Drug Targeting Organ-Specific Strategies

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XXVI Contents 13.3.1.3 Release or Activation of D at the Target Site . . . . . . . . 353 13.3.1.4 Removal of D from the Target Site . . . . . . . . . . . . . . 354 13.3.1.5 Release of D at Non-target Sites . . . . . . . . . . . . . . . 355 13.3.1.6 Disposition of D . . . . . . . . . . . . . . . . . . . . . . . . 355 13.3.2 Model of Hunt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355 13.3.3 Model of Boddy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357 13.3.4 Model of Rowland and McLachlan . . . . . . . . . . . . . . . . . . . 357 13.4 Measures of Effectiveness of Drug Targeting . . . . . . . . . . . . . . . . . . 357 13.4.1 Therapeutic Availability (TA) . . . . . . . . . . . . . . . . . . . . . . 358 13.4.2 Drug Targeting Index (DTI) . . . . . . . . . . . . . . . . . . . . . . . 358 13.4.3 Targeting Index (TI) . . . . . . . . . . . . . . . . . . . . . . . . . . . 359 13.5 Evaluation of Effectiveness of Drug Targeting Using PK and PK/PD Modelling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359 13.5.1 Effectiveness of an Ideal Carrier . . . . . . . . . . . . . . . . . . . . . 359 13.5.2 Implications of the DTI Concept . . . . . . . . . . . . . . . . . . . . 361 13.5.3 Drug Candidates for Effective Targeting . . . . . . . . . . . . . . . . 363 13.5.4 Limitations of PK and PK/PD Modelling . . . . . . . . . . . . . . . . 363 13.6 Examples of PK Modelling in Drug Targeting . . . . . . . . . . . . . . . . . . 364 13.6.1 In Vivo Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 13.6.2 In Vitro Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365 13.6.3 Regional Drug Administration . . . . . . . . . . . . . . . . . . . . . . 365 13.6.4 Controlled Drug Delivery . . . . . . . . . . . . . . . . . . . . . . . . 366 13.6.5 Pharmacokinetic Properties of Macromolecular Carrier Systems . . 366 13.7 Software for PK and PK/PD Modelling . . . . . . . . . . . . . . . . . . . . . 366 13.8 Perspectives and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . 367 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368 14 Drug Targeting Strategy: Scrutinize the Concepts Before Screening the Constructs Dirk K. F. Meijer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371 14.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371 14.2 Receptor-based drug targeting . . . . . . . . . . . . . . . . . . . . . . . . . . 372 14.3 Concluding remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
Drug Targeting Organ-Specific Strategies. Edited by G. Molema, D. K. F. Meijer Copyright © 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic) Abbreviations and Acronyms Aco aconitylated (Chapter 4); aconitic acid (Chapter 11) cis-Aco cis-aconitic acid ACE angiotensin-converting enzyme AD Alzheimer’s disease ADCC antibody dependent cellular cytotoxicity ADEPT antibody-directed enzyme pro-drug therapy ADP adenosine diphosphate AEA polyvinylacetal diethylaminoacetate AIA antigen-induced arthritis ALL acute lymphoblastic leukaemia AML acute myeloid leukaemia ALT alanine transaminase AMP adenosine monophosphate ANP atrial natriuretic peptide AOX alcohol oxidase (promoter) AP alkaline phosphatase AP-1 activator protein-1 APL acylated poly lysine APP amyloid precursor protein APC antigen presenting cell APS aerodynamic particle sizer AS-ODN antisense oligodeoxynucleotide AST aspartate transaminase ATP adenosine triphosphate AUC area under the (plasma concentration-time) curve AVP arginine vasopressin AZTMP azidothymidine-monophosphate BBB blood-brain barrier B-CSF-B blood-cerebrospinal fluid barrier BDL bile duct ligation BDNF brain derived neurotrophic factor BDO bile duct occlusion BMEC bovine microvessel endothelial cell BSA bovine serum albumin
Page 1 and 2: Drug Targeting Organ-Specific Strat
Page 3 and 4: Drug Targeting Organ-Specific Strat
Page 5 and 6: Preface Drug Targeting Organ-Specif
Page 7 and 8: Foreword Drug Targeting Organ-Speci
Page 9 and 10: X List of Contributors Henderik W.
