Drug Targeting Organ-Specific Strategies

More documents

Recommendations

Info

XVIII Contents 4.3 Hepatic Inflammation and Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . 96 4.4 Liver Cirrhosis: Causes and Therapy . . . . . . . . . . . . . . . . . . . . . . . 98 4.5 Drug Targeting to the Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 4.5.1 Carriers Directed at SECs and KCs . . . . . . . . . . . . . . . . . . . 100 4.5.1.1 Albumins . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 4.5.1.2 Liposomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 4.5.1.3 Carriers with Intrinsic Anti-inflammatory Activity . . . . . 102 4.5.2 Targeting to other Hepatic Cells . . . . . . . . . . . . . . . . . . . . . 103 4.6 Anti-inflammatory Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 4.6.1 Nonsteroidal Anti-inflammatory Drugs (NSAIDs) . . . . . . . . . . 103 4.6.2 Glucocorticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 4.6.3 Other Anti-inflammatory Drugs . . . . . . . . . . . . . . . . . . . . . 105 4.7 Anti-fibrotic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 4.8 Testing Liver Targeting Preparations . . . . . . . . . . . . . . . . . . . . . . . 106 4.8.1 Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 4.8.2 Cellular Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 4.8.3 Efficacy and Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 4.9 Targeting of Anti-inflammatory Drugs for the Treatment of Liver Fibrosis . . 110 4.9.1 Targeting of NSAIDs . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 4.9.2 Targeting of Glucocorticosteroids . . . . . . . . . . . . . . . . . . . . 112 4.10 Selective Drug Delivery for the Treatment of Other Hepatic Disorders . . . 114 4.11 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 5 Delivery of Drugs and Antisense Oligonucleotides to the Proximal Tubular Cell of the Kidney Using Macromolecular and Pro-drug Approaches Marijke Haas, Yukio Kato, R. Folgert G. Haverdings, Frits Moolenaar, Kokichi Suzuki, Dick de Zeeuw, Yuichi Sugiyama, Dirk K. F. Meijer . . . . . . 121 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 5.1.1 Kidneys and their Functions . . . . . . . . . . . . . . . . . . . . . . . 121 5.1.2 Proximal Tubular Cells and their Functions . . . . . . . . . . . . . . . 123 5.1.3 Cellular Targets for Drug Delivery in the Kidney . . . . . . . . . . . 124 5.1.4 Renal Pathology and the Proximal Tubular Cell for Therapeutic Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 5.1.5 Targeting to the Proximal Tubular Cell . . . . . . . . . . . . . . . . . 125 5.2 Renal Delivery Using Pro-Drugs . . . . . . . . . . . . . . . . . . . . . . . . . 126 5.2.1 The Alkylglycoside Approach . . . . . . . . . . . . . . . . . . . . . . 126 5.2.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 5.2.1.2 Concept of the Alkylglycoside Approach . . . . . . . . . . 126 5.2.1.3 Distribution of Alkylglycoside-derivatized AVP In Vivo . . 126 5.2.1.4 Specific Binding of Alkylglycoside-derivatized AVP in Kidney Plasma Membranes . . . . . . . . . . . . . . . . . 129 5.2.1.5 Structure–Kinetic Relationship Studies . . . . . . . . . . . 129
Contents XIX 5.2.1.6 Identification of Target Molecules for Alkylglycosides . . . 131 5.2.1.7 Perspectives of Renal Delivery with Alkylglycoside Vectors 131 5.2.2 The Amino Acid Pro-drug Approach . . . . . . . . . . . . . . . . . . 132 5.2.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 5.2.2.2 The Concept of the Amino Acid Pro-drug . . . . . . . . . . 132 5.2.2.3 Renal Specificity of Amino Acid Pro-drug and their Effects 133 5.2.2.4 Benefits and Limitations of the Amino Acid Pro-drug . . . 133 5.2.2.5 The Soft Drug Concept . . . . . . . . . . . . . . . . . . . . 134 5.2.3 The Folate Pro-drug Approach . . . . . . . . . . . . . . . . . . . . . . 134 5.2.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 5.2.3.2 Potential Renal Selectivity of Folate Constructs . . . . . . . 134 5.2.3.3 Benefits and Limitations of Folate . . . . . . . . . . . . . . 135 5.3 Renal Delivery Using Macromolecular Carriers: The Low-Molecular Weight Protein Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 5.