Read more
This research book covers the major aspects relating to the use of novel delivery systems in enhancing both transdermal and intradermal drug delivery. It provides a review of transdermal and intradermal drug delivery, including the history of the field and the various methods employed to produce delivery systems from different materials such as device design, construction and evaluation, so as to provide a sound background to the use of novel systems in enhanced delivery applications.
Furthermore, it presents in-depth analyses of recent developments in this exponentially growing field, with a focus on microneedle arrays, needle-free injections, nanoparticulate systems and peptide-carrier-type systems. It also covers conventional physical enhancement strategies, such as tape-stripping, sonophoresis, iontophoresis, electroporation and thermal/suction/laser ablation Discussions about the penetration of the stratum corneum by the various novel strategies highlight the importance of the application method. Comprehensive and critical reviews of transdermal and intradermal delivery research using such systems focus on the outcomes of in vivoanimal and human studies. The book includes laboratory, clinical and commercial case studies featuring safety and patient acceptability studies carried out to date, and depicts a growing area for use of these novel systems is in intradermal vaccine delivery. The final chapters review recent patents in this field and describe the work ongoing in industry.
List of contents
About the Editors xiii
Contributors xv
Advances in Pharmaceutical Technology: Series Preface xvii
Preface xix
1 Introduction 1
Gary P.J. Moss
1.1 The Subcutis (Subcutaneous Fat Layer) 1
1.2 The Dermis 2
1.3 Skin Appendages 2
1.4 The Subcutaneous Sensory Mechanism 3
1.5 The Epidermis 5
1.6 The stratum germinativum 5
1.7 The stratum spinosum 5
1.8 The stratum granulosum 6
1.9 The stratum lucidum 6
1.10 The stratum corneum 6
1.10.1 Routes of Absorption 9
1.10.2 Transdermal Permeation - Mechanisms of Absorption 9
1.11 Theoretical Considerations 11
1.12 Physicochemical Properties of the Penetrant 13
1.12.1 Partition Coefficient 13
1.12.2 Molecular Size and Shape 14
1.12.3 Applied Concentration/Dose 15
1.12.4 Solubility and Melting Point 15
1.12.5 Ionisation 15
1.12.6 Physiological Factors Affecting Percutaneous Absorption 16
1.13 Physiological Properties of the Skin 16
1.13.1 Skin Condition 16
1.13.2 Skin Hydration and Occlusion 17
1.13.3 Skin Age 17
1.13.4 Regional Variation (Body Site) 18
1.13.5 Race 19
1.13.6 Skin Temperature 19
1.14 Vehicle Effects 19
1.15 Modulation and Enhancement of Topical and Transdermal Drug Delivery 20
1.15.1 Chemical Modulation of Permeation 21
1.15.2 Physical Methods of Enhancement 26
2 Application of Spectroscopic Techniques to Interrogate Skin 41
Jonathan Hadgraft, Rita Mateus and Majella E. Lane
2.1 Introduction 41
2.2 Vibrational Spectroscopic Methods 42
2.3 Electronic Spectroscopic Methods 46
2.3.1 UV and Fluorescence 46
2.3.2 Nuclear Magnetic Resonance 47
2.4 Miscellaneous Spectroscopic Methods 48
2.4.1 Opto?]Thermal Transient Emission Radiometry 48
2.4.2 Electron Spin Resonance 48
2.4.3 Impedance Spectroscopy 49
2.4.4 Laser?]Induced Breakdown Spectroscopy 49
2.4.5 Photoacoustic Spectroscopy 50
2.4.6 Mass Spectrometry Imaging 50
2.5 Conclusions and Future 50
3 Analysis of the Native Structure of the Skin Barrier by Cryo?]TEM Combined with EM?]Simulation 57
Lars Norlén
3.1 Introduction 57
3.2 Our Approach: In Situ Biomolecular Structure Determination in Near?]Native Skin 58
3.2.1 Step 1: Cryo?]Electron Microscopy of Vitreous Sections 60
3.2.2 Steps 2-3: Molecular Model Building and Electron Microscopy Simulation 66
3.2.3 Step 4: Confrontation of Observed Data with Simulated Data 66
3.3 Molecular Organisation of the Horny Layer's Fat Matrix 67
3.4 Molecular Organisation of the Horny Layer's Keratin Filament Matrix 67
3.5 Final Remark 68
4 Intradermal Vaccination 71
Marija Zaric and Adrien Kissenpfennig
4.1 Vaccination 71
4.1.1 Disadvantages Associated with Conventional Vaccination 72
4.2 Dendritic Cells Immunobiology 73
4.3 Skin Anatomy and Physiology 74
4.3.1 The Role of Skin in Vaccine Delivery 75
4.4 The Skin Dendritic Cell Network 76
4.4.1 Langerhans Cells and the 'Langerhans Cell Paradigm' 76
4.4.2 Dermal Dendritic Cell Network 77
4.4.3 Dendritic Cell Subsets in the Skin?]Draining Lymph Node 79
4.4.4 Human Dendritic Cells in the Skin 80
4.4.5 The Role of Skin Dendritic Cells Subsets in Transdermal Immunisation 81
4.5 The DTR?]DT Depletion System 82
4.5.1 Langerin?
About the author
Dr Ryan Donnelly is Reader in Pharmaceutics at Queen's University Belfast. Dr Donnelly's research is centred on design and physicochemical characterisation of advanced polymeric drug delivery systems for transdermal and topical drug delivery, with a strong emphasis on improving therapeutic outcomes for patients. He is also a technical director at Swedish Pharma AB. Still at a relatively early stage of his career, he has authored over 300 peer-reviewed publications, including 3 patent applications, 3 textbooks, 16 book chapters and approximately 100 full papers. He's the holder of many awards including the current GSK Emerging Scientist Award.
Dr Raj Thakur is Lecturer in Pharmaceutics at Queen's University Belfast. He obtained his PhD in polymer science in 2009 from Queens University Belfast and his MSc in drug delivery in 2006 from University Science Malaysia. He has a BSc in Pharmacy from Jawaharlal Nehru Technological University, India. Dr Thakur's research interests are in development and evaluation of novel
in situ forming controlled release implants and ocular and transdermal drug delivery using novel minimally-invasive devices. He has published a textbook and over 30 scientific papers.
Summary
This research book covers the major aspects relating to the use of novel delivery systems in enhancing both transdermal and intradermal drug delivery.
