Topical Nail Products and Ungual Drug Delivery - 1st Edition
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Topical Nail Products
and Ungual Drug Delivery
EditEd by
S. Narasimha Murthy
Howard I. Maibach
Boca Raton London New York
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Contents
Preface......................................................................................................................vii
Editors........................................................................................................................ix
Contributors’ Biographies..........................................................................................xi
Chapter 1 The Nail: Anatomy, Physiology, Diseases, and Treatment................... 1
Sudaxshina Murdan
Chapter 2 Permeability of the Nail Plate............................................................. 37
Jinsong Hao and S. Kevin Li
Chapter 3 Topical Nail Formulations................................................................... 61
H. N. Shivakumar, Michael A. Repka, Sudaxshina Murdan, and
S. Narasimha Murthy
Chapter 4 Approaches to Enhance Ungual and Trans-Ungual
Drug Delivery...................................................................................... 87
H. N. Shivakumar, Abhishek Juluri, Michael A. Repka,
and S. Narasimha Murthy
Chapter 5 In Vitro and In Vivo Models to Evaluate Topical Nail
Formulations...................................................................................... 123
Anroop B. Nair, Xiaoying Hui, Majella E. Lane,
and S. Narasimha Murthy
Chapter 6 Hydration-Controlled Nail System for the Evaluation of
Topical Formulations and a Novel Nail Sampling Device................ 149
Rania Elkeeb, Xiaoying Hui, and Howard I. Maibach
Chapter 7 Bioengineering of the Nail: Transonychial Water Loss and
Imaging Techniques, an Overview.................................................... 157
Rania Elkeeb and Howard I. Maibach
Chapter 8 Trans-Ungual Iontophoresis and Physical Drug Delivery
Enhancement..................................................................................... 165
Jinsong Hao and S. Kevin Li
v
vi Contents
Chapter 9 Pharmacokinetics of Drugs in the Nail Apparatus........................... 187
Danièle Debruyne and Antoine Coquerel
Chapter 10 Onychopharmacokinetics: Proposed Model Insight......................... 215
Rania Elkeeb, Xiaoying Hui, Laila Elkeeb, Ali Alikhan, and
Howard I. Maibach
Chapter 11 Photodynamic Therapy of Nail Diseases.......................................... 225
Ryan F. Donnelly, Corona M. Cassidy, and Michael M. Tunney
Chapter 12 Nail as a Surrogate for Investigating Drug Use................................ 245
Katarzyna Madej
Preface
Nail diseases, which include infections and inflammatory disorders, could affect
human beings at any age. The diseases can result in feelings of inadequacy and
depression in patients and affect their quality of life significantly.
Oral and topical delivery of drugs have been the most common approaches to
treat nail diseases. Topical therapy is the most preferred mode of drug delivery,
due to patient compliance and convenience. Development of topical formulations
to deliver effective amounts of drugs into the nail apparatus is highly challenging.
This book provides a comprehensive review regarding the various nail diseases,
topical formulations, drug delivery approaches, and unguokinetics of drugs. The
chapters are contributed by pioneers in ungual drug delivery.
vii
Editors
S. Narasimha Murthy, PhD, is an associate professor at the University of Mississippi
School of Pharmacy, University, Mississippi. After obtaining his PhD in pharmaceu-
tics from Bangalore University, India, Dr. Murthy worked as a research associate at
the Roswell Park Cancer Institute, Buffalo, New York, and as an assistant professor
at Ohio Northern University, Ada, Ohio. He has published more than 60 research
articles in the field of dermal and ungual drug delivery. Dr. Murthy also edited
the textbook Dermatokinetics of Therapeutic Agents. He has been on the editorial
boards of several pharmaceutical journals.
