Transdermal Iontophoresis : Delivery Control by Ion-Exchange Fibers and Nanocarriers

Kristina Malinovskaja-Gomez

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

Biological variation and poor transport efficacy are the major concerns in the development of novel iontophoretic drug delivery systems for the transdermal administration of therapeutics. One possibility to overcome these limitations would be to load the drug in interest into a reservoir system such as ion-exchange fibers or nanocarriers prior administration. More precise and homogenous control of drug release and the following transdermal iontophoretic permeation could be obtained as the transdermal device/patch would determine the rate of drug transfer instead of the skin, leading to smaller inter- and intrasubject variability. In addition, the range of molecules delivered by iontophoresis can be expanded as charges could be imparted to neutral drugs by encapsulating them in charged drug carriers. Other benefits raising from such combined systems include enhanced drug transport into or across the skin, improved drug stability and decreased local side effects on skin. The aim of this thesis was to study in vitro the applicability of systems that combine iontophoresis and either drug-loaded ion-exchange fibers or nanocarriers for the controlled transdermal delivery of therapeutics. Firstly, drug reservoirs based on cation-exchange fibers were utilized to retard drug release and provide additional control into transdermal transport of a small molecular drug and a peptide. The drug release kinetics could be modified by the choice of the fiber type or the ionic composition of the external solution. The application of pulsed current iontophoresis instead of conventional constant current led to increased transport efficiency of a cationic hydrophobic peptide that has a tendency to adsorb into skin and inhibit electroosmosis as its main transport mechanism. In addition, drug delivery systems combining iontophoresis and nanoencapsulation into polymeric nanoparticles or lipid vesicles for the controlled transdermal delivery of lipophilic or hydrophilic model compound were developed and tested. Although the obtained nanocarriers were considered as suitable for transdermal iontophoretic administration, regarding the colloidal properties, stability and release kinetics, no clear advantage was observed with respect to drug permeation from free drug formulation. Throughout the thesis, the impact of formulation parameters and current type on drug transport efficiency was monitored. Iontophoretic transdermal drug delivery from polymeric nanoparticle-based formulations but not from lipid vesicular nanocarriers was improved by the application of pulsed current. ii In conclusion, binding the drug molecules prior iontophoresis into reservoir based on ion-exchange material or nanocarriers is a promising approach to be utilized in controlled transdermal delivery, although the comprehensive evaluation of full potential of such systems tailored for specific drug warrants further investigation in the future.
Original languageEnglish
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-2441-8
Electronic ISBNs978-951-51-2442-5
Publication statusPublished - 2016
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • 317 Pharmacy

