Description
Book SynopsisChitosan is a linear polysaccharide commercially produced by the deacetylation of chitin. It is non-toxic, biodegradable, biocompatible, and acts as a bioadhesive with otherwise unstable biomolecules - making it a valuable component in the formulation of biopharmaceutical drugs.
Chitosan-Based Systems for Biopharmaceuticals provides an extensive overview of the application of chitosan and its derivatives in the development and optimisation of biopharmaceuticals. The book is divided in four different parts. Part I discusses general aspects of chitosan and its derivatives, with particular emphasis on issues related to the development of biopharmaceutical chitosan-based systems. Part II deals with the use of chitosan and derivatives in the formulation and delivery of biopharmaceuticals, and focuses on the synergistic effects between chitosan and this particular subset of pharmaceuticals. Part III discusses specific applications of chitosan and its derivatives for biopharmaceuti
Table of Contents
List of Contributors xvii
Foreword xxiii
Marıa Jose Alonso
Preface xxv
Acknowledgments xxvii
Part One General Aspects of Chitosan 1
1 Chemical and Technological Advances in Chitins and Chitosans Useful for the Formulation of Biopharmaceuticals 3
Riccardo A. A. Muzzarelli
1.1 Introduction 3
1.2 Safety of Chitins and Chitosans 4
1.3 Ionic Liquids: New Solvents and Reaction Media 5
1.4 Chitin and Chitosan Nanofibrils 8
1.5 Electrospun Nanofibers 10
1.6 Polyelectrolyte Complexes and Mucoadhesion 12
1.7 Conclusions and Future Perspectives 16
2 Physical Properties of Chitosan and Derivatives in Sol and Gel States 23
Marguerite Rinaudo
2.1 Introduction 23
2.2 Chitin 24
2.3 Chitosan 28
2.4 Conclusions and Future Perspectives 36
3 Absorption Promotion Properties of Chitosan and Derivatives 45
Akira Yamamoto
3.1 Introduction 45
3.2 Effect of Chitosan on the Intestinal Absorption of Poorly Absorbable Drugs 47
3.3 Effect of Chitosan Derivatives on the Intestinal Absorption of Poorly Absorbable Drugs 47
3.4 Effect of Chitosan Oligomers on the Intestinal Absorption of Poorly Absorbable Drugs 48
3.5 Colon-Specific Delivery of Insulin Using Chitosan Capsules 51
3.6 Conclusions and Future Perspectives 54
4 Biocompatibility and Biodegradation of Chitosan and Derivatives 57
Ahmad Sukari Halim, Lim Chin Keong, Ismail Zainol, and Ahmad Hazri Abdul Rashid
4.1 Introduction 57
4.2 Biocompatibility Evaluation of Chitosan and Derivatives 58
4.3 Biodegradation of Chitosan and Derivatives 65
4.4 Conclusions and Future Perspectives 69
5 Biological and Pharmacological Activity of Chitosan and Derivatives 75
Teresa Cunha, Branca Teixeira, Barbara Santos, Marlene Almeida, Gustavo Dias, and Jose das Neves
5.1 Introduction 75
5.2 Biological Activity 76
5.3 Chitosan's Usefulness in Therapy and Alternative Medicine 82
5.4 Conclusions and Future Perspectives 84
6 Biological, Chemical, and Physical Compatibility of Chitosan and Biopharmaceuticals 93
Masayuki Ishihara, Masanori Fujita, Satoko Kishimoto, Hidemi Hattori, and Yasuhiro Kanatani
6.1 Introduction 93
6.2 Structural Features of Chitosan and Its Derivatives 94
6.3 Biocompatibility for Chitosan and Its Derivatives 95
6.4 Biocompatibility of Photo-Cross-Linkable Chitosan Hydrogel 98
6.5 Physical and Chemical Compatibility of Chitosan and Its Derivatives 100
