DOCSLIB.ORG

Improvement of Dermatitis by Iontophoretically Delivered Antisense Oligonucleotides for Interleukin-10 in NC/Nga Mice

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Improvement of Dermatitis by Iontophoretically Delivered Antisense Oligonucleotides for Interleukin-10 in NC/Nga Mice Gene Therapy (2004) 11, 317–324 & 2004 Nature Publishing Group All rights reserved 0969-7128/04 $25.00 www.nature.com/gt RESEARCH ARTICLE Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice T Sakamoto1, E Miyazaki1, Y Aramaki1, H Arima1,3, M Takahashi1, Y Kato2, M Koga2 and S Tsuchiya1 1School of Pharmacy, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo, Japan; and 2Department of Dermatology, Tokyo Medical University, Shinjuku, Shinjuku-ku, Tokyo, Japan IL-10 is overexpressed in skin lesions of atopic dermatitis distributed in the epidermis and upper dermis. Topically (AD) patients and believed to be an important factor in the delivered AS6 decreased the levels of mRNA and protein of pathogenesis of the disease. Thus the regulation of IL-10 IL-10 in the lesions of NC/Nga mice, with no effect on IL-4 production is a potential solution for immunotherapeutic levels. The dorsal lesions of NC/Nga mice disappeared with intervention in AD. We examined the topical delivery of an repeated topical application of AS6. Topically delivered AS6 antisense oligonucleotide for mouse IL-10 (AS6) and the showed an inhibitory effect on the production of IL-10 in the therapeutic effect on the skin lesions of NC/Nga mice, a skin lesions of NC/Nga mice and had a therapeutic effect on human AD model. Using an iontophoresis system, about the established dermatitis. 30% of the applied dose of AS6 penetrated the skin and was Gene Therapy (2004) 11, 317–324. doi:10.1038/sj.gt.3302171 Keywords: interleukin-10; antisense oligonucleotides; atopic dermatitis; NC/Nga mice; topical Introduction factor in the pathogenesis of AD.12,13 Thus, IL-10 is an important factor in the pathogenesis of AD, and the Atopic dermatitis (AD) is a chronically relapsing regulation of its production is a potential solution for inflammatory disorder with pruritic and eczematous immunotherapeutic intervention. skin lesions usually associated with elevated serum IgE NC/Nga mice are an inbred strain established from levels.1,2 The skin lesions of AD patients are character- Japanese fancy mice in 1957 by Kondo (Nagoya ized by the presence of an inflammatory infiltrate University, Nagoya, Japan). Matsuda et al14 proposed consisting of T lymphocytes, monocytes/macrophages, that the NC/Nga mouse would make an excellent eosinophils, and mast cells.3,4 These cells are involved in animal model for human AD. When kept in specific the pathogenesis and development of AD through the pathogen-free (SPF) conditions,14–16 the mice remain release of various cytokines and chemokines including healthy. But when kept under conventional conditions, IL-4, IL-5, IL-10, IL-13,5 GM-CSF,6 and RANTES (regu- they started to scratch themselves at about 8 weeks, at lated upon activation, normal T expressed and secreted).7 which time their skin became dry and scaly. Within the Of these cytokines/chemokines, IL-10 is overexpressed next several weeks, the mice developed lesions on the by monocytes/macrophages and the Th2 lymphocytes in ears, back, neck, and face. The lesions on the back spread the skin lesions of AD patients.8 In addition, IL-10 from the ears down to the middle of the back and augments the production of thymus and activation reached the posterior axillary line. Immunohistochemical regulated chemokine (TARC), which is a Th2-specific examination of the lesions in conventional NC/Nga mice chemokine and is known for overexpression in AD reveal hyperkeratosis, acanthosis, and parakeratosis, all lesions9 and in human keratinocytes treated by TNF-a of which resemble the typical features of the skin and IFN-g.10 Furthermore, as IL-10 inhibits the apoptosis observed in patients with AD.9,15 The lesions show of T cells activated by ligation of T-cell receptors and IL-2 lymphocyte infiltration with a high CD4/CD8 ratio, treatment,11 IL-10 may be involved in the dysregulated macrophage infiltration, and mast cell and eosinophil apoptosis of T cells in the skin lesions of AD. This degranulation. In addition, the level of IgE in the blood dysregulated apoptosis is considered to be an important gradually increases to high levels.2 Although these immunological, histological, and biochemical changes of NC/Nga mice kept in conventional conditions Correspondence: S Tsuchiya, School of Pharmacy, Tokyo University of resemble human AD,14 the mechanisms are not fully Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, clear yet. Japan 3Present address: Graduate School of Pharmaceutical Sciences, Kumamoto Antisense oligonucleotides (AS-ODNs) designed to University, 5-1, Oe-honmachi, Kumamoto, Kumamoto 