Facilitated transdermal delivery of therapeutic peptides and proteins by iontophoretic delivery devices

Abstract

Over the years, extensive research effort has been devoted to the development of noninvasive drug delivery techniques for controlled systemic delivery of therapeutic peptides and proteins through various easily accessible organs/tissues. Iontophoresis has recently been discovered as a potential drug delivery technique for noninvasive, programmed systemic delivery of peptide and protein drugs. Several iontophoretic delivery devices have been developed. In this article, the feasibility of using iontophoretic delivery devices to facilitate the transdermal transport of hydrophilic charged macromolecules of peptides, such as vasopressin and proteins, such as insulin, across the skin (which has the lipophilic stratum corneum as the permeation barrier) is demonstrated. In vitro skin permeation studies and in vivo pharmacokinetic and pharmacodynamic studies in diabetic animals suggested that the systemic bioavailability of peptides and proteins, as well as the pharmacodynamic responses, are dependent upon the electronic variables of the iontophoretic delivery device, e.g. waveform, frequency, on/off ratio and intensity of the current applied, physiochemical parameters, e.g. pH and ionic strength, as well as physiological variables, such as treatment of the stratum corneum. The pharmacokinetics-pharmacodynamics relationship is established and the mechanism of iontophoresis-facilitated transdermal transport of peptide-based macromolecules are analyzed.