FOREWORD ....................................................... xi
PREFACE ...................................................... xiii
CONTRIBUTORS ................................................... xv
PART I INTRODUCTION ............................................ 1
1 FUNDAMENTALS OF DRUG DELIVERY ................................ 3
Rebecca A. Bader
1.1 Introduction: History and Future of Drug Delivery ....... 3
1.2 Terminology ............................................. 5
1.3 Basic Pharmacokinetics .................................. 8
1.4 Basic Pharmacodynamics ................................. 12
1.5 Mass Transfer .......................................... 13
1.6 Key Points ............................................. 23
1.7 Homework Problems ...................................... 23
2 CHALLENGES OF DRUG DELIVERY ................................. 29
Patricia R. Wardwell and Rebecca A. Bader
2.1 Introduction ........................................... 29
2.2 History and Challenges of Drug Delivery ................ 30
2.3 Physical Barriers ...................................... 31
2.4 Metabolic and Chemical Concerns ........................ 39
2.5 Physical Properties of Therapeutics .................... 42
2.6 Polymer Carriers as a Solution to Challenges ........... 45
2.7 Key Points ............................................. 50
2.8 Homework Problems ...................................... 50
PART II INJECTABLE POLYMERIC DRUG DELIVERY SYSTEMS ............. 55
3 POLYMER-DRUG CONJUGATES ..................................... 57
Cristina Fante and Francesca Greco
3.1 Introduction ........................................... 57
3.2 Historical Perspective ................................. 58
3.3 Polymer-Drug Conjugates: Biological Rationale .......... 59
3.4 Structural Features of Polymer-Drug Conjugates ......... 62
3.5 Making a Polymer-Drug Conjugate ........................ 68
3.6 Current Challenges and Future Perspectives ............. 71
3.7 Key Points ............................................. 75
3.8 Worked Example ......................................... 76
3.9 Homework Problems ...................................... 76
4 POLYMERIC MICROPARTICLES .................................... 85
Noelle K. Comolli and Colleen E. Clark
4.1 Introduction ........................................... 85
4.2 The Rationale for Microparticles ....................... 86
4.3 Defining the Design Criteria ........................... 87
4.4 Polymer Selection ...................................... 89
4.5 Microparticle Synthesis ................................ 91
4.6 Microparticle Characterization Methods ................. 96
4.7 Drag Release from Microparticles ...................... 100
4.8 Microparticle Design Examples ......................... 108
4.9 Key Points ............................................ 110
4.10 Worked Example ........................................ 110
4.11 Homework Problems ..................................... 111
5 POLYMERIC NANOPARTICLES .................................... 117
Andrew L. Vasilakes, Thomas D. Dziubla, and Paritosh
P. Wattamwar
5.1 Introduction .......................................... 117
5.2 PNP Design ............................................ 124
5.3 PNP Formulation Methods and Targeting ................. 128
5.4 Nanoparticle Targeting Overview ....................... 133
5.5 PNP Characterization .................................. 139
5.6 Major Clinical Achievements ........................... 147
5.7 Key Points ............................................ 148
5.8 Worked Example ........................................ 149
5.9 Homework Problems ..................................... 150
6 BLOCK COPOLYMER MICELLES AND VESICLES FOR DRUG DELIVERY .... 163
James D. Robertson, Nisa Patikarnmonthon, Adrian S.
