Advances in Drug Delivery Systems, 6 (eBook)

Proceedings of the Sixth International Symposium on Recent Advances in Drug Delivery Systems, Salt Lake City, UT, U.S.A., February 21-24, 1993

James M. Anderson, Sung Wan Kim, Jindrich Kopecek (Herausgeber)

eBook Download: PDF

2013 | 1. Auflage
372 Seiten
Elsevier Science (Verlag)
978-1-4831-6157-0 (ISBN)

Infos

Advances in Drug Delivery Systems, 6 focuses on the progress in drug delivery systems as manifested in the fields of international pharmaceutics, polymer science, biotechnology, molecular biology, and cell biology. The selection first tackles biologically engineered microstructures and approaches to targeting bioactive compounds. Discussions focus on therapeutic efficiency of fatty acylated antiviral antibodies; effect of artificial fatty acylation on protein binding and uptake; and controlled release of proteins from lipid microcylinders. The text then elaborates on mucosal delivery of macromolecules and targeted delivery of diagnostic agents by surface-modified liposomes. The book examines the factors on in vitro micelle stability of adriamycin-block copolymer conjugates; vaginal and reproductive system treatments using a bioadhesive polymer; and control of the disposition profiles of proteins in the kidney via chemical modification. The publication also takes a look at drug delivery using biodegradable microspheres; approaches to improved antibody- and peptide-mediated targeting for imaging and therapy of cancer; and biodegradable microspheres for the delivery of oral vaccines. The selection is a valuable source material for scientists and readers interested in the advances in the systems of drug delivery.

Inhalt

Front Cover 1
Advances in Drug Delivery Systems, 6 4
Copyright Page 5
Table of Contents 10
Preface 6
Part I: Novel Drug Delivery Systems 14
Chapter 1. Biologically engineered microstructures: controlled release applications 16
Introduction 16
Microstructure geometry and controlled release 17
Flat porus media 17
Spheres 18
Rigid hollow microcylinders 20
Controlled release from microcylinders 21
Antifouling applications 21
Methods for environmental exposure testing 22
Controlled release of proteins from lipid microcylinders 23
Summary and Conclusion 25
Acknowledgements 25
References 25
Chapter 2. New approaches to targeting bioactive compounds 28
Introduction 28
Fatty acylated antibodies 29
Effect of artificial fatty acylation on protein binding and uptake 29
Suppression of virus reproduction with fatty acylated antiviral antibodies 31
Therapeutic efficiency of fatty acylated antiviral antibodies 34
Antisense oligonucleotides combined with a lipid moiety 35
DNA interpolyelectrolyte complexes as a tool for gene delivery into a cell 37
Respecrins: a new class of immunotoxins 41
Acknowledgments 44
References 44
Chapter 3. Mucosal delivery of macromolecules 50
Introduction 50
Experimental 51
Materials 51
Buccal solution preparation 51
Buccal device fabrication 51
In vivo experiments 52
Intravenous bolus experiments 52
Buccal solution experiments 52
Buccal device experiments 52
Results and Discussion 53
Conclusions 57
References 57
Chapter 4. Targeted delivery of diagnostic agents by surface-modified liposomes 58
Introduction 59
The mechanism of protective action of PEG on liposomes 61
Co-immobilization of PEG and antibody on the liposome surface: long-circulating immunoliposome accumulation in myocardial infarct 63