862-0973, Japan hybridize specifically to heterogenous nuclear RNA or Received 07 February 2003; accepted 19 September 2003 mature mRNA sequences have been shown to inhibit Antisense oligonucleotides for IL-10 alleviate dermatitis T Sakamoto et al 318 the expression of numerous genes both in vitro and Distribution and stability of AS6 in vivo.17,18 We have reported that AS6, the 18-mer We evaluated the ability of an iontophoresis system to phosphorothioate AS-ODN directed against the se- deliver AS6 into conventional NC/Nga mouse skin at 12 quence in the 30-untranslated region of mouse IL-10 weeks of age in vivo. On topical application of 1 mCi of mRNA, powerfully inhibited the production of IL-10 in [32P]-AS6 with iontophoresis, approximately 30% of the RAW264.7, a mouse macrophage-like cell line, by an dose was observed in the skin under the cathodal gel, antisense mechanism.19 In addition, Ohmen et al8 while about 35% remained in the cathodal gel (Figure revealed that the IL-10-producing cells were CD14 þ 2a). Only a negligible level of radioactivity was observed monocytes localized at the dermal perivascular infiltrate in the anodal gel, the skin under it, and other tissues. On in human AD lesions. Therefore, AS6 may have potential the other hand, no radioactivity of [32P]-AS6 was in the treatment of AD if it can be delivered to the site of observed in the skin under the cathodal gel when current the skin where IL-10-producing cells are located. How- was not applied (data not shown). ever, AS-ODNs have difficultly permeating the skin To evaluate the localization of AS6 in the skin, skin through the stratum corneum due to a lower lipophilicity was cross-sectioned after iontophoresis of AS6 labeled and a relatively high molecular weight. To date, with rhodamine (Rho) at the 50 end (Rho-AS6). Fluores- iontophoresis is known as a method of positively cence of Rho was observed at the epidermis and upper delivering ionized drugs, which enables the transdermal dermis, and iontophoresis allowed Rho-AS6 to penetrate administration of compounds with large molecular the stratum corneum although Rho-AS6 remained in the weights.20,21 Accordingly, the method is now attracting stratum corneum (Figure 2b, IP ( þ )). On the other hand, attention as a noninvasive method, and allows AS-ODNs no fluorescence was observed in the stratum corneum, to penetrate the stratum corneum and be distributed in when no current was applied (Figure 2b, IP (À)). the skin.22 Thus, we expect that iontophoresis can deliver To check the stability of AS6 in the skin of NC/Nga AS6 to regions where target cells are producing IL-10 in mice, AS6 was extracted from the skin following the lesions of AD. In the present study, we evaluated the iontophoresis and subjected to gel electrophoresis. In therapeutic effects of topically delivered AS6 on derma- Figure 2c, radioactivity gave a single band at the same titis on the dorsal skin of NC/Nga mice, as a human AD mobility as a marker, [32P]-AS6 (18 mer) (lane 1). The model. Results Cytokine and IgE levels in the skin lesion of NC/Nga mice NC/Nga mice have been reported to develop eczema- tous skin lesions when kept in conventional surround- ings14–16 but cytokine levels in the lesions of NC/Nga mice are not reported. IL-10, IL-4, and IgE levels in the lesions were determined in mice kept under conven- tional and SPF conditions for different feeding periods. IL-10 and IL-4 productions increased after 8 weeks of age (Figure 1). In addition, the IgE level in the skin of conventional mice at 12 weeks of age was much higher than that of mice kept under SPF conditions (Figure 1). Figure 2 Distribution and stability of topically delivered AS6 in NC/Nga mice. [32P]-AS6 was applied at 20 nmol including 1 mCi in the cathodal gel. Iontophoresis was carried out under conventional conditions (10 V, 0.3 mA, 2.5 h) in NC/Nga mice. (a) Radioactivity recovered after topical application of [32P]-AS6 with iontophoresis. Others included blood, liver, spleen, and kidney. Each value represents the mean7s.e. for six mice in each group. (b) Cross-sections showing the distribution of Rho-AS6 in NC/ Nga mouse skin. Rho-AS6 was applied at 20 nmol in the cathodal gel. Fluorescent images were obtained immediately after application using confocal laser scanning microscopy. IP ( þ ), iontophoresis was carried out; IP (À), iontophoresis was not carried out. Similar results were obtained in three separate experiments. (c) The stability of [32P]-AS6 in the skin of NC/ Figure 1 Determination of IL-10, IL-4, and IgE productions in the skin Nga mice. Lane 1, mixture of intact 18 mer [32P]-AS6 and [g-32P]-ATP; lesions of NC/Nga mice. IL-10, IL-4, and IgE productions were determined lane 2, immediately; lane 3, 24 h; lane 4, 48 h after topical application of in the skin of NC/Nga mice of various ages under SPF (&) and [32P]-AS6.
