by Zhao Li. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 148-158). / ACKNOWLEDGMENTS --- p.I / ABSTRACT --- p.II / LIST OF FIGURES --- p.VIII / LIST OF TABLES --- p.X / LIST OF PHOTOGRAPHS --- p.XI / LIST OF EQUIPMENTS --- p.XII / LIST OF APPENDICES --- p.XII / ABBREVIATIONS --- p.XIII / Chapter Chapter 1. --- Introduction and Literature Review --- p.1 / Chapter I. --- Introduction --- p.1 / Chapter II. --- Literature Review --- p.6 / Chapter 1.1. --- Foreword --- p.6 / Chapter 1.2. --- Advantages of iontophoresis --- p.7 / Chapter 1.3. --- Historical background --- p.7 / Chapter 1.4. --- Definitions --- p.9 / Chapter 1.5. --- Principles of ionic transport in an electric field --- p.10 / Chapter 1.6. --- Theory and mechanism of iontophoretic delivery --- p.12 / Chapter 1.7. --- Development of iontophoretic devices --- p.13 / Chapter 1.8. --- Process of transdermal drug delivery --- p.14 / Chapter 1.9. --- Clinical application of iontophoresis --- p.14 / Chapter 1.10. --- Present problems of iontophoretic devices --- p.16 / Chapter 1.11. --- Effects of physiochemical factors on iontophoretic delivery --- p.20 / Chapter 1.11.1. --- pH --- p.20 / Chapter 1.11.2. --- Ionic strength --- p.21 / Chapter 1.11.3. --- Buffer solution --- p.21 / Chapter 1.11.4. --- Electrode --- p.22 / Chapter 1.11.5. --- Concentration and temperature --- p.22 / Chapter 1.11.6. --- Molecular weight --- p.22 / Chapter 1.11.7. --- Blood supply --- p.23 / Chapter 1.11.8. --- Pharmaceutical additives --- p.23 / Chapter 1.11.9. --- Four-electrodes system --- p.24 / Chapter 1.11.10. --- Skin properties --- p.24 / Chapter 1.12. --- Future prospect --- p.25 / Chapter Chanter 2. --- Design of PSPDC iontophoretic device / Chapter 2.1. --- Introduction --- p.29 / Chapter 2.2. --- Materials and Methods --- p.30 / Chapter 2.2.1. --- Principle of the new iontophoretic device --- p.30 / Chapter 2.2.2. --- Mechanism of pulsed short-circuit system --- p.32 / Chapter 2.2.3. --- Structure of self-made PSPDC device --- p.34 / Chapter 2.2.4. --- Safety system of the PSPDC device --- p.35 / Chapter 2.2.5. --- Test of the electrical properties of PSPDC device --- p.36 / Chapter 2.3. --- Results --- p.41 / Chapter 2.3.1. --- Efficacy of pulsed short-circuit system --- p.41 / Chapter 2.3.2. --- "Output characteristics of PDC, DC and PSPDC fields" --- p.42 / Chapter 2.3.3. --- Impact energy and depolarization action of PDC and PSPDC fields --- p.47 / Chapter 2.4. --- Discussion and Summary --- p.52 / Chapter 2.4.1. --- Discussion --- p.52 / Chapter 2.4.2. --- Summary --- p.53 / Chapter 2.5. --- Photochrome and Appendix --- p.56 / Chapter Chapter 3. --- Iontophoretic Experiment / Chapter 3.1. --- Introduction --- p.65 / Chapter 3.2. --- Materials and Methods --- p.67 / Materials --- p.67 / Methods --- p.68 / Chapter 3.2.1. --- Permeation experiments of different electric fields-an in vitro study --- p.69 / Chapter 3.2.2. --- Comparison of efficiency between DC and PSPDC-excised skin --- p.70 / Chapter 3.2.3. --- Comparison of permeation efficiency between DC and PSPDC- pedicled skin flap --- p.71 / Chapter 3.2.4. --- In vivo permeation experiment in the rat --- p.72 / Chapter 3.2.5. --- In vivo permeation experiment with the radioisotope labelled molecules --- p.73 / Chapter 3.2.6. --- Clinical observations of PSPDC iontophoresis device --- p.74 / Chapter 3.2.7. --- Experiments on the alteration and recovery of skin impedance under prolonged iontophoresis --- p.75 / Chapter 3.2.8. --- Skin damage by iontophoresis --- p.76 / Chapter 3.3. --- Results: --- p.77 / Chapter 3.3.1. --- Permeation rates of different electric fields (in vitro: excised rat skin) --- p.77 / Chapter 3.3.2. --- Comparison between DC and PSPDC-- excised rat skin --- p.78 / Chapter 3.3.3. --- Comparison between DC and PSPDC-- pedicled skin --- p.79 / Chapter 3.3.4. --- In vivo permeation experiment in the rat --- p.80 / Chapter 3.3.5. --- In vivo permeation experiment with radioisotope labelled molecules --- p.81 / Chapter 3.3.6. --- Alteration and recovers of skin impedance under prolonged iontophoresis --- p.88 / Chapter 3.3.7. --- Observing skin damage by iontophoresis --- p.89 / Chapter 3.3.8. --- Clinical observation of PSPDC iontophoresis device --- p.90 / Chapter 3.4. --- Discussion and summary --- p.91 / Chapter 3.4.1. --- Discussion --- p.91 / Chapter 3.4.2. --- Summary --- p.96 / Chapter 3.5. --- Photochrome and Appendix --- p.97 / Chapter Chapter 4. --- Electrical properties of scar skin and normal skin / Chapter 4.1. --- Introduction --- p.104 / Chapter 4.2. --- Material and method --- p.106 / Chapter 4.2.1. --- Principle of four point measurement method --- p.106 / Chapter 4.2.2. --- Measurement of electrical impedance of scar and skin with four point method --- p.107 / Chapter 4.2.3. --- Principle of three point measurement method --- p.108 / Chapter 4.2.4. --- Measurement of impedance of scar and skin with three point method --- p.110 / Chapter 4.2.5. --- Imitation equivalent circuit of normal skin with two point method --- p.111 / Chapter 4.3. --- Results --- p.113 / Chapter 4.3.1. --- Impedance of scar tissue and skin tissue with four point method --- p.113 / Chapter 4.3.2. --- Measurement of impedance of scar tissue and skin with three point method --- p.117 / Chapter 4.3.3. --- "Relationship of resistance, reactance, impedance and frequency" --- p.123 / Chapter 4.3.4. --- Imitation equivalence circuit of normal skin with point method --- p.124 / Chapter 4.4. --- Discussion and Summary --- p.125 / Chapter 4.4.1. --- Discussion --- p.125 / Chapter 4.4.2. --- Summary --- p.131 / Chapter 4.5. --- Photochrome and Appendix --- p.132 / Chapter Chapter 5. --- General discussion and conclusion / Chapter 5.1. --- General discussion --- p.137 / Chapter 5.2. --- Conclusion --- p.143 / References I --- p.148 / References II --- p.158 / LIST OF FIGURES / Fig. 2. 1. Imitating waveform of 1:1PDC and 12:1 PSPDC fields --- p.32 / Fig. 2. 2. The circuit of Pulsed short-circuit in PSPDC system --- p.32 / Fig. 2. 3. Block diagram of PSPDC system --- p.35 / Fig. 2. 4. Scheme of measuring short-circuit action of PSPDC apparatus --- p.36 / Fig. 2. 5. Measurement of EP of several electric fields --- p.37 / Fig. 2. 6. Measurement of impact energy and depolarization action --- p.39 / Fig. 2. 7. The distribution of permeating current and releasing current --- p.41 / Fig. 2. 8. Comparing the polarization degree of different electric fields --- p.42 / Fig. 2. 9. Comparing alternating current component of electric fields --- p.43

