Chitosan-Based Systems for Biopharmaceuticals Delivery, Targeting and Polymer Therapeutics

by Sarmento, Bruno; Das Neves, Jose

• ISBN13: 9780470978320
• ISBN10: 0470978325
• Edition: 1st
• Format: Hardcover
• Copyright: 2012-03-05
• Publisher: Wiley

Summary

Chitosan is a linear polysaccharide produced commercially 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 derivatives, with particular emphasis on issues related to the development of biopharmaceutical chitosan-based systems, comprising a useful background for the following chapters. 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 continues and complements the previous part by discussing in detail specific applications of chitosan and/or some particular derivatives for biopharmaceutical use. Finally, Part IV presents diverse viewpoints on different issues such as regulatory, manufacturing and toxicological requirements of chitosan and its derivatives related with the development of biopharmaceutical products, as well as their patent status, and clinical application and potential. Topics covered include: chemical and technological advances in chitins and chitosans useful for the formulation of biopharmaceuticals physical properties of chitosan and derivatives in sol and gel states absorption promotion properties of chitosan and derivatives biocompatibility and biodegradation of chitosan and derivatives biological and pharmacological activity of chitosan and derivatives biological, chemical and physical compatibility of chitosan and biopharmaceuticals approaches for functional modification or crosslinking of chitosan use of chitosan and derivatives in conventional biopharmaceutical dosage forms formulation manufacture techniques of chitosan-based microparticles and nanoparticles for biopharmaceuticals chitosan and derivatives for biopharmaceutical use: mucoadhesive properties chitosan-based systems for mucosal delivery of biopharmaceuticals chitosan-based delivery systems for mucosal vaccination chitosan-based nanoparticulates for oral delivery of biopharmaceuticals chitosan-based systems for ocular delivery of biopharmaceuticals chemical modification of chitosan for delivery of DNA and siRNA target-specific chitosan-based nanoparticle systems for nucleic acid delivery functional PEGylated chitosan systems for biopharmaceuticals stimuli-sensitive chitosan-based systems for biopharmaceuticals chitosan copolymers for biopharmaceuticals application of chitosan for anti-cancer biopharmaceutical delivery chitosan-based biopharmaceuticals scaffolds in tissue engineering and re

Author Biography

Bruno Sarmento, Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Porto, Portugal & CICS, Department of Pharmaceutical Sciences, Instituto Superior de Ciências da Saúde–Norte, Gandra, Portugal

José das Neves, Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Porto, Portugal