Load more

Recommended publications
  • Thesis Submitted By
    University of Bath PHD A study of low voltage polyacrylamide gel electrophoresis as a means of providing controlled drug release Kumar, Ravinder Award date: 1986 Awarding institution: University of Bath Link to publication Alternative formats If you require this document in an alternative format, please contact: [email protected] General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 11. Oct. 2021 A Study of Low Voltage Polyacrylamide Gel Electrophoresis as a means of providing Controlled Drug Release A thesis submitted by Ravlnder Kumar for the degree of Doctor of Philosophy of the University of Bath 19 86 Copyright Attention is drawn to the fact that copyright, of this thesis rests with its author. A copy of this thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without the prior written consent of the author.
    [Show full text]
  • Associated Problems of Protein Electrophoresis, Staining and Densitometry*
    ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 8, No. 5 Copyright © 1978, Institute for Clinical Science Associated Problems of Protein Electrophoresis, Staining and Densitometry* BENNIE ZAK, Ph.D.,f EUGENE S. BAGINSKI, Ph.D.,* and EMANUEL EPSTEIN, Ph.D.§ Departments of Clinical Pathology: t Wayne State University School of Medicine and Detroit General Hospital, Detroit, MI 48201 f St. Joseph Mercy Hospital, Pontiac, Ml 48053 § William Beaumont Hospital, Royal Oak, MI 48072 ABSTRACT The process of electrophoresis, a separation phenomenon, is mistakenly understood to include the sequential processes ancillary to analyte resolu­ tion, that is, staining and quantification, where the latter could be elution followed by photometry or integrating-calculating-densitometry. The theories involved in electrophoresis itself are well worked OuFand equally well understood but the problems which are associated with separation, chemical reaction to generate a chromogen and quantification, perhaps partly forgotten and perhaps partly ignored, are taken up and described here. They include albumin trail, resolution, unequivalent staining, prestaining and the densitometry problems associated with band widths, opacity effects and polychromaticities. Introduction and perfected of the three phases in terms of accomplishing its purpose with the Any discussion of protein electro­ least problems, that is to separate proteins phoresis should include electrophoresis into several well resolved zones by the itself, and the sequential phases as­ simplest means possible.
    [Show full text]
  • Information to Users
    INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter &ce, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely afreet reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand comer and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back o f the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6” x 9” black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. UMI A Bell & Howell Io5)nnaüon Company 300 North Zed) Road, Ann Arbor MI 48106-1346 USA 313/761-4700 800/521-0600 LIQUID CRYSTAL AND HYDROPHILIC GEL MEDIA FOR IONTOPHORESIS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Manesh A.
    [Show full text]
  • (CFTR) Allelic Variants Relate to Shifts in Faecal Microbiota of Cystic Fibrosis Patients
    Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Allelic Variants Relate to Shifts in Faecal Microbiota of Cystic Fibrosis Patients Serena Schippa1., Valerio Iebba1*., Floriana Santangelo1, Antonella Gagliardi1, Riccardo Valerio De Biase2, Antonella Stamato2, Serenella Bertasi2, Marco Lucarelli3, Maria Pia Conte1", Serena Quattrucci2" 1 Public Health and Infectious Diseases Department, Microbiology Unit, ‘Sapienza’ University of Rome, Rome, Italy, 2 Regional Cystic Fibrosis Centre, Paediatrics and Infant Neuropsychiatry Department, ‘Sapienza’ University of Rome, Rome, Italy, 3 Department of Haematology and Cellular Biotechnologies, Sapienza University of Rome, Rome, Italy Abstract Introduction: In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF). CFTR mutations (F508del is the most common) lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age. Methods: Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure. Results: Patients were classified by two different criteria: 1) presence/absence of F508del mutation; 2) disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness.
