Hydrogels in Drug Delivery

Advances in the Manufacture, Characterization, and Application of Hydrogels to Address Current Global Healthcare Challenges

1st Edition - February 22, 2025
Imprint: Elsevier
Editors: Alejandro J. Paredes, Eneko Larrañeta, Garry Laverty, Ryan F. Donnelly
Language: English
Paperback ISBN:
9 7 8 - 0 - 4 4 3 - 2 2 0 1 7 - 3
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 2 2 0 1 8 - 0

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Hydrogels in Drug Delivery: Advances in the Manufacture, Characterization, and Application of Hydrogels to Address Current Global Healthcare Challenges presents the latest advances in hydrogels, ranging from their basic chemistry to specific application of existing and novel hydrogels in controlled drug delivery and biomedicine. Hydrogels have been increasingly used in the development of novel formulations in a wide variety of therapeutic and monitoring applications. Multidisciplinary work carried out by researchers working in synthetic chemistry, drug delivery, biomedicine and other fields has led to the development of novel polymers, enabling the preparation of hydrogels with adjustable physicochemical properties. Accordingly, these materials offer multiple advantages over other drug delivery systems, including an increased patient compliance by reducing the required number of medication doses, reducing the healing time in injuries, and simplifying patient monitoring by reducing the invasiveness of current methods.

Hydrogels in Drug Delivery is an essential resource for graduate students and researchers working within drug delivery and synthetic chemistry, biomedicine, material science, pharmacology, and chemical engineering.