Cite this

Malinovskaja-Gomez, K. (2016). Transdermal Iontophoresis : Delivery Control by Ion-Exchange Fibers and Nanocarriers. Helsinki: University of Helsinki.
Malinovskaja-Gomez, Kristina. / Transdermal Iontophoresis : Delivery Control by Ion-Exchange Fibers and Nanocarriers. Helsinki : University of Helsinki, 2016. 76 p.
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title = "Transdermal Iontophoresis : Delivery Control by Ion-Exchange Fibers and Nanocarriers",
abstract = "Biological variation and poor transport efficacy are the major concerns in the development of novel iontophoretic drug delivery systems for the transdermal administration of therapeutics. One possibility to overcome these limitations would be to load the drug in interest into a reservoir system such as ion-exchange fibers or nanocarriers prior administration. More precise and homogenous control of drug release and the following transdermal iontophoretic permeation could be obtained as the transdermal device/patch would determine the rate of drug transfer instead of the skin, leading to smaller inter- and intrasubject variability. In addition, the range of molecules delivered by iontophoresis can be expanded as charges could be imparted to neutral drugs by encapsulating them in charged drug carriers. Other benefits raising from such combined systems include enhanced drug transport into or across the skin, improved drug stability and decreased local side effects on skin. The aim of this thesis was to study in vitro the applicability of systems that combine iontophoresis and either drug-loaded ion-exchange fibers or nanocarriers for the controlled transdermal delivery of therapeutics. Firstly, drug reservoirs based on cation-exchange fibers were utilized to retard drug release and provide additional control into transdermal transport of a small molecular drug and a peptide. The drug release kinetics could be modified by the choice of the fiber type or the ionic composition of the external solution. The application of pulsed current iontophoresis instead of conventional constant current led to increased transport efficiency of a cationic hydrophobic peptide that has a tendency to adsorb into skin and inhibit electroosmosis as its main transport mechanism. In addition, drug delivery systems combining iontophoresis and nanoencapsulation into polymeric nanoparticles or lipid vesicles for the controlled transdermal delivery of lipophilic or hydrophilic model compound were developed and tested. Although the obtained nanocarriers were considered as suitable for transdermal iontophoretic administration, regarding the colloidal properties, stability and release kinetics, no clear advantage was observed with respect to drug permeation from free drug formulation. Throughout the thesis, the impact of formulation parameters and current type on drug transport efficiency was monitored. Iontophoretic transdermal drug delivery from polymeric nanoparticle-based formulations but not from lipid vesicular nanocarriers was improved by the application of pulsed current. ii In conclusion, binding the drug molecules prior iontophoresis into reservoir based on ion-exchange material or nanocarriers is a promising approach to be utilized in controlled transdermal delivery, although the comprehensive evaluation of full potential of such systems tailored for specific drug warrants further investigation in the future.",
keywords = "Administration, Cutaneous, Apomorphine, +administration & dosage, Cation Exchange Resins, Drug Carriers, +chemistry, Drug Delivery Systems, +methods, Flufenamic Acid, Ion Exchange, Iontophoresis, In Vitro Techniques, Leuprolide, Liposomes, Nanoparticles, Nanotechnology, Pharmaceutical Preparations, Skin, +metabolism, Skin Absorption, Surface Properties, 317 Pharmacy",
author = "Kristina Malinovskaja-Gomez",
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year = "2016",
language = "English",
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Transdermal Iontophoresis : Delivery Control by Ion-Exchange Fibers and Nanocarriers. / Malinovskaja-Gomez, Kristina.

Helsinki : University of Helsinki, 2016. 76 p.

Research output: ThesisDoctoral ThesisCollection of Articles

TY - THES

T1 - Transdermal Iontophoresis : Delivery Control by Ion-Exchange Fibers and Nanocarriers

AU - Malinovskaja-Gomez, Kristina

N1 - M1 - 76 s. + liitteet Helsingin yliopisto Volume: Proceeding volume:

PY - 2016

Y1 - 2016

N2 - Biological variation and poor transport efficacy are the major concerns in the development of novel iontophoretic drug delivery systems for the transdermal administration of therapeutics. One possibility to overcome these limitations would be to load the drug in interest into a reservoir system such as ion-exchange fibers or nanocarriers prior administration. More precise and homogenous control of drug release and the following transdermal iontophoretic permeation could be obtained as the transdermal device/patch would determine the rate of drug transfer instead of the skin, leading to smaller inter- and intrasubject variability. In addition, the range of molecules delivered by iontophoresis can be expanded as charges could be imparted to neutral drugs by encapsulating them in charged drug carriers. Other benefits raising from such combined systems include enhanced drug transport into or across the skin, improved drug stability and decreased local side effects on skin. The aim of this thesis was to study in vitro the applicability of systems that combine iontophoresis and either drug-loaded ion-exchange fibers or nanocarriers for the controlled transdermal delivery of therapeutics. Firstly, drug reservoirs based on cation-exchange fibers were utilized to retard drug release and provide additional control into transdermal transport of a small molecular drug and a peptide. The drug release kinetics could be modified by the choice of the fiber type or the ionic composition of the external solution. The application of pulsed current iontophoresis instead of conventional constant current led to increased transport efficiency of a cationic hydrophobic peptide that has a tendency to adsorb into skin and inhibit electroosmosis as its main transport mechanism. In addition, drug delivery systems combining iontophoresis and nanoencapsulation into polymeric nanoparticles or lipid vesicles for the controlled transdermal delivery of lipophilic or hydrophilic model compound were developed and tested. Although the obtained nanocarriers were considered as suitable for transdermal iontophoretic administration, regarding the colloidal properties, stability and release kinetics, no clear advantage was observed with respect to drug permeation from free drug formulation. Throughout the thesis, the impact of formulation parameters and current type on drug transport efficiency was monitored. Iontophoretic transdermal drug delivery from polymeric nanoparticle-based formulations but not from lipid vesicular nanocarriers was improved by the application of pulsed current. ii In conclusion, binding the drug molecules prior iontophoresis into reservoir based on ion-exchange material or nanocarriers is a promising approach to be utilized in controlled transdermal delivery, although the comprehensive evaluation of full potential of such systems tailored for specific drug warrants further investigation in the future.