Surface modification of liposomes with chelating groups for delivery of imaging agents: lymph node visualization and modification of MRI contrast properties of Gd-liposomes 66
Acknowledgement 70
References 70
Chapter 5. Influencing factors on in vitro micelle stability of adriamycin-block copolymer conjugates 72
Introduction 72
Experimental part 73
Materials 73
Preparation of drug-block copolymer conjugates 73
HPLC measurements 74
Results and Discussion 75
Conclusions 77
Acknowledgements 77
References 77
Chapter 6. SK& F 110679: comparison of absorption following oral or respiratory administration
Introduction 81
Materials and Methods 81
Chemicals 81
Intestinal transport of SK& F 110679
Intraduodenal administration of SK& F 110679
Intratracheal dosing and measurement of plasma growth hormone levels in rats 83
Intratracheal and intravenous dosing of SK& F 110679 in dogs
Measurement of plasma levels of SK& F 110679
Data analysis 84
Transport of [3H]SK& F 110679 across rabbit intestinal mucosa in vitro
Absorption of SK& F 110679 in the rat
Plasma concentrations of SK& F 110679 following intravenous, intraduodenal or intratracheal administration in dogs
Discussion 87
Acknowledgements 88
References 88
Chapter 7. Bioavailability of pulmonary delivered peptides and proteins: a-interferon, calcitonins and parathyroid hormones 92
Introduction 92
Experimental 93
Materials 93
Animal studies 93
Assays 94
Results 94
Discussion and Summary 95
References 97
Chapter 8. Vaginal and reproductive system treatments using a bioadhesive polymer 100
Introduction 100
Relevant anatomy and physiology 100
Bioadhesion 101
Dosage form properties 101
Clinical applications 102
References 107
Part II: Peptide and Protein Delivery 108
Chapter 9. Paracellular transport of a proteolytically labile pentapeptide across the colonic and other intestinal segments of the albino rabbit: implications for peptide drug design 110
Introduction 111
Materials and Methods 111
Materials 111
Methods 111
Results 114
Acknowledgements 121
References 121
Chapter 10. Control of the disposition profiles of proteins in the kidney via chemical modification 124
Introduction 124
Materials and methods 125
Model protein drugs and macromolecules 125
Synthesis of SOD derivatives 125
Kidney perfusion experiments 125
Indicator dilution experiments 126
Assay 126
Data analysis 126
Results and discussion 127
Disposition characteristics of model protein drugs and macromolecules 127
Disposition characteristics of SOD derivatives 129
Implications for therapeutic use of SOD derivatives in the renal injuries 130
Conclusions 130
References 131
Chapter 11. Drug delivery using biodegradable microspheres 134
Introduction 134
Experimental methods 135
Materials and animals 135
Ovulation-inducing activity 135
Preparation of microspheres 135
In vitro drug release 135
Leuprorelin content in microspheres 136
TRH content in microspheres 136
In vivo drug release 136
RIA of serum leuprorelin and testosterone 136
Anticancer effects of TNP-470 microspheres 136
Results and discussion 136
Leuprorelin microspheres 136
TRH Microspheres 139
Chemoembolization with microspheres containing TNP-470 140
References 141
Chapter 12. Biodegradable microspheres for the delivery of oral vaccines 144
Introduction 144
Mucosal immune responses and the common mucosal immune system 145
Antigen delivery systems for mucosal vaccines 146
Biodegradable microspheres 146
Mucosal immunity to influenza 148
Immunogenicity of the microencapsulated influenza virus 148
Systemic and oral immunization with microencapsulated or free influenza virus 149