Table of Contents

List of Contributors	p. xvii
Foreword	p. xxiii
Preface	p. xxv
Acknowledgments	p. xxvii
General Aspects of Chitosan	p. 1
Chemical and Technological Advances in Chitins and Chitosans Useful for the Formulation of Biopharmaceuticals	p. 3
Introduction	p. 3
Safety of Chitins and Chitosans	p. 4
Ionic Liquids: New Solvents and Reaction Media	p. 5
Chitin and Chitosan Nanofibrils	p. 8
Electrospun Nanofibers	p. 10
Polyelectrolyte Complexes and Mucoadhesion	p. 12
Conclusions and Future Perspectives	p. 16
Physical Properties of Chitosan and Derivatives in Sol and Gel States	p. 23
Introduction	p. 23
Chitin	p. 24
Chitosan	p. 28
Conclusions and Future Perspectives	p. 36
Absorption Promotion Properties of Chitosan and Derivatives	p. 45
Introduction	p. 45
Effect of Chitosan on the Intestinal Absorption of Poorly Absorbable Drugs	p. 47
Effect of Chitosan Derivatives on the Intestinal Absorption of Poorly Absorbable Drugs	p. 47
Effect of Chitosan Oligomers on the Intestinal Absorption of Poorly Absorbable Drugs	p. 48
Colon-Specific Delivery of Insulin Using Chitosan Capsules	p. 51
Conclusions and Future Perspectives	p. 54
Biocompatibility and Biodegradation of Chitosan and Derivatives	p. 57
Introduction	p. 57
Biocompatibility Evaluation of Chitosan and Derivatives	p. 58
Biodegradation of Chitosan and Derivatives	p. 65
Conclusions and Future Perspectives	p. 69
Biological and Pharmacological Activity of Chitosan and Derivatives	p. 75
Introduction	p. 75
Biological Activity	p. 76
Chitosan's Usefulness in Therapy and Alternative Medicine	p. 82
Conclusions and Future Perspectives	p. 84
Biological, Chemical, and Physical Compatibility of Chitosan and Biopharmaceuticals	p. 93
Introduction	p. 93
Structural Features of Chitosan and Its Derivatives	p. 94
Biocompatibility for Chitosan and Its Derivatives	p. 95
Biocompatibility of Photo-Cross-Linkable Chitosan Hydrogel	p. 98
Physical and Chemical Compatibility of Chitosan and Its Derivatives	p. 100
Conclusions and Future Perspectives	p. 102
Approaches for Functional Modification or Cross-Linking of Chitosan	p. 107
Introduction	p. 107
General Awareness of Chitosan Cross-Linking Methods	p. 108
Modified Chitosan: Synthesis and Characterization	p. 112
Applications of Modified Chitosan and Its Derivatives in Drug Delivery	p. 118
Conclusions and Future Perspectives	p. 118
Biopharmaceuticals Formulation and Delivery Aspects Using Chitosan and Derivatives	p. 125
Use of Chitosan and Derivatives in Conventional Biopharmaceutical Dosage Forms Formulation	p. 127
Introduction	p. 127
Advantageous Properties of Chitosan and Its Derivatives	p. 128
Oral Administration	p. 129
Buccal Administration	p. 131
Nasal Administration	p. 132
Pulmonary Administration	p. 132
Transdermal Administration	p. 133
Conclusions and Future Perspectives	p. 133
Manufacture Techniques of Chitosan-Based Microparticles and Nanoparticles for Biopharmaceuticals	p. 137
Introduction	p. 137
Water-in-Oil Emulsion and Chemical Cross-linking	p. 138
Drying Techniques	p. 141
Ionic Cross-linking Methods	p. 144
Coacervation and Precipitation Method	p. 151
Direct Interaction between Chitosan and Biopharmaceuticals	p. 152
Conclusions and Future Perspectives	p. 153
Chitosan and Derivatives for Biopharmaceutical Use: Mucoadhesive Properties	p. 159
Introduction	p. 159
Mucoadhesion	p. 160
Chitosan and Its Derivatives	p. 161
Biopharmaceutical Use of Chitosan and Its Derivatives	p. 171
Conclusions and Future Perspectives	p. 175
Chitosan-Based Systems for Mucosal Delivery of Biopharmaceuticals	p. 181
Introduction	p. 181
Important Challenges for the Delivery of Biopharmaceuticals by Mucosal Routes	p. 182
Interest in Chitosan for Mucosal Delivery of Biopharmaceuticals	p. 184
Chitosan-Based Delivery Nanosystems for Mucosal Delivery of Biopharmaceuticals	p. 188
Conclusions and Future Perspectives	p. 200
Chitosan-Based Delivery Systems for Mucosal Vaccination	p. 211
Introduction	p. 211
Adjuvant Properties of Chitosan	p. 212
Chitosan in the Delivery of Protein and Subunit Vaccines	p. 213
Chitosan-Based Formulations of DNAVaccines	p. 215
Vaccine Formulations Using Chitosan in Combination with Other Polymers	p. 216
Chitosan Derivatives in Vaccine Carrier Design	p. 217
Conclusions and Future Perspectives	p. 220
Chitosan-Based Nanoparticulates for Oral Delivery of Biopharmaceuticals	p. 225
Introduction	p. 225
Challenges on the Oral Delivery of Therapeutic Proteins	p. 226
Challenges on the Oral Delivery of Genetic Material	p. 227
Role of Chitosan in the Protection of Biopharmaceuticals in the Gastrointestinal Tract	p. 229
Chitosan-Based Nanoparticles for Oral Delivery of Therapeutic Proteins	p. 232
Chitosan-Based Nanoparticles for Oral Delivery of Genetic Material	p. 234
Conclusions and Future Perspectives	p. 236
Chitosan-Based Systems for Ocular Delivery of Biopharmaceuticals	p. 243
Introduction	p. 243
Ocular Delivery of Biopharmaceuticals	p. 244
Chitosan: A Suitable Biomaterial for Ocular Therapeutics	p. 244
Chitosan-Based Systems for Ocular Delivery of Biomacromolecules	p. 245
Toxicological and Compatibility Aspects of Chitosan-Based Ocular Systems	p. 249
Conclusions and Future Perspectives	p. 250
Chemical Modification of Chitosan for Delivery of DNA and siRNA5	p. 25
Introduction	p. 255
