Engineering Polymer Systems for Improved Drug Delivery

Polymers have played a critical role in the rational design and application of drug delivery systems that increase the efficacy and reduce the toxicity of new and conventional therapeutics. Beginning with an introduction to the fundamentals of drug delivery, Engineering Polymer Systems for Improved Drug Delivery explores traditional drug delivery techniques as well as emerging advanced drug delivery techniques. By reviewing many types of polymeric drug delivery systems, and including key points, worked examples and homework problems, this book will serve as a guide to for specialists and non-specialists as well as a graduate level text for drug delivery courses.

REBECCA A. BADER, PhD, is Assistant Professor in the Department of Biomedical & Chemical Engineering at Syracuse University and resident member of the Syracuse Biomaterials Institute. Combining her expertise in chemistry and materials science, Dr. Bader's current research focuses on the development of polysaccharide-based carrier systems for targeted delivery in the treatment of rheumatoid arthritis, biofilm-related diseases, cancer, and vascular diseases.

DAVID A. PUTNAM, PhD, is Associate Professor in the College of Engineering at Cornell University. His research is dedicated to the rational design and synthesis of functional biomaterials to facilitate targeted and controlled drug delivery. Dr. Putnam is a Fellow of the Coulter Foundation and the American Institute for Medical and Biological Engineering, an honor bestowed upon the top 2% of biomedical engineers in the United States.

Part I: Introduction

Chapter 1 Fundamentals of Drug Delivery 1-1
Rebecca Bader

1.1 Introduction: History & Future of Drug Delivery 1-1

1.2 Terminology 1-4

1.3 Basic Pharmacokinetics 1-11

1.4 Basic Pharmacodynamics 1-17

1.5 Mass Transfer 1-19

1.6 Key Points 1-32

1.7 Homework Problems 1-32

Chapter 2 Challenges of Drug Delivery 2-1
Patricia R. Wardwell and Rebecca Bader

2.1 Introduction 2-1

2.2 History and Challenges of Drug Delivery 2-2

2.3 Physical Barriers 2-4

2.4 Metabolic and Chemical Concerns 2-14

2.5 Physical Properties of Therapeutics 2-18

2.6 Polymer Carriers as a Solution to Challenges 2-21

2.7 Key Points 2-27

2.8 Homework Problems 2-28

Part II: Injectable Polymeric Drug Delivery Systems

Chapter 3 Polymer-Drug Conjugates 3-1
Cristina Fante and Francesca Greco

3.1 Introduction 3-1

3.2 Historical perspective 3-2

3.3 Polymer-drug conjugates: biological rationale 3-4

3.4 Structural features of polymer-drug conjugates 3-10

3.5 Making a polymer-drug conjugate 3-23

3.6 Current challenges and future perspectives 3-32

3.7 Key Points 3-40

3.8 Worked Examples 3-41

3.9 Homework Problems 3-42

Chapter 4 Polymeric Microparticles 4-1
Colleen E. Clark and Noelle K. Comolli

4.1 Introduction 4-1

4.2 The rationale for microparticles 4-2

4.3 Defining the design criteria 4-7

4.4 Polymer selection 4-10

4.5 Microparticle synthesis 4-16

4.6 Microparticle characterization methods 4-25

4.7 Drug release from microparticles 4-33

4.8 Microparticle design examples 4-55

4.9 Key Points 4-56

4.10 Worked Example 4-58

4.11 Homework Problems 4-60

Chapter 5 Polymeric Nanoparticles 5-1
Andrew L. Vasilakes, Thomas D. Dziubla, and Paritosh P. Wattamwar

5.1 Introduction 5-1

5.2 PNP Design 5-10

5.3 PNP Formulation Methods and Targeting 5-15

5.4 Nanoparticle Targeting Overview 5-22

5.5 PNP Characterization 5-30

5.6 Major Clinical Achievements 5-41

5.7 Key Points 5-42

5.8 Worked Example 5-44

5.9 Homework Problems 5-45

Chapter 6 Polymeric Micelles & Vesicles 6-1
James D Robertson, Nisa Patikarnmonthon, Adrian S Joseph, and Giuseppe Battaglia