Joseph, and Giuseppe Battaglia
6.1 Introduction .......................................... 163
6.2 Drug Encapsulation and Release ........................ 165
6.3 Bioavailability and Biodistribution ................... 166
6.4 Stimuli Responsiveness ................................ 170
6.5 The Immune System ..................................... 174
6.6 Gene Therapy .......................................... 177
6.7 Cancer Therapy ........................................ 180
6.8 Conclusions ........................................... 182
6.9 Key Points ............................................ 182
6.10 Homework Problems ..................................... 183
PART III IMPLANTABLE POLYMERIC DRUG DELIVERY SYSTEMS .......... 189
7 IMPLANTABLE DRUG DELIVERY SYSTEMS .......................... 191
Luis Solorio, Angela Carlson, Haoyan Zhou, and Agata
A. Exner
7.1 Introduction .......................................... 191
7.2 Nondegradable Polymeric Implants ...................... 193
7.3 Biodegradable Polymeric Implants ...................... 198
7.4 Conclusions and Future Perspectives ................... 215
7.5 Key Points ............................................ 216
7.6 Homework Problems ..................................... 216
8 POLYMERIC DRUG DELIVERY SYSTEMS IN TISSUE ENGINEERING ...... 227
Matthew Skiles and James Blanchette
8.1 Introduction .......................................... 227
8.2 Wound Healing as a Prototype for Adult Tissue
Generation ............................................ 228
8.3 Bioactive Factors in Tissue Engineering and
Regenerative Medicine ................................. 232
8.4 Delivery of Growth Factors in Tissue Engineering
and Regenerative Medicine ............................. 248
8.5 Key Points ............................................ 268
8.6 Worked Example ........................................ 269
8.7 Homework Problems ..................................... 270
PART IV ORAL POLYMERIC DRUG DELIVERY SYSTEMS .................. 283
9 ORAL CONTROLLED-RELEASE POLYIVIERIC DRUG DELIVERY SYSTEMS .. 285
James W. McGinity, James C. DiNunzio, and Justin M. Keen
9.1 Introduction .......................................... 285
9.2 Release Mechanisms of Oral Polymeric Dosage Forms ..... 288
9.3 Oral Polymeric Release Modifiers ...................... 295
9.4 Manufacturing Technologies and Industrial
Applications of Controlled Release .................... 297
9.5 Worked Example ........................................ 311
9.6 Key Points ............................................ 314
9.7 Homework Problems ..................................... 314
10 MUCOADHESIVE DRUG DELIVERY SYSTEMS ......................... 319
Srinath Muppalaneni, David Mastropietro, and Hossein
Omidian
10.1 Introduction ......................................... 319
10.2 Factors Affecting Mucoadhesion ....................... 320
10.3 Polymer-Mucus Interactions ........................... 320
10.4 Mucoadhesion Mechanisms .............................. 322
10.5 Mucoadhesive Polymers ................................ 324
10.6 Novel Mucoadhesive Materials ......................... 327
10.7 Mucoadhesion Testing ................................. 330
10.8 Drug Release Studies ................................. 332
10.9 Mucoadhesive Dosage Forms ............................ 332
10.10 Conclusion ........................................... 334
10.11 Key Points ........................................... 334
10.12 Homework Questions ................................... 337
11 ENHANCED ORAL DRUG DELIVERY THROUGH METABOLIC PATHWAYS ..... 343
Gregory Russell-Jones
11.1 Introduction .......................................... 343
11.2 Uptake of Nutrients from the Intestine ................ 344
11.3 Nutrient Transport in the Intestine ................... 349
11.4 Use of Nutrient Transporters for Drug Delivery ........ 352
11.5 Case Study: The Use of the Vitamin B2 Uptake System
for Drug Delivery ..................................... 352
11.6 Key Points ............................................ 365
11.7 Worked Example ........................................ 365
11.8 Homework Problems ..................................... 366
PART V ADVANCED POLYMERIC DRUG DELIVERY ....................... 375
12 STIMULI-RESPONSIVE POLYMER DELIVERY SYSTEMS ................ 377
Amy Van Hove, Zhanwu Cui, and Danielle S.W. Benoit
12.1 Introduction .......................................... 377
12.2 Temperature-Responsive Polymers for Drug Delivery ..... 378
12.3 pH-Responsive Polymers for Drug Delivery .............. 387
12.4 Reduction/Oxidation (Redox)-Responsive Polymers ....... 397
12.5 Enzymatically Responsive Drug Delivery ................ 403
12.6 Key Points ............................................ 415
12.7 Homework Questions .................................... 416
13 AFFINITY-BASED DRUG DELIVERY ............................... 429
Andrew S. Fu and Horst A. von Recum
13.1 Introduction .......................................... 429
13.2 Association Constant .................................. 430
13.3 Worked Example ........................................ 432
13.4 Affinity-Based Drug Delivery Systems .................. 437
13.5 Mathematical Modeling of Affinity-Based Systems ....... 444
13.6 Challenges and Future Directions ...................... 448
13.7 Key Points ............................................ 448
13.8 Homework Problems ..................................... 449
INDEX ......................................................... 453
|