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 5.3.2 Renal uptake of LMWP Conjugates . . . . . . . . . . . . . . . . . . . 137 5.3.2.1 Renal Uptake of Native LMWPs . . . . . . . . . . . . . . . 137 5.3.2.2 Renal Delivery of Naproxen–Lysozyme . . . . . . . . . . . 137 5.3.2.3 Renal Delivery of Captopril–Lysozyme . . . . . . . . . . . 138 5.3.3 Renal Catabolism of LMWP-conjugates . . . . . . . . . . . . . . . . 139 5.3.3.1 Renal Catabolism of Native LMWPs . . . . . . . . . . . . . 139 5.3.3.2 Renal Catabolism of Naproxen–Lysozyme . . . . . . . . . 141 5.3.3.3 Renal Catabolism of Captopril–Lysozyme . . . . . . . . . . 141 5.3.4 Effects of Targeted Drugs Using an LMWP as Carrier . . . . . . . . 141 5.3.4.1 Renal Effects of Naproxen–Lysozyme . . . . . . . . . . . . 141 5.3.4.2 Renal and Systemic Effects of Captopril–Lysozyme . . . . 142 5.3.5 Renal Disease and LMWP Processing . . . . . . . . . . . . . . . . . 142 5.3.6 Renal Delivery of High Doses of LMWPs . . . . . . . . . . . . . . . 143 5.3.7 Limitations of the LMWP Strategy of Drug Delivery to the Kidney . 144 5.4 Renal Delivery of Antisense Oligodeoxynucleotides . . . . . . . . . . . . . . 144 5.4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 5.4.2 Mechanism of Action of Antisense Oligodeoxynucleotides . . . . . . 145 5.4.3 Stabilization of Antisense Oligodeoxynucleotides . . . . . . . . . . . 145 5.4.4 Pharmacokinetic Aspects of Antisense Oligodeoxynucleotides and Renal Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 5.4.5 Cellular Uptake of Antisense Oligodeoxynucleotides . . . . . . . . . 147 5.4.6 Metabolism and Elimination of Antisense Oligodeoxynucleotides . . 147 5.4.7 Effects of Antisense Targeting to the Proximal Tubule . . . . . . . . 148 5.4.8 Benefits and Limitations of Antisense Oligodeoxynucleotides . . . . 149 5.5 Drugs for Renal Targeting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 5.6 In Vitro and In Vivo Models for Renal Targeting . . . . . . . . . . . . . . . . 149 5.6.1 In Vitro Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 5.6.2 In Vivo Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 5.7 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Page 1 and 2: 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: Contents XVII 3 Pulmonary Drug Deli
Page 19 and 20: Contents XXI 7.5 In Vitro Technique
Page 21 and 22: Contents XXIII 9.4 Tumour Vasculatu
Page 23 and 24: 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
Page 61 and 62: 24 2 Brain-Specific Drug Targeting
Page 67 and 68:
30 2 Brain-Specific Drug Targeting
Page 69 and 70:
Page 71 and 72:
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
Page 81 and 82:
Page 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
54 3 Pulmonary Drug Delivery: Deliv
Page 93 and 94:
Page 95 and 96:
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
Page 121 and 122:
Page 123 and 124:
Page 125 and 126:
4 Cell Specific Delivery of Anti-In
Page 127 and 128:
The sinusoids are lined by the disc
Page 129 and 130:
4.2.2.2 Phagocytosis and Transcytos
Page 131 and 132:
ther inflammatory cells or accessor
Page 133 and 134:
4.3 Hepatic Inflammation and Fibros
Page 135 and 136:
process is not yet available. Sever
Page 137 and 138:
this carrier to the KCs.When the ma
Page 139 and 140:
e taken up rapidly by mannose recep
Page 141 and 142:
y the transcriptional regulatory pr
Page 143 and 144:
4.8 Testing Liver Targeting Prepara
Page 145 and 146:
4.8 Testing Liver Targeting Prepara
Page 147 and 148:
4.9 Targeting of Anti-inflammatory
Page 149 and 150:
4.9 Targeting of Anti-inflammatory
Page 151 and 152:
with monoclonal and bispecific anti
Page 153 and 154:
References 117 [50] Coleman DL, Eur
Page 155 and 156:
References 119 [133] Cronstein BN,
Page 157 and 158:
5 Delivery of Drugs and Antisense O
Page 159 and 160:
5.1 Introduction 123 convoluted tub
Page 161 and 162:
treatment of the targeted cell and
Page 163 and 164:
CL uptake (ml/min/g) centration pro
Page 165 and 166:
5.2.1.4 Specific Binding of Alkylgl
Page 167 and 168:
5.2 Renal Delivery Using Pro-Drugs
Page 169 and 170:
5.2 Renal Delivery Using Pro-Drugs
Page 171 and 172:
5.3 Renal Delivery Using Macromolec
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