Potential advantages of mucosal immunization with antigens in biodegradable microspheres 152
References 152
Chapter 13. pH/Temperature-sensitive polymers for macromolecular drug loading and release 156
Introduction 156
Experimental methods 157
Materials 157
Polymer synthesis 158
Molecular weight and lower critical solution temperature (LCST) determination 158
Polymer beads fabrication 158
Scanning electron microscopy (SEM) 158
Solute loading and loading efficiency 158
Results and Discussion 159
Conclusion 164
Acknowledgment 164
References 164
Part III: Targetting and Cellular Recognition in Drug Delivery 166
Chapter 14. Antibodies as targeting moieties: affinity measurements, conjugation chemistry and applications in immunoliposomes 168
Introduction 168
Experimental methods 170
Monoclonal antibodies 170
Preparation of antigen-binding fragments 170
Design and synthesis of antigen-mimicking peptides 170
Preparation of labelled peptides 170
Fluorescence polarization measurement 170
Affinity measurements for 4-4-20 171
Preparation of liposomes 171
Coupling of antigen-binding fragments to liposomes 171
Production of RES-avoiding immunoliposomes 171
Results and discussion 171
Affinity measurements 171
RES-avoiding immunoliposomes 174
Conclusions 177
Acknowledgements 177
References 177
Chapter 15. Approaches to improved antibody- and peptide-mediated targeting for imaging and therapy of cancer 180
Introduction 180
Materials and Methods 181
Monoclonal antibodies and other carriers 181
Blood disappearance half life measurement 181
LS-180 xenograft nude mouse model 181
Results 182
Discussion 183
Bone marrow support 184
Pretargeting approach 184
Tumor targeting peptides 184
Summary 185
Acknowledgements 185
References 185
Chapter 16. Bacterial cell killing by antibody targeted photolysis: enhanced effect by OH radical generation 188
Introduction 188
Materials and methods 190
Reagents and solutions 190
Preparation of Sn-chlorin e6-DC and Sn-chlorin e6-DC immunoconjugates 190
Preparation of Sn-chlorin e6-ED immunoconjugates 191
Spin trapping with DMPO 191
Free radical quantum yields 191
Singlet oxygen yields 192
O2 uptake measurements 192
Bacterial survival protocol 193
Results 193
Comparison of the killing efficiency of two immunoconjugates 193
Spin trapping OH 194
Quantitative radical quantum yields 195
Rate of 02 uptake by PS and DC co-solution 196
Discussion 197
References 198
Chapter 17. Antibody-directed enzyme prodrug therapy (Adept) 200
Introduction 200
Pharmacokinetics of antibody-enzyme conjugate 201
Presence of cytotoxic drug in blood 203
Host immune response 204
Acknowledgements 206
References 206
Chapter 18. Targeting the vasculature of solid tumors 208
Introduction 208
Methods 209
Mouse vascular targeting model 209
Preparation of deglycosylated ricin A chain 209
Cytotoxicity assays 209
Antitumor experiments 210
Results 210
Discussion 214
Acknowledgements 215
References 215
Chapter 19. Synthesis of the conjugate of Superoxide dismutase with the copolymer of divinyl ether and maleic anhydride retaining enzymatic activity 216
Introduction 216
Material and Methods 217
Synthesis of DIVEMA-SOD conjugate 218
Characterization of DIVEMA-SOD 218
Results and Discussion 218
References 221
Chapter 20. Bioadhesive N-(2-hydroxypropyl) methacrylamide copolymers for colon-specific drug delivery 224
Introduction 224
Materials and Methods 225
Abbreviations 225
Chemicals 225
Synthesis of 5-aminosalicylic acid-containing monomer 225