Title of Book
Cover image
Title page
Table of Contents
Copyright
Contributors
Chapter 1. Synthesis and chemistry of hydrogels
1 Introduction
2 Cross-linking methods to prepare physical hydrogels
3 Three-dimensional (co)polymerization of monomers in the synthesis of hydrogels
4 Radiation-induced cross-linking of polymers in the synthesis of hydrogels
5 “Click chemistry” method for synthesis of hydrogels
6 Conclusion
Chapter 2. Characterization techniques of hydrogels in healthcare
1 Introduction
1.1 General considerations on the characterization of hydrogels
1.2 Characterization in hydrated and dried forms
1.2.1 Air-drying
1.2.2 Freeze-drying
2 Classification of characterization techniques for hydrogels
2.1 Characterization of the hydrogel composition
2.2 Characterization of the gelation process (sol-gel transition)
2.3 Characterization of the network type
2.4 Morphology
2.4.1 Microscopic techniques
2.4.2 Scattering techniques
2.4.3 Rheological characterization
2.4.4 Characterization of water content and distribution
3 Validation protocols for hydrogel fabrication
3.1 Sol-gel transition based fabrication
3.2 Flow-driven fabrication
3.3 Injectable hydrogels and extrusion based additive manufacturing
3.4 Printability criteria for additive manufacturing of hydrogels
4 Validation criteria for applications in healthcare
4.1 Toxicology
4.1.1 In vitro
4.1.2 In vivo
4.2 Drug delivery
4.2.1 In vitro degradation and cargo release
4.2.2 In vivo degradation and cargo release
4.3 Cell proliferation and differentiation
4.4 Tissue engineering
4.5 Final validation and clinical studies
5 Conclusions
Chapter 3. Molecularly imprinted hydrogels in drug delivery
1 Introduction
1.1 Imprinting within a hydrogel
1.2 Principles of using imprinted hydrogels for drug delivery
2 Examples of molecularly imprinted hydrogels for delivery
2.1 Temperature stimulation
2.2 pH stimulation
2.3 Light stimulation
2.4 Therapeutic applications
2.5 External delivery
2.6 Internal delivery
3 Perspective
Chapter 4. Peptide and protein-like hydrogels, synthesis, and applications in biomedicine
1 Background
2 Peptide and protein synthesis and manufacture
3 Peptides versus peptide-mimetics
4 Applications in healthcare
4.1 Hormone dysfunction and cancer
4.2 Long-acting injectables and sustained release systems
4.3 Antimicrobial, wound healing, and biomaterials
5 Conclusions and future perspectives
Chapter 5. Stimuli responsive hydrogels in drug delivery and biomedicine
1 Introduction
2 Temperature-responsive hydrogels
2.1 UCST-based hydrogels
2.2 LCST-based hydrogels
2.3 Biomedical applications of thermo-responsive hydrogels
3 pH-responsive hydrogels
3.1 Hydrogels based on pH-responsive acidic polymers
3.2 Hydrogels based on pH-responsive basic polymers
3.3 Applications of pH-responsive hydrogels
4 Ionic strength-responsive hydrogels
5 Ultrasounds-responsive hydrogels
5.1 US-responsive cross-links
5.2 Temperature-responsive hydrogels
5.3 Incorporation of perfluorocarbon
5.4 Other mechanisms
6 Magnetic-responsive hydrogels
6.1 Drug delivery
6.2 Hyperthermia therapy
6.3 Tissue engineering
7 Electric-responsive hydrogels
7.1 Conductive polymers
7.2 Conductive nanofillers and ionic liquids
8 Mechano-responsive hydrogels
8.1 Shear-responsive systems
8.2 Compression-responsive systems
8.3 Tension-responsive systems
9 Molecule-responsive hydrogels
9.1 Glucose-sensitive hydrogels
9.1.1 Glucose oxidase-loaded hydrogels
9.1.2 Hydrogels containing lectins
9.1.3 Hydrogels with phenylboronic acid moieties
9.2 Protein-responsive hydrogels
9.2.1 Enzyme-responsive hydrogels
9.2.2 Antigen-responsive hydrogels
9.3 Hydrogels responsive to other biomolecules
10 Light-responsive hydrogels
10.1 Photoisomerization
10.2 Photocleavage
10.3 Photoaddition
10.4 Photoexchange
11 Redox-responsive hydrogels
11.1 Redox-sensitive linkers
11.2 Linkers with redox conformational changes
11.3 Ferrocene-based hydrogels
11.4 Nanocomposite hydrogels
12 Future perspectives
Chapter 6. Hydrogel-forming microarray patches for drug delivery and diagnostic applications
1 Introduction
2 Materials for HF-MAPs
2.1 Synthetic polymers
2.1.1 Poly(methyl vinyl ether/maleic acid anhydride)
2.1.2 Poly(vinyl alcohol)
2.1.3 Gelatin methacryloyl
2.1.4 Natural polymers
3 Manufacturing method of HF-MAPs
4 Drug delivery for therapeutic applications
4.1 Transdermal delivery of low MW drugs
4.2 Transdermal delivery of biotherapeutics
5 Interstitial fluid sampling for diagnostic applications
6 Future outlook
7 Conclusion
Chapter 7. Injectable depot-forming hydrogels for long-acting drug delivery
1 Introduction
2 Polymers used to prepare injectable depot-forming hydrogels
2.1 Natural polymer-based hydrogels
2.1.1 Alginates
2.1.2 Chitosan
2.1.3 Gellan gum
2.1.4 Hyaluronic acid
2.1.5 Xyloglucan
2.1.6 Cyclodextrin
2.2 Synthetic polymer-based hydrogels
2.2.1 Poly(N-isopropyl acrylamide)
2.2.2 Poloxamer
2.2.3 Poly(ethylene glycol)-based hydrogels
2.2.4 Poly(ethylene glycol) diacrylate
3 Applications of injectable depot-forming hydrogels
3.1 Pain management
3.2 Cancer
3.3 Wound healing
3.4 Rheumatoid arthritis
3.5 Diabetes
3.6 Infectious diseases
3.7 Ocular diseases
4 Conclusions and future perspective
Chapter 8. Hydrogels for vaginal drug delivery and other applications
1 Introduction
2 Definition, formulation, and properties
2.1 Composition
2.2 Manufacturing
2.3 Vaginal applicators
2.4 Pharmaceutical characterization
2.5 Biological characterization
3 Healthcare applications
3.1 Medicated hydrogels
3.2 Nonmedicated hydrogels
4 Acceptability and preferences
5 Conclusions
Chapter 9. In situ gel forming formulations for topical drug delivery
1 Introduction
2 Classification of in situ gel
2.1 Thermosensitive
2.2 Ion sensitive
2.3 pH sensitive
2.3.1 Natural pH sensitive polymers
2.3.2 Synthesis methods for pH sensitive polymers
3 Application of transdermal in situ gels
3.1 Skin delivery
3.2 Nasal delivery
3.3 Ocular delivery
3.4 Rectal delivery
3.5 Vaginal delivery
3.5.1 Expert opinion
4 Conclusion
Chapter 10. The use of hydrogels in oral drug delivery
1 Introduction
2 Classification
2.1 Polymer origin
2.2 Crosslinking type
2.2.1 Physically crosslinked hydrogels
2.2.2 Chemically crosslinked hydrogels
2.3 Degradability
2.4 Size of the hydrogel
2.5 Sensitivity to external stimuli
2.6 Electrical charge of hydrogels
2.7 Polymeric composition
3 Characteristics of hydrogels
3.1 Swelling
3.2 Mucoadhesivity
3.3 Drug delivery
3.3.1 Controlled release systems by diffusion: reservoir- and matrix-based
3.3.2 Controlled release systems by swelling
3.3.3 Chemically controlled release systems
4 Applications of hydrogels in oral drug administration
4.1 Oral cavity administration
4.2 Site-specific oral administration
4.2.1 Gastric drug delivery
4.2.2 Intestine drug delivery
4.2.3 Colonic drug delivery
4.2.4 Peptides’ and proteins’ oral drug delivery
5 Conclusion
Chapter 11. 3D printed hydrogels: A promising material for biomedical applications
1 Introduction
2 Requirements for printable hydrogels
3 3D printing techniques for hydrogels
3.1 Inkjet-based 3D printing
3.2 Extrusion-based 3D printing
3.3 Laser printing
3.3.1 Stereolithography (SLA)
3.3.2 Two-photon polymerization
3.4 Digital light processing 3D printing
4 Hydrogels
4.1 Natural Hydrogels
4.1.1 Polysaccharide hydrogels
4.1.2 Glycosaminoglycan hydrogels
4.1.3 Polypeptide/protein hydrogels
4.2 Synthetic hydrogels
4.2.1 Polyacrylate hydrogels
4.2.2 Poly(ethylene glycol) hydrogels
4.2.3 Polyvinyl alcohol hydrogels
5 Emerging biomedical applications
5.1 Tissue engineering and regenerative medicine
5.1.1 Bone regeneration
5.1.2 Cartilage regeneration
5.1.3 Skin regeneration
5.1.4 Spinal cord regeneration
5.1.5 Skeletal muscle regeneration
5.1.6 Ovary regeneration
5.2 Surgical preparation
5.3 Soft robotics
5.4 Printable electronics
5.5 In vitro tissue modeling
6 Conclusions
Chapter 12. Hydrogels and their application in tissue regeneration
1 Introduction
1.1 History of hydrogels
1.2 Classification of hydrogels
2 Polymers used for hydrogel-based scaffolds
2.1 Natural-based hydrogels
2.1.1 Chitosan
2.1.2 Alginate
2.1.3 Proteins
2.2 Synthetic-based hydrogels
3 Requirements of hydrogels-based scaffolds in tissue engineering
4 Techniques for hydrogel-based scaffolds manufacturing
4.1 Emulsification and lyophilization
4.2 Solvent casting/particle leaching
4.3 Gas foaming technique
4.4 Electrospinning process
4.5 3D bioprinting
5 Application of hydrogels in tissue engineering
5.1 Cardiac tissue
5.2 Bone tissue
5.3 Cartilage tissue
5.4 Nervous tissue
5.5 Other tissue engineering applications
6 Conclusions
Chapter 13. The role of hydrogels in wound healing
1 Introduction
2 Wound healing process
3 Hydrogels as advanced wound dressings
4 Hydrogel cross-linking methods
4.1 Physical cross-linking
4.1.1 Hydrogen bonding
4.1.2 Ionic bonding
4.1.3 Hydrophobic interactions
4.1.4 Crystallization
4.2 Chemical cross-linking
4.2.1 Schiff base reaction
4.2.2 Michael addition reaction
4.2.3 Free radical polymerization
4.2.4 “Click” chemistry
4.3 Enzymatic cross-linking
5 Stimuli-responsive hydrogels
6 Commercially available hydrogel dressings for chronic wounds
7 Practical concerns limiting the translation into the clinic of advance wound dressings
8 Conclusions and future perspectives
Index