AB - Biological variation and poor transport efficacy are the major concerns in the development of novel iontophoretic drug delivery systems for the transdermal administration of therapeutics. One possibility to overcome these limitations would be to load the drug in interest into a reservoir system such as ion-exchange fibers or nanocarriers prior administration. More precise and homogenous control of drug release and the following transdermal iontophoretic permeation could be obtained as the transdermal device/patch would determine the rate of drug transfer instead of the skin, leading to smaller inter- and intrasubject variability. In addition, the range of molecules delivered by iontophoresis can be expanded as charges could be imparted to neutral drugs by encapsulating them in charged drug carriers. Other benefits raising from such combined systems include enhanced drug transport into or across the skin, improved drug stability and decreased local side effects on skin. The aim of this thesis was to study in vitro the applicability of systems that combine iontophoresis and either drug-loaded ion-exchange fibers or nanocarriers for the controlled transdermal delivery of therapeutics. Firstly, drug reservoirs based on cation-exchange fibers were utilized to retard drug release and provide additional control into transdermal transport of a small molecular drug and a peptide. The drug release kinetics could be modified by the choice of the fiber type or the ionic composition of the external solution. The application of pulsed current iontophoresis instead of conventional constant current led to increased transport efficiency of a cationic hydrophobic peptide that has a tendency to adsorb into skin and inhibit electroosmosis as its main transport mechanism. In addition, drug delivery systems combining iontophoresis and nanoencapsulation into polymeric nanoparticles or lipid vesicles for the controlled transdermal delivery of lipophilic or hydrophilic model compound were developed and tested. Although the obtained nanocarriers were considered as suitable for transdermal iontophoretic administration, regarding the colloidal properties, stability and release kinetics, no clear advantage was observed with respect to drug permeation from free drug formulation. Throughout the thesis, the impact of formulation parameters and current type on drug transport efficiency was monitored. Iontophoretic transdermal drug delivery from polymeric nanoparticle-based formulations but not from lipid vesicular nanocarriers was improved by the application of pulsed current. ii In conclusion, binding the drug molecules prior iontophoresis into reservoir based on ion-exchange material or nanocarriers is a promising approach to be utilized in controlled transdermal delivery, although the comprehensive evaluation of full potential of such systems tailored for specific drug warrants further investigation in the future.

KW - Administration, Cutaneous

KW - Apomorphine

KW - +administration & dosage

KW - Cation Exchange Resins

KW - Drug Carriers

KW - +chemistry

KW - Drug Delivery Systems

KW - +methods

KW - Flufenamic Acid

KW - Ion Exchange

KW - Iontophoresis

KW - In Vitro Techniques

KW - Leuprolide

KW - Liposomes

KW - Nanoparticles

KW - Nanotechnology

KW - Pharmaceutical Preparations

KW - Skin

KW - +metabolism

KW - Skin Absorption

KW - Surface Properties

KW - 317 Pharmacy

M3 - Doctoral Thesis

SN - 978-951-51-2441-8

T3 - Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis

PB - University of Helsinki

CY - Helsinki

ER -

Malinovskaja-Gomez K. Transdermal Iontophoresis : Delivery Control by Ion-Exchange Fibers and Nanocarriers. Helsinki: University of Helsinki, 2016. 76 p. (Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis; 61/2016).