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Current status and future potential of transdermal drug delivery

Nature Reviews Drug Discovery volume 3, pages 115124 (2004) | Download Citation

Subjects

Abstract

The past twenty five years have seen an explosion in the creation and discovery of new medicinal agents. Related innovations in drug delivery systems have not only enabled the successful implementation of many of these novel pharmaceuticals, but have also permitted the development of new medical treatments with existing drugs. The creation of transdermal delivery systems has been one of the most important of these innovations, offering a number of advantages over the oral route. In this article, we discuss the already significant impact this field has made on the administration of various pharmaceuticals; explore limitations of the current technology; and discuss methods under exploration for overcoming these limitations and the challenges ahead.

Key points

  • Transdermal delivery of drugs, proteins and other bioactive molecules is an attractive alternative for compounds that cannot be administered orally due to degradation in the gastrointestinal tract and liver. As a result, transdermal patches exist in the United States to administer twelve different drugs or drug combinations to treat a variety of indications.

  • Although it would be beneficial to deliver more drugs from patches, the skin's outer layer of stratum corneum provides a barrier to transport that prevents transdermal delivery of most compounds at therapeutic levels. A broad variety of chemical enhancers has been used to increase drug penetration across skin, but their efficacy has been limited by associated skin irritation and toxicity.

  • Electrical and acoustical energy have been used to increase transdermal delivery. Iontophoresis, involving increased transport across skin mediated primarily by electrophoretic migration, is used in a few FDA-approved products and is poised to have increased impact. Additional research has shown that short, high-voltage pulses causing electroporation can increase transdermal transport not only by electrophoretic movement, but also through short-lived nanometre pores created within the skin. Also of commercial interest, ultrasound and acoustic shock waves have been shown to increase skin permeability by a mechanism believed to involve transient disruption of skin nanostructure.

  • Skin can also be disrupted on the micron scale to increase permeability. Arrays of microscopic needles inserted painlessly into skin have been shown to increase skin permeability for the delivery of small drugs, macromolecules and microparticles, which has stimulated increasing industrial activity. Jet injectors, thermal ablation methods and very small hypodermic needles are also the subject of renewed and on-going commercial interest.

  • After an initial period of development that led to passive systems like the nicotine patch, transdermal drug delivery is experiencing a resurgence of activity using active enhancement methods base on nano- and micro-scale disruption of skin structure. Synergistic combinations of these methods could provide still better results.

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Acknowledgements

We thank R. Gale for helpful discussions. This work was supported in part by National Institutes of Health grants.

Author information

Affiliations

  1. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.  mark.prausnitz@chbe.gatech.edu

    • Mark R. Prausnitz
  2. Department of Chemical Engineering, University of California, Santa Barbara, California 93106, USA.  samir@engineering.ucsb.edu

    • Samir Mitragotri
  3. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.  rlanger@mit.edu

    • Robert Langer

Authors

  1. Search for Mark R. Prausnitz in:

  2. Search for Samir Mitragotri in:

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Competing interests

M.R.P. owns shares in BioValve Technologies. S.M. owns shares and is an advisor or consultant to Sontra Medical Corp. and fqubed. R.L. owns shares and is an advisor to Sontra Medical Corp. and TransForm Pharmaceuticals. All authors are inventors on patents on the subject of transdermal delivery that are owned by their current or former academic or industrial employers.

Glossary

TRANSDERMAL DELIVERY

The movement of compounds across the stratum corneum and into systemic circulation.

STRATUM CORNEUM

The outer layer of epidermis, consisting of several layers of corneocytes in a lipid-rich matrix.

EPIDERMIS

The outer, epithelial portion of the skin.

CORNEOCYTE

The non-living, keratin-filled squamous cell of the stratum corneum.

DESQUAMATED

Shed from the surface of the skin.

SURFACTANT

A molecule typically containing separate hydrophilic and hydrophobic domains that reduces surface tension of water.

OLEIC ACID

A carboxylic acid with a linear chain of 18 carbon atoms and one double bond (C18H34O2).

TOPICAL DELIVERY

The movement of compounds across the stratum corneum and locally into the skin.

IONTOPHORESIS

The movement of molecules across the skin or other tissue under the influence of an electric field.

HYPERHIDROSIS

Excessive sweating, especially of the hands and feet.

ELECTROPHORESIS

The migration of molecules with a net charge under the influence of an electric field.

ELECTRO-OSMOSIS

The movement in an electric field of liquid within a porous medium having a fixed net charge.

ELECTROPORATION

The formation of aqueous pathways across a lipid bilayer by a pulsed electric field.

ULTRASOUND

A sound (that is, pressure) wave at a frequency greater than 20 kHz.

SONOPHORESIS

The movement of molecules across the skin or other tissue under the influence of an acoustic field.

CAVITATION

The formation of gaseous bubbles within a liquid by ultrasound or other mechanical forces.

MICRONEEDLE

A needle of micrometre dimensions usually fabricated using techniques derived from the microelectronics industry.

LANGERHANS' CELL

Dendritic clear cells in the epidermis believed to be antigen fixing and processing cells of monocytic origin.

THERMAL PORATION

The formation of aqueous pathways across stratum corneum by the application of pulsed heat.

JET INJECTION

The high-velocity penetration into or across the skin of liquid droplets (or solid particles) often containing a drug.

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