Alejandro J. Paredes

Dr Alejandro J. Paredes is a Pharmacist by training (2011) and holds a PhD (2016), both degrees from the National University of Córdoba, Argentina. Dr Paredes made pre- and post-doctoral visits to laboratories in Cuba, Uruguay, Spain, and Italy, and worked as a Research Fellow at Queen’s University Belfast (QUB, UK). In January 2021, Dr Paredes took up a Lectureship (Assistant Professor) at QUB and was promoted to Senior Lecturer (Associate Professor) in April 2023. At QUB, he leads a group focused on controlled and targeted drug delivery using nanocrystals. He obtained a PGCHET in 2022 and teaches Pharmaceutical Sciences in multiple modules for the BSc, MPharm, and MSc programs at QUB. Alejandro is a named inventor in two patents and has authored >140 publications, including 54 research papers, 10 review articles, 2 book chapters, 2 textbooks, and >70 conference presentations. Dr Paredes has obtained >£3.4M of funding for his research, with prestigious grants as PI from EPSRC, the Academy of Medical Sciences, the Royal Society, and Applied Microbiology International. Dr Paredes obtained the Emerging Scientist Award 2024 from the Academy of Pharmaceutical Sciences (APS, UK) and is a Fellow of the Higher Education Academy (UK) and CICOPS (Italy). Alejandro is an active member of the APS, Controlled Release Society, American Association of Pharmaceutical Scientists, Applied Microbiology International, and British Society for Nanomedicine. Moreover, he is a member of the Early Career Editorial Board of Materials Today Bio, the Advisory Board of AAPS PharmSciTech and an Associate Editor of Drug Delivery and Translational Research.