5.4 Renal Delivary of Antisense Oli
Page 183 and 184:
5.4 Renal Delivery of Antisense Oli
Page 185 and 186:
5.4.8 Benefits and Limitations of A
Page 187 and 188:
via reabsorption from the luminal s
Page 189 and 190:
References 153 [66] Franssen EJF, M
Page 191 and 192:
References 155 [145] Van Zwieten PA
Page 193 and 194:
158 6 A Practical Approach in the D
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Page 205 and 206:
Page 207 and 208:
172 7 Vascular Endothelium in Infla
Page 209 and 210:
Page 211 and 212:
Page 213 and 214:
Page 215 and 216:
Page 217 and 218:
Page 219 and 220:
Page 221 and 222:
Page 223 and 224:
Page 225 and 226:
Page 227 and 228:
Page 229 and 230:
Page 231 and 232:
Page 233 and 234:
8 Strategies for Specific Drug Targ
Page 235 and 236:
8.2.2 Histogenesis The traditional
Page 237 and 238:
may become obstructed and compresse
Page 239 and 240:
8.5 Strategies to Deliver Drugs to
Page 241 and 242:
8.5 Strategies to Deliver Drugs to
Page 243 and 244:
larly cytotoxic immune effector cel
Page 245 and 246:
contributes to limited tumour penet
Page 247 and 248:
ples onto anti-EGP-2 scFv. Biologic
Page 249 and 250:
In the case of drug-monoclonal anti
Page 251 and 252:
cells, the presence of co-stimulato
Page 253 and 254:
Monomethoxy-polyethylene glycol CH
Page 255 and 256:
e efficiently loaded into the lipos
Page 257 and 258:
8.6 Clinical Studies 223 Table 8.5.
Page 259 and 260:
8.6.3 (Synthetic) (co)Polymers Solu
Page 261 and 262:
8.8 Conclusions and Future Perspect
Page 263 and 264:
References 229 [43] Chaouchi NA, Va
Page 265 and 266:
References 231 [126] Czuczman MS, G
Page 267 and 268:
234 9 Tumour Vasculature Targeting
Page 269 and 270:
Page 271 and 272:
Page 273 and 274:
Page 275 and 276:
Page 277 and 278:
Page 279 and 280:
Page 281 and 282:
Page 283 and 284:
Page 285 and 286:
Page 287 and 288:
Page 289 and 290:
256 10 Phage Display Technology for
Page 291 and 292:
Page 293 and 294:
Page 295 and 296:
Page 297 and 298:
Page 299 and 300:
Page 301 and 302:
Page 303 and 304:
Page 305 and 306:
Page 307 and 308:
11 Development of Proteinaceous Dru
Page 309 and 310:
carrier is an homogenous product. I
Page 311 and 312:
11.3 The Homing Device 11.3 The Hom
Page 313 and 314:
malian cell lines that have acquire
Page 315 and 316:
jugates for the delivery of other a
Page 317 and 318:
11.5 The Linkage Between Drug and C
Page 319 and 320:
actions are directed towards these
Page 321 and 322:
11.5 The Linkage Between Drug and C
Page 323 and 324:
homing potential if the antigen rec
Page 325 and 326:
ly used promoters include T7 RNA po
Page 327 and 328:
the baculovirus expression vector,
Page 329 and 330:
11.8 Recombinant DNA Constructs 297
Page 331 and 332:
11.8 Recombinant DNA Constructs 299
Page 333 and 334:
toxic activity. Anthrax and tetanus
Page 335 and 336:
11.9 Recombinant Domains as Buildin
Page 337 and 338:
References 305 [16] Milstein C, Wal
Page 339 and 340:
References 307 [99] Verma R, Boleti
Page 341 and 342:
12 Use of Human Tissue Slices in Dr
Page 343 and 344:
are also extensively used in a vari
Page 345 and 346:
Meanwhile many incubation systems h
Page 347 and 348:
12.3 Incubation and Culture of Live
Page 349 and 350:
to investigate the effect of differ
Page 351 and 352:
The mechanisms of uptake and excret
Page 353 and 354:
12.6 The Use of Liver Slices in Dru
Page 355 and 356:
12.7 Efficacy Testing of the Drug T
Page 357 and 358:
NO x µM 80 60 40 20 * * 12.7 Effic
Page 359 and 360:
TNFα ng/ml 1.5 1 0.5 0 * Human (n=
Page 361 and 362:
References 329 [33] Ikejima K, Enom
Page 363 and 364:
References 331 [109] Dutt A, Priebe
Page 365 and 366:
334 13 Pharmacokinetic/Pharmacodyna
Page 367 and 368:
Page 369 and 370:
Page 371 and 372:
Page 373 and 374:
Page 375 and 376:
Page 377 and 378:
Page 379 and 380:
Page 381 and 382:
Page 383 and 384:
Page 385 and 386:
Page 387 and 388:
Page 389 and 390:
Page 391 and 392:
Page 393 and 394:
Page 395 and 396:
Page 397 and 398:
Page 399 and 400:
Page 401 and 402:
Page 403 and 404:
372 14 Drug Targeting Strategy: Scr
Page 405 and 406:
374 14 Drug Targeting Strategy: Scr
show all

Drug Targeting Organ-Specific Strategies

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?