by Lui Kong Kei, Walter. / Thesis submitted in: July 1999. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 115-122). / Abstracts in English and Chinese. / ABSTRACT --- p.i / 摘要 --- p.iv / ACKNOWLEDAGE --- p.vi / LIST OF FIGURES --- p.xi / LIST OF TABLES --- p.xiii / LIST OF APPENDIX --- p.xiii / ABBREVATIONS --- p.xiv / Chapter CHAPTER ONE: --- INTRODUCRION --- p.2 / Chapter 1.1 --- DEFINITION --- p.2 / Chapter 1.2 --- HISTORICAL BACKGROUND --- p.2 / Chapter 1.3 --- ADVANTAGES AND CLINICAL APPLICATION OF IONTOPHORESIS --- p.5 / Chapter 1.3.1 --- ADVANTAGES OF IONTOPHORESIS --- p.6 / Chapter 1.3.2 --- CLINICAL APPLICATION OF IONTOPHORESIS --- p.7 / Chapter 1.4 --- STRUCTURE AND ELECTRICAL PROPERTIES OF SKIN --- p.7 / Chapter 1.4.1 --- SKIN STRUCTURE --- p.8 / Chapter 1.4.2 --- SKIN PERMSELECTIVITY --- p.9 / Chapter 1.4.3 --- ELECTRICAL PROPERTIES OF SKIN --- p.9 / Chapter 1.5 --- PRINCIPLES OF IONIC TRANSPORT IN AN ELECTRIC FIELD --- p.10 / Chapter 1.6 --- THEORETICAL BASIS --- p.12 / Chapter 1.6.1 --- NERNST-PLANCK THEORY OF DRUG DELIVERY BY IONTOPHORESIS --- p.12 / Chapter 1.6.2 --- CONVECTIVE FLOW --- p.14 / Chapter 1.6.3 --- THEORETICAL TREATMENT OF CONVECTIVE FLOW --- p.15 / Chapter 1.6.4 --- THE ENHANCEMENT RATIO (ER) --- p.16 / Chapter 1.6.5 --- ALTERATIONS IN THE PERMEABILITY OF SKIN AND DAMAGE FACTOR (DF) --- p.16 / Chapter 1.7 --- PATHWAYS FOR TRANSPORT --- p.17 / Chapter 1.8 --- FACTORS AFFECTING IONTOPHORETIC DELIVERY --- p.19 / Chapter 1.8.1 --- ELECTIC CURRENT --- p.19 / Chapter 1.8.1.1 --- CURRENT DENSITY --- p.20 / Chapter 1.8.1.2 --- CURRENT MODES --- p.21 / Chapter 1.8.1.2.1 --- Direct Current (DC) --- p.21 / Chapter 1.8.1.2.2 --- Pulsed Direct Current (PDC) --- p.21 / Chapter 1.8.1.2.3 --- Comparing Direct Current (DC) with Pulsed Direct Current (PDC) --- p.23 / Chapter 1.8.1.2.4 --- Pulsed Short-circuit Pulsed Direct Current (PSPDC) --- p.24 / Chapter 1.8.2 --- PHYSIOCHEMICAL PROPERTIES OF THE PERMEANT --- p.26 / Chapter 1.8.3 --- ELECTROLYTE COMPOSITION --- p.28 / Chapter 1.8.4 --- BIOLOGICAL FACTORS --- p.30 / Chapter 1.9 --- IN-VITRO EXPERIMENT DESIGN --- p.30 / Chapter 1.9.1 --- SKIN AND SYNTHETIC MEMBRANE IN IONTOPHORETIC RESEARCH --- p.30 / Chapter 1.9.2 --- DIFFUSION CELL --- p.32 / Chapter 1.9.3 --- ELECTRODES --- p.33 / Chapter 1.10 --- THE PURPOSE OF PRESENT STUDY --- p.34 / Chapter CHAPTER TWO: --- MATERIALS AND METHODS --- p.35 / Chapter 2.1 --- MATERIAL --- p.35 / Chapter 2.1.1 --- ANIMAL MODEL --- p.35 / Chapter 2.1.2 --- APPARATUS AND INSTRUMENTS --- p.35 / Chapter 2.1.3 --- REAGENTS --- p.37 / Chapter 2.2 --- METHODS --- p.38 / Chapter 2.2.1 --- PREPARATION OF THE SIDE-BI-SIDE DIFFUSION CELL --- p.38 / Chapter 2.2.1.1 --- MEMBRANE PREPARATION FOR SKIN PERMEABILITY STUDIES --- p.38 / Chapter 2.2.1.2 --- MOUNTING THE TISSUE MEMBRANE IN SIDE-BI-SIDE DIFFUSION CELL --- p.39 / Chapter 2.2.1.3 --- STABILIZING THE TISSUE MEMBRANE AND TESTING FOR