Howard I. Maibach, PhD, is currently serving as a professor of dermatology at
the University of California, San Francisco, California. He obtained his MD from
Tulane University, New Orleans, Louisiana, in 1955. Later, he served in faculty posi-
tions in various levels at the University of California, San Francisco. Dr. Maibach
has published more than 2520 articles. He has been on the editorial board of more
than 30 scientific journals and is a member of 19 professional societies including the
American Academy of Dermatology, San Francisco Dermatological Society, and the
Internal Commission on Occupation Health.
ix
Contributors’ Biographies
Ali Alikhan, MD, is a resident in dermatology at the Mayo Clinic Department of
Dermatology. He received his Bachelors in Science from Kent State Univserity and
Medical Degree from University of California Davis School of Medicine, in addi-
tion to completing a transitional residency at MacNeal Hospital in Berwyn, Illinois.
He has published well over 60 journal articles and book chapters, and has presented
at several national meetings. He has published on melanoma, vitiligo, hidradenitis
suppurativa, onychomycosis, medical education, psoriasis, acne, rosacea, allergic
contact dermatitis, Fox-Fordyce disease, and dermatopharmacology, among other
topics. He holds several local and national leadership positions, and is a reviewer for
numerous dermatology and non-dermatology journals.
Corona M. Cassidy, PhD, is an honorary research fellow in the School of Pharmacy
at Queen’s University Belfast. She obtained an MPharm (First Class) in 2005 and a
PhD in pharmaceutical microbiology in 2010, and has since held positions in com-
munity pharmacy, academia, and the pharmaceutical industry, where she is based
at present. She has research interests in clinical pharmacy and pharmaceutical
manufacturing/production technologies.
Antoine Coquerel, PhD, is a neurologist and pediatrician who holds a doctorate degree
in neuropsychopharmacology. He has been the head of the Pharmacology Department
and laboratory at the University Hospital of Caen, France, since 1999. Dr. Coquerel is
also qualified to manage research in the fields of cell biology and neuropsychopharma-
cology. Since 1999, he has been serving as the head of the Regional Pharmacovigilance
Centre of Lower Normandy and the Centre for Evaluation and Information on Drug
Dependence for the northwest of France. He is also the director of teaching of the
pharmacology of Caen faculty of medicine. Dr. Coquerel does clinical research at
the University of Caen as well as the University hospital. He leads a mixed research
team at the University of Caen, Basse-Normandie, France. Her clinical research at the
University of Caen is focused on “drug and driving,” “aging and drugs,” and chronobi-
ology in healthy humans. He also performs experimental research on drug dependence
in rats and mice. He has 57 publications and is also a coauthor of a French handbook of
pharmacology (Masson, Paris, 2002). He is also an active member of French Society of
Pharmacology and Therapeutics and the National College of Medical Pharmacology.
He is an expert pharmacologist in the scientific committee of the regional clinical
research management as well as an expert in the French drug safety agency (AFSSaPS).
Danièle Debruyne, PhD, is a senior scientist in the Department of Pharmacology
at the University Hospital Centre of Caen, France. Dr. Debruyne manages the thera-
peutic monitoring of drugs mainly used in infectious and neurological diseases and
in the prevention of graft rejection, with the objective being better efficacy and minor
toxicity of the administered treatments owing to an optimal management; according
xi
xii Contributors’ Biographies
to an agreement with the French Office of Drugs and Drug Addiction, Dr. Debruyne
assumed the scientific responsibility of the analysis of illicit and licit recreational
drugs that circulate in France to evaluate their dangerousness. Within the research
team entitled “Laboratory of Methodological Developments for Positron Emission
Tomography (PET),” Dr. Debruyne coordinates the biological characterization
(including blood and tissue distribution, metabolism, evaluation of the in vitro and
in vivo specific binding) of the new PET radiotracers developed by radiochemists.
Dr. Debruyne has been recognized as an expert by the French Agency for the Safety
of Health Products in the field of experimental pharmacokinetics. Dr. Debruyne has
published five original research or review articles (on a total of 76 papers indexed in
PubMed) concerning antifungal drugs.