Affiliations and expertise

School of Pharmacy, Queen’s University Belfast, Belfast, Northern Ireland

Eneko Larrañeta

Prof. Eneko Larrañeta holds the Chair in Pharmaceutical Materials Science at the School of Pharmacy, Queen's University Belfast, specialising in drug delivery systems and biomaterials. He earned a BSc in Chemistry and a PhD in Physical Chemistry from the University of Navarra, where his research centred on self-assembled hydrogels. After completing his PhD in 2012, Prof. Larrañeta worked as a research fellow in nanotechnology for drug delivery before joining Queen's University Belfast in 2013 to advance microneedle technology for transdermal drug delivery. His expertise spans hydrogels, nano/microparticles, and microneedle-based systems. Currently, his research focuses on implantable systems for sustained drug release, utilising techniques like melt processing and additive manufacturing. He has published over 100 peer-reviewed papers, edited multiple books, and contributed numerous book chapters. Prof. Larrañeta has secured funding from leading organisations and collaborated widely with pharmaceutical and cosmetics companies. He has been named a Clarivate Highly Cited Researcher and recognised among the top 2% of scientists in his field by Stanford University’s analysis using Scopus data. He is a Fellow of the UK Higher Education Academy and a member of the Royal Society of Chemistry and the Society for Applied Microbiology.

Affiliations and expertise

School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, Northern Ireland

Garry Laverty

Dr Garry Laverty is a Senior Lecturer at the School of Pharmacy Queen's University Belfast. His Biofunctional Nanomaterials group develop self-assembling hydrogel platforms for biomedical applications based on peptide and their unnatural variants (peptide-mimetics). These have huge potential within the fields of drug delivery and biomaterials, with the group's focus primarily on the development of sustained release systems (in situ forming injectable hydrogel depots) primarily for use in HIV/AIDs prevention combined with contraception. This system is also showing promise for use in conditions with medication adherence and drug delivery issues e.g. ocular use, cancer, tuberculosis, malaria, antipsychotics. Garry's work is funded by £1.5 million of competitive research funding from sources including: the Engineering and Physical Sciences Research Council (EPSRC), the Medical Research Council (MRC), the Wellcome Trust, the Royal Society, Innovate UK and Invest NI. He has authored 53 publications relating to peptide materials and drug delivery. He also holds an interest in the application of neutron scattering techniques to define the microscopic properties of hydrogels, having been awarded substantial beam time by Institut Laue-Langevin (ILL, Grenoble) and UKRI Science Technology Facilities Council ISIS Neutron and Muon Source facilities.

Affiliations and expertise

School of Pharmacy, Queen’s University Belfast, Belfast, Northern Ireland

Ryan F. Donnelly

Professor Ryan Donnelly holds the Chair in Pharmaceutical Technology at the School of Pharmacy, Queen’s University Belfast, where he is Director of Research. A registered pharmacist, his research is centred on design and characterisation of advanced polymeric drug delivery systems for transdermal and intradermal drug delivery, with a strong emphasis on improving patient outcomes. He is currently developing a range of novel microneedle technologies through independent research, but also in collaboration with several major pharmaceutical companies. His work has attracted more than £30 million in funding and he has authored over 1000 peer-reviewed publications, including 11 patent applications, 7 textbooks, 28 book chapters and approximately 360 full papers. He leads a personal research group of approximately 50 people from 15 different countries and has been an invited speaker at numerous national and international conferences. Professor Donnelly is Europe/Africa Editor of Drug Delivery & Translational Research. He has won the International Association for Pharmaceutical Technology (APV) Research Award for Outstanding Achievements in the Pharmaceutical Sciences (2024), the Royal Pharmaceutical Society’s Harrison Medal (2024), the Kydonieus Foundation Transdermal Delivery Award (2024), the European Journal of Pharmaceutics & Biopharmaceutics Most Cited Paper Award (2023), the Drug Delivery & Translational Research Best Paper Award (2023), Visit Belfast’s Ambassador Award for Life & Health Sciences (2022), the Academy of Pharmaceutical Sciences Innovative Science Award (2020), Evonik’s Resomer Award (2018), the Controlled Release Society’s Young Investigator Award (2016), BBSRC Innovator of the Year (2013), the American Association of Pharmaceutical Scientists Pharmaceutical Research Meritorious Manuscript Award (2013 & 2022), the GSK Emerging Scientist Award (2012), the Royal Pharmaceutical Society’s Science Award (2011) and the Pharmaceutical Society of Northern Ireland’s Gold Medal (1999).

Affiliations and expertise

School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast , Northern Ireland

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Hydrogels in Drug Delivery

Advances in the Manufacture, Characterization, and Application of Hydrogels to Address Current Global Healthcare Challenges

Purchase options

World Book Day Celebration!

Institutional subscription on ScienceDirect

Alejandro J. Paredes

Eneko Larrañeta

Garry Laverty

Ryan F. Donnelly

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