Synthesis of N-(2-hydroxypropyl) methacrylamide copolymers 226
Radioiodination of polymers 227
Biological samples for azoreductase activity measurements 228
Degradation by cecum contents/feces 228
Bioadhesion of polymers in vitro 228
Gastrointestinal distribution of polymers in vivo 228
Results and Discussion 229
Synthesis 229
Degradation by colonic azoreductase activity 230
Comparison of azoreductase activity in different species 231
Bioadhesion of HPMA copolymers to everted intestinal sacs 232
Bioadhesion of HPMA copolymers in vivo 233
Acknowledgement 234
References 234
Chapter 21. Lactose-carrying polystyrene as a drug carrier: investigation of body distributions to parenchymal liver cells using 125I-labelled lactose-carrying polystyrene 236
Experimental 238
Polymer synthesis 238
Preparation of 125I-labelled PVLA solution 238
Assay of radioactivity 238
Animals 238
Body distribution of 125I-labelled PVLA in rats 239
Whole-body autoradiography of 125I-PVLA administered rat 239
Distribution of 125I-labelled PVLA between parenchymal and nonparenchymal liver cells 239
Clearance of 125I-labelled PVLA from blood and its pharmacokinetic analysis 239
Binding of 125I-PVLA to asialoglycoprotein receptors and its Scatchard analysis 239
Results and Discussion 240
Body distribution of 125I-labelled PVLA 240
Pharmacokinetic analysis of 125I-labelled PVLA 242
Binding of 125I-PVLA to asialoglycoprotein receptors and its Scatchard analysis 243
References 245
Chapter 22. Induction of drug specific antibody and the controlled release of drug by 6-O-carboxymethyl-chitin 248
Introduction 248
Experimental 249
Results and Discussion 250
Conclusions 254
Acknowledgements 254
References 254
Chapter 23. Recent clinical studies on lipo-PGEi and lipo-PGI2: PGE1 and PGI2: incorporated in lipid microspheres, for targeted delivery 256
Introduction 256
Methods and Results 257
Diabetic neuropathy and diabetic ulcers 257
Fulminant or severe acute hepatitis 258
Acute cerebral thrombosis 259
Discussion 260
Acknowledgements 261
References 261
Part IV: Drug Delivery to the Brain 264
Chapter 24. Encapsulated cells for sustained neurotransmitter delivery to the central nervous system 266
Introduction 266
Treatment of Parkinson's disease 267
Alleviation of pain 269
Concluding remarks 270
Acknowledgements 270
References 270
Chapter 25. Drug transport to the brain: in vitro versus in vivo approaches 272
Introduction 272
Materials and Methods 272
Results 273
The in vitro BBB model 273
Confocal laser scanning microscopy 274
The in vivo BBB model 274
Intracerebral microdialysis 274
Discussion 274
Conclusion 275
References 275
Part V: Posters: Transmembrane Transport 278
Chapter 26. BUCCAL ADMINISTRATION OF ERYTHROCYTE-GHOSTS-INSULIN IN RATS 280
INTRODUCTION 280
EXPERIMENTAL METHODS 280
CONCLUSION 281
REFERENCES 281
ACKNOWLEDGEMENTS 281
Chapter 27. In-Vivo Buccal Delivery of Calcitonin 282
Introduction 282
Experimental 282
Results and Discussion 283
Conclusion 284
References 284
Chapter 28. INVESTIGATING THE BIOADHESIVE PROPERTIES OF POLYMER PATCHES FOR BUCCAL DRUG DELIVERY 285
INTRODUCTION 285
EXPERIMENTAL METHODS 285
RESULTS AND DISCUSSION 285
CONCLUSIONS 286
REFERENCES 286
Chapter 29. DIFFUSION RATES AND TRANSPORT PATHWAYS OF FITC-LABELLED MODEL COMPOUNDS THROUGH BUCCAL EPITHELIUM. 287
Chapter 30. ENHANCING EFFECTS OF VARIOUS STRUCTURES OF UNSATURATED FATTY ACIDS ON THE PERCUTANEOUS PERMEATION OF INDOMETHACIN 288
INTRODUCTION 288
METHODS 288
RESULTS and DISCUSSION 289
REFERENCES 289