Ryan F. Donnelly, PhD, is reader in pharmaceutics in the School of Pharmacy at
Queen’s University Belfast, UK. Dr. Donnelly’s research is centered on design and
physicochemical characterization of advanced polymeric drug delivery systems for
transdermal and topical drug delivery, with a strong emphasis on improving thera-
peutic outcomes for patients. His bioadhesive patch design was used in successful
photodynamic therapy of over 100 patients with neoplastic and dysplastic gyneco-
logical conditions. This technology has now been licensed to Swedish Pharma AB,
for whom Dr. Donnelly acts as a technical director. His microneedle technology is
currently undergoing commercial development by two leading pharmaceutical com-
panies. Still at a relatively early stage of his career, he has authored over 200 peer-
reviewed publications, including three patent applications, three textbooks, seven
book chapters, and approximately 90 full papers. He has been an invited speaker at
several national and international conferences. Dr. Donnelly is the associate editor
of Recent Patents on Drug Delivery & Formulation and a member of the editorial
advisory boards of Pharmaceutical Technology Europe and Journal of Pharmacy
and Bioallied Sciences and is a visiting scientist at the Norwegian Institute for
Cancer Research, where he is an associate member of the Radiation Biology Group.
Dr Donnelly is the current holder of the Royal Pharmaceutical Society’s pres-
tigious Science Award and is a previous winner of an Innovation Leader Award
from the NHS Research & Development Office, a research scholarship from the
Research Council of Norway, and the Pharmaceutical Society of Northern Ireland’s
Gold Medal.
Laila Elkeeb, MD, is a fellow in dermatopathology at the University of Cincinnati
Dermatology department. She completed her dermatology residency and a clini-
cal trials fellowship from the University of California, Irvine. She also completed
a Melanoma and Cutaneous Oncology fellowship from the University of California,
San Francisco. Dr. Elkeeb has several years of research experience in the field of der-
matology. She was a co-investigator on several studies that involved; skin cancer biol-
ogy, laser and light therapy of dermatological diseases, psoriasis, rosacea, acne, and
dermatopharmacology. She has published several journal articles, and has presented
at several national meetings. Dr. Elkeeb has published in the field of skin cancer biol-
ogy, laser and light therapy of dermatological diseases, phototoxicity, photoallergic
dermatitis, dermatopharmacology, rosacea, onychomycosis, and dermatopathology.
Contributors’ Biographies xiii
Rania Elkeeb, PhD, is a researcher at Surge Lab, Department of Dermatology,
University of California, San Francisco, California. She received her bachelor of
pharmacy from Petra University, formerly Jordan University for Women, Amman,
Jordan, in 1997. Dr. Elkeeb obtained her PhD in pharmaceutics and industrial phar-
macy from the Massachusetts College of Pharmacy and Health Sciences, Boston,
Massachusetts, in May 2005. She has done her postdoctoral training in dermato-
pharmacokinetics and onychopharmacokinetics as relates to their biologic/clinical
effects in man and animals in the Department of Dermatology at the University
of California, San Francisco, California, in 2008. She served as an adjunct assis-
tant professor of pharmaceutical sciences at the Massachusetts College of Pharmacy
and Health Sciences, Worcester, Massachusetts. Her current research interests are
trans-ungual and transdermal drug delivery and their absorption efficiency; derma-
topharmacokinetic and onychopharmacokinetics analysis; and transfollicular drug
delivery.
Jinsong Hao, PhD, obtained her PhD in pharmaceutics from Shenyang
Pharmaceutical University, China. After her graduation, she worked at Shenyang
Pharmaceutical University (China), National University of Singapore (Singapore),
and Nova Southeastern University (United States). She is currently a research assis-
tant professor in the College of Pharmacy at the University of Cincinnati (United
States). Her research is in the field of drug delivery. She has published more than 40
research articles in transdermal, transscleral, transcorneal, and trans-ungual drug
delivery.
Xiaoying Hui, MD, is an associate research dermatologist in the Department of
Dermatology at the University of California, San Francisco, California. He has
worked as a principal investigator in Dr. Howard Maibach’s laboratory for 20 years.
His major interests are dermatotoxicokinetics and risk assessment modeling of
environmental chemicals following human skin absorption; antifungal drugs trans-
ungual delivery and absorption efficiency; dermal absorption and transdermal
delivery; and dermatopharmacokinetic analysis. He has published more than 60
peer-reviewed research articles and is the author of 17 book chapters.