    [Show full text]
  • Microalgae Amino Acid Extraction and Analysis At
    Microalgae amino acid extraction and analysis at nanomolar level using electroporation and capillary electrophoresis with laser-induced fluorescence detection Reine Nehmé, Carla Atieh, Syntia Fayad, Bérengère Claude, Agnès Chartier, Mona Tannoury, Fatma Elleuch, Slim Abdelkafi, Chantal Pichon, Philippe Morin To cite this version: Reine Nehmé, Carla Atieh, Syntia Fayad, Bérengère Claude, Agnès Chartier, et al.. Microalgae amino acid extraction and analysis at nanomolar level using electroporation and capillary electrophoresis with laser-induced fluorescence detection. Journal of Separation Science, Wiley-VCH Verlag, 2017,40 (2), pp.558-566. 10.1002/jssc.201601005. hal-01618682 HAL Id: hal-01618682 https://hal.archives-ouvertes.fr/hal-01618682 Submitted on 25 Jun 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Microalgae amino acid extraction and analysis at nanomolar level using electroporation and capillary electrophoresis with laser-induced fluorescence detection Reine
    [Show full text]
  • Determination and Implications of Electroosmotic Transport In
    DETERMINATION AND IMPLICATIONS OF ELECTROOSMOTIC TRANSPORT IN THE BRAIN by Yifat Guy BS, University of Pittsburgh, 2004 Submitted to the Graduate Faculty of Arts and Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2011 UNIVERSITY OF PITTSBURGH Graduate Arts and Sciences This dissertation was presented by Yifat Guy It was defended on December 15, 2010 and approved by Dr. Shigeru Amemiya, Professor, Department of Chemistry Dr. Adrian Michael, Professor, Department of Chemistry Dr. Mats Sandberg, Professor, Department of Anatomy and Cell Biology, Gothenberg University Dissertation Advisor: Dr. Stephen G. Weber, Professor, Department of Chemistry ii Copyright © by Yifat Guy 2011 Reproduced with permission from: Guy Y, Sandberg M, Weber SG. Biophysical Journal. 2008;94(11):4561-4569. Guy Y, Muha RJ, Sandberg M, Weber SG. Analytical Chemistry. 2009;81(8):3001-3007. iii DETERMINATION AND IMPLICATIONS OF ELECTROOSMOTIC TRANSPORT IN THE BRAIN Yifat Guy, PhD University of Pittsburgh, 2011 Electroosmotic flow is a bulk fluid flow that influences solute transport through capillary conduits and porous material under the influence of an electric field. The magnitude of electroosmotic flow is proportional to the ζ-potential of the capillary or porous material. A porous material such as living tissue would need to have an appreciable ζ-potential to create electroosmotic flow in the interstitial space. Transporting solutes in and out of tissue by virtue of electroosmotic flow in principle has advantages such as avoiding pressure effects and sample dilution that accompany micropush-pull and microdialysis approaches. In order to assess the viability of this approach, it is necessary to know the ζ-potential in the tissue of interest.
    [Show full text]
  • Microelectrophoresis of Semiconductive Quantum Dots
    Microelectrophoresis of Semiconductive Quantum Dots By Mengke Han A thesis submitted for the fulfilment of the degree of Master of Philosophy in the Faculty of Sciences School of Physical Sciences Aug 2017 Declaration of Authorship I certify that this work contains no material which has been accepted for the award of any other degree or diploma in my name in any university or other tertiary institution and, to the best of my knowledge and belief, contains no material previously published or written by another person, except where due reference has been made in the text. In addition, I certify that no part of this work will, in the future, be used in a submission in my name for any other degree or diploma in any university or other tertiary institution without the prior approval of the University of Adelaide and where applicable, any partner institution responsible for the joint award of this degree. I give consent to this copy of my thesis when deposited in the University Library, being made available for loan and photocopying, subject to the provisions of the Copyright Act 1968. I also give permission for the digital version of my thesis to be made available on the web, via the University's digital research repository, the Library Search and also through web search engines, unless permission has been granted by the University to restrict access for a period of time. Signed: Date: II Table of contents Declaration of Authorship .................................................................................. II Abstract ..............................................................................................................