THE TIGNTNESS --- p.40 / Chapter 2.2.1.4 --- SILIVER/SILVER CHORIDE ELECTRODE (Ag/AgCl) --- p.41 / Chapter 2.2.2 --- IN-VITRO IONTOPHORETIC PERMEATION EXPERIMENT --- p.42 / Chapter 2.2.2.1 --- IONTOPHORETIC PERMEATION KINETICS OF MANNITOL --- p.42 / Chapter 2.2.2.1.1 --- Reagents --- p.42 / Chapter 2.2.2.1.2 --- In-vitro experiment process --- p.43 / Chapter 2.2.2.1.3 --- Testing parameters --- p.43 / Chapter 2.2.2.1.4 --- Sampling and assay --- p.44 / Chapter 2.2.2.1.5 --- Data analysis --- p.44 / Chapter 2.2.2.2 --- IONTOPHORETIC PERMEATION KINETICS OF ANGIOTENSIN II --- p.46 / Chapter 2.2.2.2.1 --- Reagents --- p.46 / Chapter 2.2.2.2.2 --- In-vitro experiment process and testing parameters --- p.47 / Chapter 2.2.2.2.3 --- Sampling and assay --- p.47 / Chapter 2.2.2.2.4 --- Data analysis --- p.47 / Chapter 2.2.3 --- IMPEDANCE MEASUREMENT OF EXCISED SKIN --- p.48 / Chapter 2.2.4 --- INFLUENCE OF IONTOPHORESIS ON THE IMPEDANCE OF EXCISED FULL-THICKNESS NUDE MOUSE SKIN --- p.50 / Chapter 2.2.4.1 --- Experiment process --- p.50 / Chapter 2.2.4.2 --- Measurement and data analysis --- p.51 / Chapter 2.2.5 --- PASSIVE SOLUTE TRANSPORT EXPERIMENT --- p.52 / Chapter 2.2.5.1 --- PASSIVE TRANSPORT OF TRITIATED WATER --- p.52 / Chapter 2.2.5.1.1 --- Reagents --- p.53 / Chapter 2.2.5.1.2 --- Experimental process --- p.53 / Chapter 2.2.5.1.3 --- Assay and data analysis --- p.55 / Chapter 2.2.5.2 --- PASSIVE TRANSPORT OF MANNITOL --- p.55 / Chapter 2.2.5.2.1 --- Reagents --- p.56 / Chapter 2.2.5.2.2 --- Experimental process --- p.56 / Chapter 2.2.5.2.3 --- Assay and data analysis --- p.58 / Chapter 2.2.6 --- STATISTIC METHODS USED FOR ANALYSIS --- p.59 / Chapter CHAPTER THREE: --- RESULTS --- p.60 / Chapter 3.1 --- RESULTS OF IN-VITRO IONTOPHORETIC PERMEATION EXPERIMENTS --- p.60 / Chapter 3.1.1 --- IONTOPHORETIC PERMEATION KINETICS OF MANNITOL --- p.60 / Chapter 3.1.2 --- IONTOPHORETIC PERMEATION KINETICS OF ANGIOTENSIN II --- p.69 / Chapter 3.2 --- RESULTS OF EFFECT OF IONTOPHORESIS ON THE IMPEDANCE OF THE EXCISED FULL-THICKNESS NUDE MOUSE SKIN --- p.78 / Chapter 3.3 --- SOLUTE TRANSPORT EXPERIMENTS --- p.81 / Chapter 3.3.1 --- WATER TRANSPORT EXPERIMENT --- p.81 / Chapter 3.3.2 --- MANNITOL TRANSPORT EXPERIMENT --- p.86 / Chapter CHAPTER FOUR: --- DISCUSSION --- p.93 / Chapter 4.1 --- ANIMAL MODEL --- p.93 / Chapter 4.2 --- EXPERIMENTAL CONDITION OF DIFFUSION PERMEATION CELL --- p.94 / Chapter 4.3 --- IN- VITRO PERMEATION EXPERIMENTS --- p.95 / Chapter 4.3.1 --- MANNITOL --- p.95 / Chapter 4.3.2 --- ANGIOTENSIN II --- p.95 / Chapter 4.3.3 --- RESULTS OF IONTOPHORETIC PERMEATION STUDIES --- p.97 / Chapter 4.4 --- INFLUENCE OF IONTOPHORESIS ON THE SKIN IMPEDANCE --- p.99 / Chapter 4.5 --- SOLUTE TRANSPORT EXPERIMENT --- p.102 / Chapter 4.6 --- FUTURE PROSPECTS --- p.106 / Chapter CHAPTER FIVE: --- CONCLUSION --- p.107 / APPENDIX ONE --- p.108 / APPENDIX TWO --- p.109 / REFERENCE --- p.115