Abhishek Juluri, is a graduate student in the Department of Pharmaceutics at the
University of Mississippi, University, Mississippi. He is an NIH predoctoral fellow
and a member of the American Association of Pharmaceutical Scientists and Rho
Chi. Mr. Juluri received his bachelor’s degree in 2009 from Kakatiya University,
India.
Majella E. Lane, PhD, is a senior lecturer of pharmaceutics in the School of
Pharmacy at University College London. To date, she has been involved in the
supervision of over 20 PhD students. She is a visiting professor in the Department
of Pharmaceutical Sciences at the University of Michigan, Ann Arbor, Michigan.
Over the years, she has contributed to more than 60 peer-reviewed articles and 10
book chapters and serves on the editorial boards of several pharmaceutical science
journals. Her major research interests are in the application of physical chemistry to
xiv Contributors’ Biographies
tissue characterization and modulation with special reference to the skin and nail.
Her research group collaborates worldwide and uses a range of biophysical tech-
niques (attenuated total reflectance-Fourier transform infra-red spectroscopy, confo-
cal Raman spectroscopy, high-speed differential scanning calorimetry) to probe the
mechanisms of skin penetration and its modulation. She also coordinates the Skin
Forum, which evolved from an Engineering and Physical Sciences Research Council
funded network on skin permeability.
S. Kevin Li, PhD, is an associate professor of pharmaceutics in the College of
Pharmacy at the University of Cincinnati, Cincinnati, Ohio. He is also an adjunct
associate professor in the College of Pharmacy at the University of Utah, Salt Lake
City, Utah. Dr. Li graduated summa cum laude from Brigham Young University,
Provo, Utah, where he obtained his bachelor’s degree in chemistry. Subsequently, he
earned his PhD in pharmaceutics and pharmaceutical chemistry from the University
of Utah under the supervision of Dr. William Higuchi and with the support of a pred-
octoral fellowship from Pharmaceutical Research and Manufacturers of America
(PhRMA) Foundation. Dr. Li has published more than 80 articles, patents, and book
chapters on transdermal, ocular, and trans-ungual drug delivery and noninvasive
pharmacokinetic study using MRI. He is a principal investigator and coinvestigator
of research grants funded by the National Institutes of Health (NIH) in the United
States. He has frequently served as a reviewer for scientific journals in pharma-
ceutical sciences, ophthalmology, and MRI research and a member in grant review
panels.
Katarzyna Madej, PhD, graduated from the Faculty of Chemistry at the Jagiellonian
University, Krakow, Poland, where she defended her master thesis. Her postgraduate
study took place at the Faculty of Chemistry in 1987–1991. In 1993, she defended
her doctoral thesis on “Development of computerized-aid potentiometric multi-
component titration methods.” Then, she was employed in the Institute of Forensic
Research, Krakow, Poland, for 7 years. In 1999, she began her career in the Faculty
of Chemistry at the Jagiellonian University as an assistant and from 2002 as an assis-
tant professor. Dr. Madej’s scientific work mainly concerns development and opti-
mization of analytical procedures for medicaments, especially psychotropic drugs,
in biological samples. Her research interests include clinical and forensic toxicology,
biological sample preparation techniques, and development of chromatographic and
capillary electrophoretic methods. She also participated actively in many national
and international conferences and symposia.
Howard I. Maibach, PhD, is currently serving as a professor of dermatology at
the University of California, San Francisco, California. He obtained his MD from
Tulane University, New Orleans, Louisiana, in 1955. Later, he served in faculty posi-
tions in various levels at the University of California, San Francisco. Dr. Maibach
has published more than 2520 articles. He has been on the editorial board of more
than 30 scientific journals and is a member of 19 professional societies including the
American Academy of Dermatology, San Francisco Dermatological Society, and the
Internal Commission on Occupation Health.
