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Advanced Drug Delivery Reviews 35 (1999) 1–2
Preface
Enhanced drug delivery using high-voltage pulses
a ,
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b ,*
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Veronique Preat , Mark R. Prausnitz
aDepartment of Pharmaceutical Technology, School of Pharmacy, Catholic University of Louvain, 1200 Brussels, Belgium
bSchools of Chemical Engineering and Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0100, USA
Successful delivery of drugs into the body and to without loss of viability. Electroporation-mediated target tissues and cells inside is limited largely by drug delivery can provide a way to increase drug and slow transport across biological barriers, mostly in gene transport across these biological barriers which the form of lipid bilayer membranes. Although limit transdermal and targeted delivery.
transdermal drug delivery has found success for a One promising application of tissue electropora- handful of small compounds, the poorly-permeable tion is transdermal drug delivery, which is believed lipid bilayers in skin’s stratum corneum prevent to involve transient disruption of lipid bilayer struc- therapeutic delivery of most drugs, especially macro- ture within the skin’s stratum corneum. Application molecules. Similarly, targeted delivery of drugs to of high-voltage pulses to the skin has been shown to tissues (e.g., tumors) and into cells (e.g., for gene increase transdermal drug delivery by several orders therapy) is blocked by lipid bilayer cell membranes. of magnitude, both in vitro and in vivo. Controlled Drugs and genes which could selectively cross cell rates of delivery can be achieved by modifying membranes could be targeted to cells and tissues of electrical parameters and drug formulation. Ex-
interest. perimental data suggest that skin electroporation
Application of short, high-voltage pulses provides could provide a drug delivery method that is both a way to reversibly disrupt lipid bilayer membranes, safe and effective.
thereby creating pathways to deliver molecules ac- Another promising application of tissue electropo- ross cell membranes, into tissues and through the ration is electrochemotherapy. It consists of applying skin by a mechanism commonly called electropora- high-voltage pulses to permeabilize tumor cells to a tion. By briefly inducing a transmembrane voltage of non-permeant drug (e.g., bleomycin). In this way, a few hundred millivolts, lipid bilayers are known to only cells exposed to high-voltage pulses take up become permeable within microseconds and then sufficient drug to be affected. Using this targeting reseal within seconds to minutes. As a well known mechanism, skin, liver and other tumors have been method for laboratory DNA transfection of cells, eradicated in animal models and recent clinical electroporation has recently been applied to tissues studies show promising results. By a similar method, and shown to reversibly permeabilize them, often in vivo gene therapy has been demonstrated using high-voltage pulses to different tissues in animals.
This issue of Advanced Drug Delivery Reviews
*Corresponding authors. Preat: Tel.: (32-2)-764-73-20; fax:´
summarizes the current status of high-voltage pulsing
(32-2)-764-73-98; e-mail: preat@farg.ucl.ac.be. Prausnitz:
for drug delivery applications. After an introductory
Tel.: (404)-894-5135; fax: (404)-894-2866; e-mail:
mark.prausnitz@che.gatech.edu paper on cell electroporation, a series of papers
0169-409X / 99 / $ – see front matter 1999 Elsevier Science B.V. All rights reserved.
P I I : S 0 1 6 9 - 4 0 9 X ( 9 8 ) 0 0 0 5 9 - 3
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2 V. Preat, M.R. Prausnitz / Advanced Drug Delivery Reviews 35 (1999) 1 –2
discuss theoretical and experimental studies of skin and gene delivery. Combined, these studies indicate electroporation, including mechanistic, delivery and that high-voltage pulsing can be an effective way to safety issues. The final papers address electropora- increase lipid bilayer permeability and thereby en- tion of tissues for enhanced cancer chemotherapy hance and target delivery of drugs and genes.