6.6 Conclusions and Future Perspectives 102
7 Approaches for Functional Modification or Cross-Linking of Chitosan 107
A. Anitha, N. Sanoj Rejinold, Joel D. Bumgardner, Shanti V. Nair, and Rangasamy Jayakumar
7.1 Introduction 107
7.2 General Awareness of Chitosan Cross-Linking Methods 108
7.3 Modified Chitosan: Synthesis and Characterization 112
7.4 Applications of Modified Chitosan and Its Derivatives in Drug Delivery 118
7.5 Conclusions and Future Perspectives 118
Part Two Biopharmaceuticals Formulation and Delivery Aspects Using Chitosan and Derivatives 125
8 Use of Chitosan and Derivatives in Conventional Biopharmaceutical Dosage Forms Formulation 127
Teofilo Vasconcelos, Pedro Barrocas, and Rui Cerdeira
8.1 Introduction 127
8.2 Advantageous Properties of Chitosan and Its Derivatives 128
8.3 Oral Administration 129
8.4 Buccal Administration 131
8.5 Nasal Administration 132
8.6 Pulmonary Administration 132
8.7 Transdermal Administration 133
8.8 Conclusions and Future Perspectives 133
9 Manufacture Techniques of Chitosan-Based Microparticles and Nanoparticles for Biopharmaceuticals 137
Franca Ferrari, M. Cristina Bonferoni, Silvia Rossi, Giuseppina Sandri, and Carla M. Caramella
9.1 Introduction 137
9.2 Water-in-Oil Emulsion and Chemical Cross-linking 138
9.3 Drying Techniques 141
9.4 Ionic Cross-linking Methods 144
9.5 Coacervation and Precipitation Method 151
9.6 Direct Interaction between Chitosan and Biopharmaceuticals 152
9.7 Conclusions and Future Perspectives 153
10 Chitosan and Derivatives for Biopharmaceutical Use: Mucoadhesive Properties 159
Katharina Leithner and Andreas Bernkop-Schnurch
10.1 Introduction 159
10.2 Mucoadhesion 160
10.3 Chitosan and Its Derivatives 161
10.4 Biopharmaceutical Use of Chitosan and Its Derivatives 171
10.5 Conclusions and Future Perspectives 175
11 Chitosan-Based Systems for Mucosal Delivery of Biopharmaceuticals 181
Sonia Al-Qadi, Ana Grenha, and Carmen Remunan-Lopez
11.1 Introduction 181
11.2 Important Challenges for the Delivery of Biopharmaceuticals by Mucosal Routes 182
11.3 Interest in Chitosan for Mucosal Delivery of Biopharmaceuticals 184
11.4 Chitosan-Based Delivery Nanosystems for Mucosal Delivery of Biopharmaceuticals 188
11.5 Conclusions and Future Perspectives 200
12 Chitosan-Based Delivery Systems for Mucosal Vaccination 211
Gerrit Borchard, Farnaz Esmaeili, and Simon Heuking
12.1 Introduction 211
12.2 Adjuvant Properties of Chitosan 212
12.3 Chitosan in the Delivery of Protein and Subunit Vaccines 213
12.4 Chitosan-Based Formulations of DNAVaccines 215
12.5 Vaccine Formulations Using Chitosan in Combination with Other Polymers 216
12.6 Chitosan Derivatives in Vaccine Carrier Design 217
12.7 Conclusions and Future Perspectives 220
13 Chitosan-Based Nanoparticulates for Oral Delivery of Biopharmaceuticals 225
Filipa Antunes, Fernanda Andrade, and Bruno Sarmento
13.1 Introduction 225
13.2 Challenges on the Oral Delivery of Therapeutic Proteins 226
13.3 Challenges on the Oral Delivery of Genetic Material 227
13.4 Role of Chitosan in the Protection of Biopharmaceuticals in the Gastrointestinal Tract 229
13.5 Chitosan-Based Nanoparticles for Oral Delivery of Therapeutic Proteins 232
13.6 Chitosan-Based Nanoparticles for Oral Delivery of Genetic Material 234
13.7 Conclusions and Future Perspectives 236