    [Show full text]
  • Iontophoresis: Fundamentals, Developments and Application
    Iontophoresis: fundamentals, developments and application Edina Vrani} Department of Pharmaceutical Technology, University of Sarajevo, Faculty of Pharmacy, ^ekalu{a 90, Bosnia and Herzegovina Abstract enhancers that can increase the percutaneous absorption of therapeutic agents. The skin is an excellent barrier to the transport of charged compounds and large molecules. Many substances of present and potential therapeutic utility carry charge at Definition physiological pH, have high molecular weights and/or are hydrophilic and, consequently, do not transport well Iontophoresis is a process or a technique which involves across the skin. Pathways for the transport of small ions the transport of ionic (charged) molecules into a tissue by do appear to exist through the skin and flow along these the passage of a direct electric current through an elec- pathways can be substantially enhanced by iontophore- trolyte solution containing the ionic molecules to be sis. delivered, using an appropriate electrode polarity. It involves the transfer of ions into the body by an electro- Key words: iontophoresis, transport, patches, applica- motive force. Ions with positive charge are driven into tion the skin at the anode and those with negative charge at the cathode. Introduction This technique is used to enhance the transdermal trans- Drug delivery technology allows the right dose of an port of drugs by applying a small current through a reser- active pharmaceutical ingredient to be delivered at the voir that contains ionized species of drug. Positive or right time, and most importantly, to the right site. It is negative electrodes are placed between the drug reservoir playing an increasingly important role in lowering the and the skin.
    [Show full text]
  • NIH Public Access Author Manuscript Anal Chem
    NIH Public Access Author Manuscript Anal Chem. Author manuscript; available in PMC 2009 November 15. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Anal Chem. 2008 November 15; 80(22): 8635±8641. doi:10.1021/ac801547a. Electroosmotic flow and its contribution to iontophoretic delivery Natalie R. Herr1, Brian M. Kile1, Regina M. Carelli2, and R. Mark Wightman1,* 1Department of Chemistry and Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290 2Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290 Abstract Iontophoresis is the movement of charged molecules in solution under applied current using pulled multi-barrel glass capillaries drawn to a sharp tip. The technique is generally non-quantitative, and to address this, we have characterized the ejection of charged and neutral species using carbon-fiber electrodes attached to iontophoretic barrels. Our results show that observed ejections are due to the sum of iontophoretic and electroosmotic forces. Using the neutral, electroactive molecule 2-(4- nitrophenoxy) ethanol (NPE), which is only transported by electroosmotic flow (EOF), a positive correlation between the amount ejected and the diameter of each barrel's tip was found. In addition, using various charged and neutral electroactive compounds we found that, when each compound is paired with the EOF marker, the percentage of the ejection due to EOF remains constant. This percentage varies for each pair of compounds, and the differences in mobility are positively correlated to differences in electrophoretic mobility. Overall, the results show that capillary electrophoresis (CE) can be used to predict the percentage of ejection that will be due to EOF.