Chapter 31. SELECTIVE EXTRACTION OF STRATUM CORNEUM COMPONENTS TO PROBE MECHANISMS OF ENHANCED PERCUTANEOUS ABSORPTION 290
INTRODUCTION 290
EXPERIMENTAL METHODS 290
RESULTS AND DISCUSSION 291
CONCLUSIONS 291
REFERENCES 291
ACKNOWLEDGEMENTS 291
Chapter 32. STUDY ON TRANSDERMAL SODIUM NITROPRUSSIDE DELIVERY SYSTEM 292
INTRODUCTION 292
EXPERMENTAL METHODS 292
RESULTS AND DISCUSSION 293
REFERENCE 294
Chapter 33. WATER SOLUBLE PILOCARPINE PRODRUGS WITH SUSTAINED INTRAOCULAR ACTIVITY IN NORMOTENSIVE RABBITS AND IN GLAUCOMATOUS BEAGLES 295
INTRODUCTION 295
EXPERIMENTAL 295
RESULTS AND DISCUSSION 296
CONCLUSION 296
Chapter 34. TRANSPORT OF SMALL PEPTIDES ACROSS RAT ALVEOLAR EPITHELIAL CELL MONOLAYERS 297
INTRODUCTION 297
METHODS 297
RESULTS AND DISCUSSION 298
REFERENCES 298
ACKNOWLEDGEMENTS: 298
Chapter 35. RECEPTOR-MEDIATED ABSORPTION OF DEXTRAN AND SYNTHETIC GLUCOSE—CONTAINING POLYMER FROM THE INTESTINAL TRACT 299
INTRODUCTION 299
EXPERIMENTAL METHODS 299
RESULTS AND DISCUSSION 299
Chapter 36. EFFECT OF POLYCARBOPHIL ON THE PARACELLULAR PERMEABILITY OF A HYDROPHILIC MODEL COMPOUND AFTER APPLICATION ON A CACO-2 CELL LINE 301
Chapter 37. USE OF A LIPID CARRIER TO DELIVER CALCITONIN VIA THE SMALL INTESTINE 302
INTRODUCTION 302
METHODS 302
RESULTS 303
CONCLUSION 303
Chapter 38. INTRAVENOUS CARRIERS FOR DRUG DELIVERY TO LYMPH NODES 306
EXPERIMENTAL METHODS 306
RESULTS AND DISCUSSION 307
CONCLUSION 307
Chapter 39. TARGETED CONJUGATE BETWEEN ANTIMYOSIN AND RADIOLABELED CHELATING POLYMER: INFLUENCE OF SINGLE SITE FAB-POLYMER BOND ON THE CONJUGATE PERFORMANCE. 308
INTRODUCTION. 308
MATERIALS AND METHODS. 308
RESULTS AND DISCUSSION. 308
REFERENCES. 309
Chapter 40. STEREOCOPOLYMERS FOR PARENTERAL SUSTAINED-RELEASE OF PEPTIDES: RELEASE OF GRF29NH2 FROM A PLA/GA MATRIX 310
INTRODUCTION 310
EXPERIMENTAL METHODS 310
RESULTS AND DISCUSSION 311
CONCLUSIONS 311
REFERENCES 311
Chapter 41. THE EFFECT OF CHARGE ON THE BIODISTRIBUTION OF SYNTHETIC BRANCHED POLYPEPTIDES IN TUMOUR BEARING MICE 314
INTRODUCTION 314
EXPERIMENTAL 314
RESULTS AND CONCLUSION 315
REFERENCE 315
Chapter 42. COMPARATIVE IN VIVO AND IN VITRO DISTRIBUTION OF DAUNOXOME AND DAUNORUBICIN IN P1798 LYMPHOSARCOMA CELLS 316
REFERENCES 317
Chapter 43. BIOPHARMACEUTICS AND PHARMACOKINETICS OF [D-ALA2, DLEU5] ENKEPHALIN AFTER VARIOUS ROUTES OF ADMINISTRATION 318
Chapter 44. Greatly enhanced oral bioavailability of propranolol using the 
319 
INTRODUCTION 319
EXPERIMENTAL METHODS 319
RESULTS 320
DISCUSSION 320
CONCLUSION 322
REFERENCES 322
Part VI: Novel Therapeutic Delivery Systems 324
Chapter 45. NOVEL, LONG-ACTING AND SELECTIVE PHYSOSTIGMINE ANALOGUES AS POTENTIAL THERAPEUTICS FOR ALZHEIMER'S DISEASE 326
Chapter 46. LECITHINIZED SUPEROXIDE DISMUTASE -AN EFFECTIVE DRUG DELIVERY SYSTEM 327
INTRODUCTION 327
EXPERIMENTAL METHOD 327
RESULTS AND DISCUSSION 327
CONCLUSION 328
Chapter 47. TWO DERIVATIVES OF POLY(ACRYLIC ACID) ARE ABLE TWO INHIBIT TRYPSIN ACTIVITY 329
Chapter 48. CONTROLLED RELEASE OF INSULIN FROM BORONIC ACID GEL UNDER PHYSIOLOGICAL CONDITIONS 330
INTRODUCTION 330
EXPERIMENTAL METHODS 330
RESULTS AND DISCUSSION 331
CONCLUSIONS 331
REFERENCES 331
Chapter 49. NOVEL THERMO-RESPONSIVE AMPHIPHILIC POLY N-ISOPROPYLACRYLAMIDE- CO-SODIUM ACRYIATE-CO-N-N-ALKYLACRYLAMIDE NETWORKS 332
INTRODUCTION 332
EXPERIMENTAL METHODS 332
RESULTS, DISCUSSION, CONCLUSIONS 332
REFERENCES 333
ACKNOWLEDGEMENTS 333
Chapter 50. DELIVERY OF CYTOTOXIC DRUGS TO CANCER PATIENTS USING LOW DENSITY LIPOPROTEIN 334
INTRODUCTION 334
STUDY DESIGN 334
RESULTS 335