14 Chitosan-Based Systems for Ocular Delivery of Biopharmaceuticals 243
Suresh P. Vyas, Rishi Paliwal, and Shivani Rai Paliwal
14.1 Introduction 243
14.2 Ocular Delivery of Biopharmaceuticals 244
14.3 Chitosan: A Suitable Biomaterial for Ocular Therapeutics 244
14.4 Chitosan-Based Systems for Ocular Delivery of Biomacromolecules 245
14.5 Toxicological and Compatibility Aspects of Chitosan-Based Ocular Systems 249
14.6 Conclusions and Future Perspectives 250
15 Chemical Modification of Chitosan for Delivery of DNA and siRNA 255
You-Kyoung Kim, Hu-Lin Jiang, Ding-Ding Guo, Yun-Jaie Choi, Myung-Haing Cho, Toshihiro Akaike, and Chong-Su Cho
15.1 Introduction 255
15.2 Hydrophilic Modification 256
15.3 Hydrophobic Modification 257
15.4 Specific Ligand Modification 259
15.5 pH-Sensitive Modification 264
15.6 Conclusions and Future Perspectives 269
Part Three Advanced Application of Chitosan and Derivatives for Biopharmaceuticals 275
16 Target-Specific Chitosan-Based Nanoparticle Systems for Nucleic Acid Delivery 277
Shardool Jain and Mansoor Amiji
16.1 Introduction 277
16.2 Chitosan-Based Nanoparticle Delivery Systems 283
16.3 Illustrative Examples of DNAVaccine Delivery 286
16.4 Illustrative Examples of Nucleic Acid Delivery Systems for Cancer Therapy 288
16.5 Illustrative Examples of Nucleic Acid Delivery Systems for Anti-Inflammatory Therapy 291
16.6 Conclusions and Future Perspectives 294
17 Functional PEGylated Chitosan Systems for Biopharmaceuticals 301
Hee-Jeong Cho, Goen Kim, Hyeok-Seung Kwon, and Yu-Kyoung Oh
17.1 Introduction 301
17.2 PEGylated Chitosan for the Delivery of Proteins and Peptides 304
17.3 PEGylated Chitosan for Delivery of Nucleic Acids 308
17.4 PEGylated Chitosan for Delivery of Other Macromolecular Biopharmaceuticals 311
17.5 PEGylated Chitosan Used for Cellular Scaffolds 313
17.6 Conclusions and Future Perspectives 313
18 Stimuli-Sensitive Chitosan-Based Systems for Biopharmaceuticals 319
Cuiping Zhai, Jinfang Yuan, and Qingyu Gao
18.1 Introduction 319
18.2 pH-Sensitive Chitosan-Based Systems 319
18.3 Thermosensitive Chitosan-Based Systems 321
18.4 pH-Sensitive and Thermosensitive Chitosan-Based Systems 323
18.5 pH- and Ionic-Sensitive Chitosan-Based Systems 325
18.6 Photo-Sensitive Chitosan-Based Systems 325
18.7 Electrical-Sensitive Chitosan-Based Systems 326
18.8 Magnetic-Sensitive Chitosan-Based Systems 326
18.9 Chemical Substance-Sensitive Chitosan-Based Systems 327
18.10 Conclusions and Future Perspectives 327
19 Chitosan Copolymers for Biopharmaceuticals 333
Ramon Novoa-Carballal, Ricardo Riguera, and Eduardo Fernandez-Megia
19.1 Introduction 333
19.2 Chitosan-g-Poly(Ethylene Glycol) 337
19.3 Chitosan-g-Polyethylenimine 347
19.4 Other Copolymers of Chitosan 357
19.5 Copolymers of Chitosan with Promising Applications 363
19.6 Conclusions and Future Perspectives 368
20 Application of Chitosan for Anticancer Biopharmaceutical Delivery 381
Claudia Philippi, Brigitta Loretz, Ulrich F. Schaefer, and Claus-Michael Lehr
20.1 Introduction 381
20.2 Chitosan and Cancer: Intrinsic Antitumor Activity of the Polymer Itself 382
20.3 Chitosan Formulations Developed for Classic Anticancer Drugs 383
20.4 Biopharmaceuticals Delivered by Chitosan Preparations 384
20.5 Active Targeting Strategies and Multifunctional Chitosan Formulations 388
20.6 Conclusions and Future Perspectives 389