Thesis (M.S.)--University of Michigan, 1979.

Thesis (M.S.)--University of Michigan, 1979.

Thesis (Master)--İzmir Institute of Technology, İzmir, 2005. / Keywords: Iontophoresis, Hyaluronic acid Includes bibliographical references (leaves. 94-105).

A sublingual electronic pill is a novel device designed to enhance delivery of drugs/biologics sublingually utilizing low-current electrical stimulation. Our primary aim was to explore safe limits of oral electrical stimulus in animals and conduct a randomized, sham-controlled animal study to quantify benefits of electrical stimulation on sublingual absorption of octreotide (a small peptide) as a first step in the development of this technology. A system to deliver low-current alternating and direct current stimuli to the oral mucosa of rabbits was constructed, and five groups were studied to determine the significance of sublingual octreotide diffusion in the presence of three different electrical stimulation scenarios: +DC (+4 mA), -DC (-4 mA), and AC (2 mA peak-to-peak, 20 Hz square wave). These were compared to an Oral Baseline Absorption Group (sublingual diffusion in the absence of stimulation) to determine statistical significance of electrical stimulus; and a Subcutaneous Control Group (bolus injection) to discern therapeutic significance. +DC stimulation (4mA) increased serum concentration 28x with high statistical significance (p-value=0.0008). -DC stimulation (-4mA) increased serum concentration by 19x with borderline significance (p=0.032). AC (20 Hz) stimulus (2mA peak-peak) increased serum concentration by 10x, but was not statistically significant. The absorption rate of octreotide was also calculated for each group and compared at t=10 minutes and t=30 minutes. The absorption rate of the +DC group was 28x greater than that of Baseline Group and was statistically significant (p=0.0008). The absorption rate of the -DC group was 19x greater than that of the Baseline Group and was statistically significant (p=0.032). The absorption rate of the AC group was 10x greater than the Baseline Group but was not statistically significant (p=0.135). While none of the sublingual groups reached therapeutically significant serum concentrations, therapeutic levels of sublingually-delivered octreotide could potentially be achieved by extending octreotide exposure and stimulation time, coupled with utilizing sublingual octreotide in higher concentrations. This research was a necessary first step in successful realization of the SEP device.

Thesis (M.Phil.) - University of Queensland, 2006. / Includes bibliography.

Pharmacological treatment of Parkinson's disease involves frequent dose adjustment, complex dose regimes. Also oral antiparkinsonian drugs suffer from the first pass effect, and a variable absorption in the gastrointestinal tract. The transdermal route is an advantageous alternative, as shown by the recent commercialization of a passive patch containing rotigotine (Neupro®). In this work, transdermal iontophoretic delivery of six drugs was performed, using side-by-side diffusion cells. The best candidates for iontophoretic delivery were pramipexole, selegiline, and piribedil. Trihexyphenidyl, entacapone and pergolide are poor candidates and probably would require patches of impractical size.

The main technology currently used in diabetic care, monitors blood glucose and involves an invasive “fingerstick” step. However, low patient compliance and non-continuous glucose monitoring imply poor management of diabetes through this technology, which could lead to adverse and potentially life threatening conditions. In this context, non-invasive glucose sensing appears as an alternative that can bring a change in the prevention and management of the diabetic condition, promising to eliminate patient resistance towards more frequent monitoring and, hence, considerably improving diabetic’s control over glycaemia. However, no non-invasive technology has yet succeeded on the market over the long term. The research field is therefore open to innovative and performant non-invasive technologies. This thesis presents the development of a non-invasive biosensor which as a core principle accesses individual, privileged glucose pathways in the skin (such as hair follicles), allowing the extraction of glucose directly from the interstitial fluid, via reverse iontophoresis (RI). The transdermally extracted glucose is then electrochemically detected in a small size sensor with very high sensitivity. A fully developed technology based on this principle will not require fingerpricking and would thus eliminate users’ main barrier to glucose monitoring. The developed sensor is enzymatic (using glucose oxidase), which electrochemically detects the produced H2O2; while the electrode material is graphene produced by Chemical Vapour Deposition, a promising carbon nanomaterial platform for biofunctionalisation and biosensing. The sensor is a miniature one (typically of 9 mm2 area, containing 24 μL of gel encasing the enzyme), with demonstrated performance parameters that are highly competitive (sensitivity of 2.89 μA.mM-1.cm-2 and limit of detection down to 1 μM), with high specificity towards glucose. The combination of this sensor with glucose extraction by reverse iontophoresis was then validated (with proportionality between subdermal and extracted glucose concentrations demonstrated); as well as enhanced extraction through targeting of hair follicles with the miniature device. The electrochemical determination of glucose concentration was further confirmed by 1H quantitative-NMR detection of glucose. Finally, several such sensors were integrated in a multiplex configuration, and independent sensing, with no cross-talk was demonstrated. The steps demonstrated and implemented so far are proof-of-concept of a highly promising non-invasive, transdermal, future technology for diabetic care.

Thesis (Master)--İzmir Institute of Technology, İzmir, 2004. / Includes bibliographical references (leaves. 62-67).