Contributors’ Biographies xv
Sudaxshina Murdan, PhD, is a senior lecturer in Pharmaceutics at the University
College London School of Pharmacy. She studied pharmacy at The University of
Nottingham and gained her PhD from The School of Pharmacy, University of London
(now UCL School of Pharmacy). Her research is in the fields of ungual drug delivery,
vaccine delivery, and in pharmacy and development education, and she has authored
over 40 peer-reviewed papers, over 70 conference papers, a number of book chap-
ters and articles in industry newsletters and student newspaper. She teaches on the
MPharm, MSc and PhD programs and is a fellow of the Higher Education Academy.
S. Narasimha Murthy, PhD, is an associate professor at the University of Mississippi
School of Pharmacy, University, Mississippi. After obtaining his PhD in pharmaceu-
tics from Bangalore University, India, Dr. Murthy worked as a research associate at
the Roswell Park Cancer Institute, Buffalo, New York, and as an assistant professor
at Ohio Northern University, Ada, Ohio. He has published more than 60 research
articles in the field of dermal and ungual drug delivery. Dr. Murthy also edited
the textbook Dermatokinetics of Therapeutic Agents. He has been on the editorial
boards of several pharmaceutical journals.
Anroop B. Nair, PhD, is an assistant professor in the College of Clinical Pharmacy
at King Faisal University, Al Ahasa, Saudi Arabia. He received his PhD in pharma-
ceutics from Jadavpur University, Kolkata, India. He was a postdoctoral fellow in
S. N. Murthy Research group at the University of Mississippi, University, Mississippi,
during which he worked extensively on the iontophoretic drug delivery in nail. He
is an active member of several pharmaceutical councils/forums and a reviewer for
several peer-reviewed journals in the field of pharmaceutics. He has authored more
than 50 peer-reviewed articles.
Michael A. Repka, PhD, is chair and professor of the Department of Pharmaceu
tics at the University of Mississippi, University, Mississippi, as well as the director
of the Center for Pharmaceutical Technology. Dr. Repka joined the faculty at Ole
Miss after receiving his PhD from the University of Texas College of Pharmacy and
founded a pharmaceutical research/development company that specializes in drug
delivery. His research interests include oral transmucosal and transdermal/transnail
delivery systems, as well as other novel dosage forms. Many of these systems are
directed toward the solubilization and delivery of poorly soluble bioactives via hot-
melt extrusion technology, which is a primary focus of his research. In the nail drug
delivery area, Dr. Repka worked on development of bioadhesive nail patches and nail
etching technology. Her publications include more than 70 peer-reviewed journal
articles and book chapters and well over 250 presentations at national/international
scientific meetings. She serves on the editorial advisory boards of six prestigious
journals, is an associate editor for AAPS PharmSciTech, and has been credentialed
as a member of the U.S. Pharmacopeial Convention.
H. N. Shivakumar, PhD, is currently working as professor and head in the Depart-
ment of Pharmaceutics at the KLE University’s College of Pharmacy, Bangalore,
India. Dr. Shivakumar received his doctoral degree in pharmacy from Rajiv Gandhi
xvi Contributors’ Biographies
University of Health Sciences, Bangalore, India. He completed his postdoctoral
research in S. N. Murthy Research Group at the University of Mississippi, University,
Mississippi. His postdoctoral research was focused on passive targeting of micropar-
ticulate systems to the lymphatics for various therapeutic interventions. He was also
involved in developing innovative drug delivery strategies for transdermal and trans-
ungual applications. He holds an appointment as a principal scientist with DermPerm
Research Inc., Bangalore, India. Dr. Shivakumar has around 25 research articles in
peer-reviewed journals and two book chapters to his credit.
Michael M. Tunney, PhD, is a reader of clinical pharmacy in the School of Pharmacy
at Queen’s University Belfast. His research interests are centered on clinical pharmacy
and pharmaceutical microbiology. His current work focuses on the detection and treat-
ment of polymicrobial infection in a range of respiratory diseases including cystic
fibrosis and chronic obstructive pulmonary disease. Other key areas of interest include
treatment of biofilm infection of indwelling implants and determination of the fac-
tors associated with success or failure of methicillin-resistant Staphylococcus aureus
decolonization in hospital inpatients. Dr. Tunney has published more than 50 research
papers and has contributed to a number of microbiology and biomaterials textbooks.