DISCUSSION 335
REFERENCES 335
Chapter 51. DEVELOPMENT AND CLINICAL EVALUATION OF DOUBLE-PHASED SUPPOSITORIES OF PROGESTERONE WITH SUSTAINED RELEASE PROPERTY 336
INTRODUCTION 336
EXPERIMENTAL METHODS 336
RESULTS AND DISCUSSIONS 337
Chapter 52. MACROMOLECULAR COMPLEXONE FOR DETECTION OF MICROVASCULATURE BY MAGNETIC RESONANCE ANGIOGRAPHY 338
INTRODUCTION 338
EXPERIMENTAL METHODS 338
RESULTS AND DISCUSSION 339
CONCLUSION 339
REFERENCES 339
Chapter 53. CRIPDOM CONTROLLED DELIVERY SYSTEM FOR ASPIRIN 340
INTRODUCTION 340
EXPERIMENTAL METHODS 340
RESULTS AND DISCUSSION 340
CONCLUSIONS 341
REFERENCES 341
Chapter 54. Liposome and Microsphere Transport and Delivery 342
Chapter 55. EFFECT OF LIPID BILAYER PHASE STRUCTURE ON SOLUTE PARTITIONING 344
INTRODUCTION 344
EXPERIMENTAL METHODS 344
RESULTS AND DISCUSSION 345
CONCLUSIONS 345
REFERENCES 346
Chapter 56. ENHANCED TUMOR ACCUMULATION AND PROLONGED CIRCULATION TIMES OF MICELLE-FORMING POLYETHYLENE OXIDE-ASPARTATE) BLOCK COPOLYMER-ADRIAMYCIN CONJUGATES 347
INTRODUCTION 347
EXPERIMENTAL METHODS 347
RESULTS AND DISCUSSION 347
CONCLUSIONS 348
REFERENCES 348
Chapter 57. IN VIVO ANTITUMOR ACTIVITY OF POLYMERIC MICELLE ANTICANCER DRUG AGAINST MURINE C 26 TUMOR 349
INTRODUCTION 349
EXPERIMENTAL METHODS 349
RESULTS & DISCUSSION
CONCLUSIONS 350
REFERENCES 350
Chapter 58. METHOD FOR ASSESSING THE STABILITY OF PROTEINOID MICROSPHERES 351
INTRODUCTION 351
EXPERIMENTAL METHODS 351
RESULTS AND DISCUSSION 352
CONCLUSIONS 352
REFERENCES 352
Chapter 59. SCREENING CANDIDATE MICROSPHERE FORMULATIONS BY INCUBATING IN SIMULATED DIGESTIVE FLUIDS 353
INTRODUCTION 353
EXPERIMENTAL METHODS 353
RESULTS AND DISCUSSION 354
CONCLUSIONS 354
REFERENCES 354
Chapter 60. STABILITY AND MODE OF ACTION OF AMBISOME® (LIPOSOMAL AMPHOTERICIN B) 355
REFERENCES 356
Chapter 61. APPLICATION OF LIPID MICROSPHERES TO PREPARE A THROMBOXANE A2 RECEPTOR ANTAGONIST INHALER 357
INTRODUCTION 357
EXPERIMENTAL METHODS 357
RESULTS AND DISCUSSION 357
CONCLUSIONS 358
REFERENCES 358
Chapter 62. AEROSOLIZATION OF LIPOSOMAL (AMBISOME®) AND NON-LIPOSOMAL (FUNGIZONE®) AMPHOTERICIN B AS A TREATMENT FOR PULMONARY FUNGAL INFECTIONS. 359
INTRODUCTION 359
OBJECTIVES 359
METHODS 359
CONCLUSION 361
Chapter 63. EFFICACY OF AEROSOLIZED UPOSOMAL AMPHOTERICIN B (AMBISOME®) AS A PROPHOLACTIC TREATMENT IN AN IMMUNE COMPROMISED MURINE MODEL OF PULMONARY ASPERGILLOSIS. 362
INTRODUCTION 362
OBJECTIVES 362
METHODS 362
RESULTS 362
CONCLUSION 360
Chapter 64. EFFICACY OF ALBENDAZOLE ADMINISTERED ORALLY IS IMPROVED BY ENCAPSULATION IN LIPOSOMES 363
INTRODUCTION 363
EXPERIMENTAL 363
RESULTS AND DISCUSSION 364
CONCLUSION 364
REFERENCES 364
Chapter 65. LIPID NANO-SPHERE(LNS), A PROTEIN-FREE ANALOGUE OF LIPOPROTEINS, AS A NOVEL DRUG CARRIER FOR PARENTERAL ADMINISTRATION. IV. 365
INTRODUCTION 365
EXPERIMENTAL METHODS 365
RESULTS AND DISCUSSION 366
CONCLUSION 366
REFERENCES 366
Chapter 66. MICROENCAPSULATION OF MITOMYCIN C FOR CONTROLLED DELIVERY AND TARGETING 367
INTRODUCTION 367
METHODS 367
RESULTS AND DISCUSSION 367
CONCLUSIONS 368
REFERENCES 368
ACKNOWLEDGEMENTS 368
AFFILIATION 368
Author Index Volume 28 370
Subject Index Volume 28 372

Produkt-Details

• Erscheint lt. Verlag: 22.10.2013
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Gesundheitsfachberufe
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie
• Themenwelt: Studium ► 2. Studienabschnitt (Klinik) ► Pharmakologie / Toxikologie
• Themenwelt: Technik
• ISBN-10: 1-4831-6157-9 / 1483161579
• ISBN-13: 978-1-4831-6157-0 / 9781483161570