    [Show full text]
  • Prelim Mechanical Latest.Qxd
    The following is the preliminary technical program and is subject to change. For the latest program, visit www.aiche.org/annual Preliminary Program 2006 AICHE ANNUAL MEETING November 12-17, 2006 San Francisco, California, San Francisco Hilton The most diverse, global, value-added Annual Meeting ever! Close to 700 technical sessions, 16 Topical Conferences, 4,500 engineers and scientists Discover the latest developments in alternative energy, rapid process development, nano- and biotechnology, process intensification, environ- mental technology, sustainability, reactions & separations, sensors, ChE education and other “hot growth” areas — and the implications for your organization Learn new ways to be more efficient and productive in the corporate, process-plant, R&D or academic work environment — Hear from experts what skills are vital for success in global business interactions Examine critical emerging technologies and how to put them to work to stay far ahead of your competition Plus new this year, CEOs and Government Leaders Roundtable The Annual Dankwertz Lecture Presented for the first time ever in the United States US-Japan Joint Topical Conference on Medical Engineering, Drug Delivery Systems and Therapeutic Systems 06 ® Annual Meeting, San Francisco, CA Register now! www.aiche.org/annual; 800.242.3463 or 212.591.8100 (Outside the US) Preliminary Technical Program – Annual Meeting, San Francisco, CA, November 12–November 17 12–November CA, November – Annual Meeting, San Francisco, Program Technical Preliminary SUNDAY, 12 NOVEMBER
    [Show full text]
  • Electrochemical Methods for Drug Characterisation and Transdermal Delivery Capillary Zone Electrophoresis, Conductometry and Iontophoresis
    Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 302 Electrochemical Methods for Drug Characterisation and Transdermal Delivery Capillary Zone Electrophoresis, Conductometry and Iontophoresis BY NADIA MERCLIN ACTA UNIVERSITATIS UPSALIENSIS UPPSALA 2003 Dissertation presented at Uppsala University to be publicly examined in B21, Uppsala Biomedical Centre, Uppsala, Friday, December 5, 2003 at 10:15 for the degree of Doctor of Philosophy (Faculty of Pharmacy). The examination will be conducted in English. ABSTRACT Merclin, N., 2003. Electrochemical Methods for Drug Characterisation and Transdermal Delivery: Capillary Zone Electrophoresis, Conductometry and Iontophoresis. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 302. 40 pp. Uppsala. ISBN 91-554-5803-3. This thesis concerns the development and utilisation of techniques for characterisation and transdermal delivery of various systems for pharmaceutical applications. The degree of dissociation of drug molecules and the mobilities of the different species formed are essential factors affecting the rate of drug delivery by iontophoresis. Hence, determination of drug mobility parameters and equilibrium constants are important for the development of iontophoretic systems. With capillary zone electrophoresis using a partial filling technique and methyl-E-cyclodextrin as chiral selector, the enantiomers of orciprenaline were separated. The association constants between the enantiomers of the drug and the selector were also evaluated. Precision conductometry studies were performed for the hydrochloride salts of lidocaine and 5-aminolevulinic acid in aqueous propylene glycol and water as media, respectively. Iontophoresis is a technique for drug delivery where charged molecules are transported into and through skin by application of a weak direct electrical current.
    [Show full text]
  • Fundamental Capillary Electrophoresis: an Evaluation of Electrokinetic Sampling Cindy Ann Mleziva Blake Seton Hall University
    Seton Hall University eRepository @ Seton Hall Seton Hall University Dissertations and Theses Seton Hall University Dissertations and Theses (ETDs) Spring 5-2000 Fundamental Capillary Electrophoresis: An Evaluation of Electrokinetic Sampling Cindy Ann Mleziva Blake Seton Hall University Follow this and additional works at: https://scholarship.shu.edu/dissertations Part of the Chemistry Commons Recommended Citation Mleziva Blake, Cindy Ann, "Fundamental Capillary Electrophoresis: An Evaluation of Electrokinetic Sampling" (2000). Seton Hall University Dissertations and Theses (ETDs). 1255. https://scholarship.shu.edu/dissertations/1255 Fundamental Capillary Electrophoresis: An Evaluation of Electrokinetic Sampling by Cindy Ann Mleziva Blake Dissertation submitted to the Department of Chemistry of Seton Hall University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY In Chemistry May 2000 South Orange, New Jersey We certify that we have read this thesis and that in our opinion it is adequate in scientific scope and quality as a dissertation for the degree ofDoctor of Philosophy. APPROVED: Nici?olas H. Snow, Ph.D. Research Director Richard heardy, Ph.D. Chainnan, Department ofChemistry Abstract Fundamental Capillary Electrophoresis: An Evaluation of Electrokinetic Sampling Capillary electrophoresis has become a powerful separation technique in fields of biochemical separations, inorganic ions, and chiral separations. The technique has experienced exponential growth since the historic publication ofZone Electrophoresis in Open-Tubular Glass Capillaries by Lukacs and Jorgenson in 1981. However, the use of capillary electrophoresis as a primary research analysis tool still remains to be seen in many pharmaceutical laboratories. One ofthe main reasons for this is that it remains difficult to validate CE methods using the criteria ofquantitation and accuracy posed by the current government regulating agencies, as developed for high performance liquid chromatography and gas chromatography methods.
    [Show full text]