Page 11 and 12: XII List of Contributors Grietje Mo
Page 13 and 14: Contents Drug Targeting Organ-Speci
Page 15 and 16: Contents XVII 3 Pulmonary Drug Deli
Page 17 and 18: Contents XIX 5.2.1.6 Identification
Page 19 and 20: Contents XXI 7.5 In Vitro Technique
Page 21 and 22: Contents XXIII 9.4 Tumour Vasculatu
Page 23: Contents XXV 12.8. Tissue Slices fr
Page 27 and 28: Dexa dexamethasone DIVEMA divinyl e
Page 29 and 30: LRP lung resistance related protein
Page 31 and 32: ROS reactive oxygen species RSV res
Page 33 and 34: Index a ADEPT 217, 224, 268, 291 ad
Page 35 and 36: e E. coli expression system 292 eff
Page 37 and 38: polymers, soluble 4, 218 - dendrime
Page 39 and 40: 2 1 Drug Targeting: Basic Concepts
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38 2 Brain-Specific Drug Targeting
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54 3 Pulmonary Drug Delivery: Deliv
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4 Cell Specific Delivery of Anti-In
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The sinusoids are lined by the disc
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4.2.2.2 Phagocytosis and Transcytos
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ther inflammatory cells or accessor
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4.3 Hepatic Inflammation and Fibros
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process is not yet available. Sever
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this carrier to the KCs.When the ma
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e taken up rapidly by mannose recep
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y the transcriptional regulatory pr
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4.8 Testing Liver Targeting Prepara
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4.8 Testing Liver Targeting Prepara
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4.9 Targeting of Anti-inflammatory
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4.9 Targeting of Anti-inflammatory
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with monoclonal and bispecific anti
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References 117 [50] Coleman DL, Eur
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References 119 [133] Cronstein BN,
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5 Delivery of Drugs and Antisense O
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5.1 Introduction 123 convoluted tub
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treatment of the targeted cell and
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CL uptake (ml/min/g) centration pro
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5.2.1.4 Specific Binding of Alkylgl
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5.2 Renal Delivery Using Pro-Drugs
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5.2 Renal Delivery Using Pro-Drugs
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5.3 Renal Delivery Using Macromolec
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5.4 Renal Delivary of Antisense Oli
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5.4 Renal Delivery of Antisense Oli
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5.4.8 Benefits and Limitations of A
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via reabsorption from the luminal s
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References 153 [66] Franssen EJF, M
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References 155 [145] Van Zwieten PA
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158 6 A Practical Approach in the D
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172 7 Vascular Endothelium in Infla
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8 Strategies for Specific Drug Targ
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8.2.2 Histogenesis The traditional
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may become obstructed and compresse
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8.5 Strategies to Deliver Drugs to
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8.5 Strategies to Deliver Drugs to
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larly cytotoxic immune effector cel
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contributes to limited tumour penet
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ples onto anti-EGP-2 scFv. Biologic
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In the case of drug-monoclonal anti
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cells, the presence of co-stimulato
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Monomethoxy-polyethylene glycol CH
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e efficiently loaded into the lipos
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8.6 Clinical Studies 223 Table 8.5.
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8.6.3 (Synthetic) (co)Polymers Solu
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8.8 Conclusions and Future Perspect
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References 229 [43] Chaouchi NA, Va
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References 231 [126] Czuczman MS, G
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234 9 Tumour Vasculature Targeting
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256 10 Phage Display Technology for
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11 Development of Proteinaceous Dru
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carrier is an homogenous product. I
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11.3 The Homing Device 11.3 The Hom
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malian cell lines that have acquire
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jugates for the delivery of other a
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11.5 The Linkage Between Drug and C
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actions are directed towards these
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11.5 The Linkage Between Drug and C
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homing potential if the antigen rec
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ly used promoters include T7 RNA po
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the baculovirus expression vector,
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11.8 Recombinant DNA Constructs 297
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11.8 Recombinant DNA Constructs 299
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toxic activity. Anthrax and tetanus
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11.9 Recombinant Domains as Buildin
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References 305 [16] Milstein C, Wal
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References 307 [99] Verma R, Boleti
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12 Use of Human Tissue Slices in Dr
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are also extensively used in a vari
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Meanwhile many incubation systems h
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12.3 Incubation and Culture of Live
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to investigate the effect of differ
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The mechanisms of uptake and excret
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12.6 The Use of Liver Slices in Dru
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12.7 Efficacy Testing of the Drug T
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NO x µM 80 60 40 20 * * 12.7 Effic
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TNFα ng/ml 1.5 1 0.5 0 * Human (n=
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References 329 [33] Ikejima K, Enom
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References 331 [109] Dutt A, Priebe
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334 13 Pharmacokinetic/Pharmacodyna
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372 14 Drug Targeting Strategy: Scr
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374 14 Drug Targeting Strategy: Scr
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Drug Targeting Organ-Specific Strategies

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