6.1 Introduction 6-1

6.2 Drug Encapsulation and Release 6-3

6.3 Bioavailability and Biodistribution 6-7

6.4 Stimuli Responsiveness 6-11

6.5 The Immune System 6-16

6.6 Gene Therapy 6-20

6.7 Cancer Therapy 6-24

6.8 Conclusions 6-26

6.9 Key Points 6-26

6.10 Homework Problems 6-27

Part III: Implantable Polymeric Drug Delivery Systems

Chapter 7 Polymeric Implants 7-1
Luis Solorio, Angela Carlson, Haoyan Zhou and Agata A. Exner

7.1 Overview 7-1

7.2 Non-Degradable Polymeric Implant 7-5

7.3 Biodegradable Polymeric Implants 7-17

7.4 Conclusions and Future Perspectives 7-51

7.5 Key Points 7-53

7.6 Homework Problems 7-53

Chapter 8 Polymeric Drug Delivery Systems in Tissue Engineering 8-1
Matthew Skiles and James Blanchette

8.1 Introduction 8-1

8.2 Wound healing as a prototype for adult tissue generation 8-2

8.3 Bioactive factors in tissue engineering and regenerative medicine.8-8

8.4 Delivery of growth factors in tissue engineering and regenerative Medicine 8-25

8.5 Key Points 8-54

8.6 Worked Example 8-56

8.7 Homework Problems 8-56

Part IV: Oral Polymeric Drug Delivery Systems

Chapter 9 Oral Controlled Release Polymeric Drug Delivery Systems 9-1
James W. McGinity, James C. DiNunzio and Justin M. Keen

9.1 Introduction 9-1

9.2 Release mechanisms of oral polymeric dosage forms 9-9

9.3 Oral polymeric release modifiers 9-23

9.4 Manufacturing technologies and industrial applications of controlled release 9-27

9.5 Worked Examples 9-61

9.6 Key Points 9-65

9.7 Homework Problems 9-65

Chapter 10 Mucoadhesive Drug Delivery Systems 10-1
Srinath Muppalaneni, David Mastropietro, and Hossein Omidian

10.1 Introduction 10-1

10.2 Factors Affecting Mucoadhesion 10-1

10.3 Polymer-Mucus Interactions 10-3

10.4 Mucoadhesion Mechansims 10-5

10.5 Mucoadhesive Polymers 10-7

10.6 Novel Mucoadhesive Materials 10-14

10.7 Mucoadhesion Testing 10-16

10.8 Drug Release Studies 10-19

10.9 Mucoadhesive Dosage Forms 10-19

10.10 Conclusion 10-26

10.11 Key Points 10-27

10.12 Homework Questions 10-27

Chapter 11 Enhanced Drug Delivery through Metabolic Pathways 11-1
Gregory Russell-Jones

11.1 Introduction 11-1

11.2 Uptake of Nutrients from the Intestine 11-2

11.3 Nutrient Transport in the Intestine 11-13

11.4 Use of Nutrient Transporters for Drug Delivery 11-16

11.5 Case Study: The use of the Vitamin B12 Uptake System for Drug Delivery 11-19

11.6 Key Points 11-34

11.7 Worked Example 11-34

11.8 Homework Problems 11-37

Part V: Advanced Polymeric Drug Delivery

Chapter 12 Stimuli-Responsive Polymers 12-1
Amy Van Hove, Zhanwu Cui, and Danielle S.W. Benoit

12.1 Introduction 12-1

12.2 Temperature-Responsive Polymers for Drug Delivery 12-2

12.3 pH Responsive Polymers for Drug Delivery 12-18

12.4 Reduction/oxidation (Redox)-Responsive Polymer 12-41

12.5 Enzymatically-responsive drug delivery 12-54

12.6 Key Points 12-82

12.7 Homework Questions 12-83

Chapter 13 Affinity-Based Drug Delivery 13-1
Andrew S. Fu and Horst A. von Recum

13.1 Introduction 13-1

13.2 Association Contrast 13-3

13.3 Affinity-Based Drug Delivery Systems 13-15

13.4 Mathematical Modeling of Affinity Based Systems 13-31

13.5 Challenges and Future Directions 13-38

13.6 Key Points 13-40

13.7 Homework Problems 13-40

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