Transdermal delivery of heparin by skin electroporation.
Prausnitz MR; Edelman ER; Gimm JA; Langer R; Weaver JC Biotechnology (N Y) (AL1), 1995 Nov; 13 (11): 1205-9
Therapeutic uses of compounds produced by biotechnology are
presently limited by the lack of noninvasive methods for
continuous administration of biologically-active
macromolecules. Transdermal delivery would be an attractive
solution, except macromolecules have not previously been
delivered clinically across human skin at therapeutic rates.
To increase transport of a highly-charged macromolecule
(heparin), high-voltage pulses believed to cause
electroporation were applied to skin. Using this approach,
transdermal heparin transport across human skin in vitro
occurred at therapeutic rates (100-500 micrograms/cm2h),
reported to be sufficient for systemic anticoagulation. In
contrast, fluxes caused by low-voltage iontophoresis having
the same time-averaged current were an order of magnitude
lower. Heparin transported across the skin was biologically
active, but with only one eighth the anticoagulant activity
of heparin in the donor compartment due to preferential
transport of small (less active) heparin molecules. Flux,
activity, and transport number data together suggest that
high-voltage pulsing creates transient changes in skin
microstructure which do not occur during iontophoresis.
Safety issues are discussed.