Hydrophilic Modification	p. 256
Hydrophobic Modification	p. 257
Specific Ligand Modification	p. 259
pH-Sensitive Modification	p. 264
Conclusions and Future Perspectives	p. 269
Advanced Application of Chitosan and Derivatives for Biopharmaceuticals	p. 275
Target-Specific Chitosan-Based Nanoparticle Systems for Nucleic Acid Delivery	p. 277
Introduction	p. 277
Chitosan-Based Nanoparticle Delivery Systems	p. 283
Illustrative Examples of DNAVaccine Delivery	p. 286
Illustrative Examples of Nucleic Acid Delivery Systems for Cancer Therapy	p. 288
Illustrative Examples of Nucleic Acid Delivery Systems for Anti-Inflammatory Therapy	p. 291
Conclusions and Future Perspectives	p. 294
Functional PEGylated Chitosan Systems for Biopharmaceuticals	p. 301
Introduction	p. 301
PEGylated Chitosan for the Delivery of Proteins and Peptides	p. 304
PEGylated Chitosan for Delivery of Nucleic Acids	p. 308
PEGylated Chitosan for Delivery of Other Macromolecular Biopharmaceuticals	p. 311
PEGylated Chitosan Used for Cellular Scaffolds	p. 313
Conclusions and Future Perspectives	p. 313
Stimuli-Sensitive Chitosan-Based Systems for Biopharmaceuticals	p. 319
Introduction	p. 319
pH-Sensitive Chitosan-Based Systems	p. 319
Thermosensitive Chitosan-Based Systems	p. 321
pH-Sensitive and Thermosensitive Chitosan-Based Systems	p. 323
pH- and Ionic-Sensitive Chitosan-Based Systems	p. 325
Photo-Sensitive Chitosan-Based Systems	p. 325
Electrical-Sensitive Chitosan-Based Systems	p. 326
Magnetic-Sensitive Chitosan-Based Systems	p. 326
Chemical Substance-Sensitive Chitosan-Based Systems	p. 327
Conclusions and Future Perspectives	p. 327
Chitosan Copolymers for Biopharmaceuticals	p. 333
Introduction	p. 333
Chitosan-g-Poly(Ethylene Glycol)	p. 337
Chitosan-g-Polyethylenimine	p. 347
Other Copolymers of Chitosan	p. 357
Copolymers of Chitosan with Promising Applications	p. 363
Conclusions and Future Perspectives	p. 368
Application of Chitosan for Anticancer Biopharmaceutical Delivery	p. 381
Introduction	p. 381
Chitosan and Cancer: Intrinsic Antitumor Activity of the Polymer Itself	p. 382
Chitosan Formulations Developed for Classic Anticancer Drugs	p. 383
Biopharmaceuticals Delivered by Chitosan Preparations	p. 384
Active Targeting Strategies and Multifunctional Chitosan Formulations	p. 388
Conclusions and Future Perspectives	p. 389
Chitosan-Based Biopharmaceutical Scaffolds in Tissue Engineering and Regenerative Medicine	p. 393
Introduction	p. 393
Fabrication of Chitosan-Based Biopharmaceuticals Scaffolds	p. 395
Applications of Chitosan-Based Biopharmaceutical Scaffolds in Tissue Engineering and Regenerative Medicine	p. 403
Future Trends: Regenerative Engineering	p. 416
Conclusions and Future Perspectives	p. 417
Wound-Healing Properties of Chitosan and Its Use in Wound Dressing Biopharmaceuticals	p. 429
Introduction	p. 429
Brief Review of Wound Repair	p. 430
Wound-Healing Effects of Chitosan	p. 433
Chitosan for Wound Therapeutics Delivery	p. 440
Conclusions and Future Perspectives	p. 444
Regulatory Status, Toxicological Issues, and Clinical Perspectives	p. 451
Toxicological Properties of Chitosan and Derivatives for Biopharmaceutical Applications	p. 453
Introduction	p. 453
In Vitro Toxicity of Chitosan and Derivatives	p. 454
In Vivo Toxicity of Chitosan and Derivatives	p. 457
Conclusions and Future Perspectives	p. 459
Regulatory Status of Chitosan and Derivatives	p. 463
Introduction	p. 463
Source	p. 464
Characterization	p. 464
Purity	p. 465
Applications of Advanced Uses of Chitosan	p. 466
Regulatory Considerations for Chitosan and Chitosan Derivatives in the European Union, and Medical Devices or Combination Products with Medical Device (CDRH) Lead	p. 468
Regulatory Pathways	p. 469
Chitosan Medical Products: US Regulatory Review Processes for Medical Devices or Combination Products with CDRH Lead	p. 469
Chitosan Wound Dressings	p. 470
The European Regulatory System: The European Medicines Agency (EMA) and European Directorate for the Quality of Medicines (EDQM)	p. 474
Further Regulatory Considerations	p. 475
Conclusions and Future Perspectives	p. 477
Disclaimer	p. 478
Patentability and Intellectual Property Issues Related to Chitosan-Based Biopharmaceutical Products	p. 483
Introduction	p. 483
Setting the Scene: The Role of Chitosan as a Pharmaceutical Excipient	p. 484
Addressing the Drivers for Scientific Progress on Chitosan: Innovation and Inventability	p. 495
Conclusions and Future Perspectives	p. 496
Quality Control and Good Manufacturing Practice (GMP) for Chitosan-Based Biopharmaceutical Products	p. 503
Introduction	p. 504
Regulatory Requirements for Production	p. 505
Manufacturing GMP: Fundamental Considerations	p. 508
Requirements for Rooms, Personnel, and Equipment	p. 511
Qualification and Validation	p. 511
Quality Control	p. 513
Monitoring and Maintenance of a GMP System	p. 519
Conclusions and Future Perspectives	p. 522
Preclinical and Clinical Use of Chitosan and Derivatives for Biopharmaceuticals: From Preclinical Research to the Bedside	p. 525
Introduction	p. 525
Chitosan as a Parenteral (Subcutaneous) Vaccine Platform	p. 526
Chitosan as an Immunotherapeutic Platform	p. 530
Conclusions and Future Perspectives	p. 537
References	p. 539
Index	p. 543
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