2.2 ExogenousLoadingMethods 198
8.2 ExosomesasCancerTherapeutics 199
8.2.1 InfluenceofDonorCells 202
8.2.2 DifferentTherapeuticCargoExploredinCancerTherapy 202
8.2.2.1 DeliveryofProteinsandPeptides 203
8.2.2.2 DeliveryofChemotherapeuticCargo 204
8.2.2.3 DeliveryofRNA 204
8.3 ExosomeBasedDrugDeliveryforCardiovascularDiseases 206
8.3.1 DeliveryofCardioprotectiveRNAs 207
8.3.2 ExosomesModifiedwithCardiacTargetingPeptides 208
8.4 ClinicalEvaluationsandFutureAspects 210
8.5 Conclusion 211
Acknowledgments 212
References 212
9 DeliveryofNucleicAcids,SuchassiRNAandmRNA,Using
ComplexFormulations 221
AnanyaPattnaik,SwarnaparabhaPany,A.S.Sanket,SudipteeDas,
SanghamitraPati,andSangramK.Samal
9.1 Introduction 221
9.2 NA-BasedComplexDeliverySystem 228
9.2.1 ClassicalNA-BasedComplexDeliverySystem 229
9.2.1.1 Polymer-BasedNA-ComplexDeliverySystem 229
9.2.1.2 Lipid-BasedComplexNADeliverySystem 230
9.2.1.3 Peptide-BasedComplexNADeliverySystem 231
9.2.2 AdvancedNA-BasedComplexDeliverySystems 232
9.2.2.1 InorganicandHybridNPs 232
9.2.2.2 Self-AssembledNANanostructures 233
9.2.2.3 ExosomesandNanoCells 233
9.3 ApplicationsofNA-ComplexDeliverySystems 234
9.3.1 GenomeEditing 235
9.3.2 CancerTherapy 237
9.3.3 ProteinTherapy 238
9.4 FutureProspective 239
9.5 Conclusion 240
Acknowledgments 240
References 240