21 Chitosan-Based Biopharmaceutical Scaffolds in Tissue Engineering and Regenerative Medicine 393
Tao Jiang, Meng Deng, Wafa I. Abdel- Fattah, and Cato T. Laurencin
21.1 Introduction 393
21.2 Fabrication of Chitosan-Based Biopharmaceuticals Scaffolds 395
21.3 Applications of Chitosan-Based Biopharmaceutical Scaffolds in Tissue Engineering and Regenerative Medicine 403
21.4 Future Trends: Regenerative Engineering 416
21.5 Conclusions and Future Perspectives 417
22 Wound-Healing Properties of Chitosan and Its Use in Wound Dressing Biopharmaceuticals 429
Tyler G. St. Denis, Tianhong Dai, Ying-Ying Huang, and Michael R. Hamblin
22.1 Introduction 429
22.2 Brief Review of Wound Repair 430
22.3 Wound-Healing Effects of Chitosan 433
22.4 Chitosan for Wound Therapeutics Delivery 440
22.5 Conclusions and Future Perspectives 444
Part Four Regulatory Status, Toxicological Issues, and Clinical Perspectives 451
23 Toxicological Properties of Chitosan and Derivatives for Biopharmaceutical Applications 453
Thomas J. Kean and Maya Thanou
23.1 Introduction 453
23.2 In Vitro Toxicity of Chitosan and Derivatives 454
23.3 In Vivo Toxicity of Chitosan and Derivatives 457
23.4 Conclusions and Future Perspectives 459
24 Regulatory Status of Chitosan and Derivatives 463
Michael Dornish, David S. Kaplan, and Sambasiva R. Arepalli
24.1 Introduction 463
24.2 Source 464
24.3 Characterization 464
24.4 Purity 465
24.5 Applications of Advanced Uses of Chitosan 466
24.6 Regulatory Considerations for Chitosan and Chitosan Derivatives in the European Union, and Medical Devices or Combination Products with Medical Device (CDRH) Lead 468
24.7 Regulatory Pathways 469
24.8 Chitosan Medical Products: US Regulatory Review Processes for Medical Devices or Combination Products with CDRH Lead 469
24.9 Chitosan Wound Dressings 470
24.10 The European Regulatory System: The European Medicines Agency (EMA) and European Directorate for the Quality of Medicines (EDQM) 474
24.11 Further Regulatory Considerations 475
24.12 Conclusions and Future Perspectives 477
24.13 Disclaimer 478
25 Patentability and Intellectual Property Issues Related to Chitosan-Based Biopharmaceutical Products 483
Mafalda Videira and Rogerio Gaspar
25.1 Introduction 483
25.2 Setting the Scene: The Role of Chitosan as a Pharmaceutical Excipient 484
25.3 Addressing the Drivers for Scientific Progress on Chitosan: Innovation and Inventability 495
25.4 Conclusions and Future Perspectives 496
26 Quality Control and Good Manufacturing Practice (GMP) for Chitosan-Based Biopharmaceutical Products 503
Torsten Richter, Maika Gulich, and Katja Richter
26.1 Introduction 504
26.2 Regulatory Requirements for Production 505
26.3 Manufacturing GMP: Fundamental Considerations 508
26.4 Requirements for Rooms, Personnel, and Equipment 511
26.5 Qualification and Validation 511
26.6 Quality Control 513
26.7 Monitoring and Maintenance of a GMP System 519
26.8 Conclusions and Future Perspectives 522
27 Preclinical and Clinical Use of Chitosan and Derivatives for Biopharmaceuticals: From Preclinical Research to the Bedside 525
David A. Zaharoff, Michael Heffernan, Jonathan Fallon, and John W. Greiner
27.1 Introduction 525
27.2 Chitosan as a Parenteral (Subcutaneous) Vaccine Platform 526
27.3 Chitosan as an Immunotherapeutic Platform 530
27.4 Conclusions and Future Perspectives 537
References 539
Index 543
