1: Pharm Res 1997 May;14(5):638-44
Macromolecules as novel transdermal transport enhancers for skin electroporation.
Vanbever R, Prausnitz MR, Preat V
Unite de Pharmacie galenique, Ecole de Pharmacie, Universite catholique
de Louvain, Brussels, Belgium.
PURPOSE: Macromolecules were investigated as chemical enhancers of transdermal
transport by skin electroporation. Although unable to enhance passive or
iontophoretic transport, macromolecules are proposed to enhance electroporation-assisted
delivery by stabilizing the increased permeability caused by high-voltage
pulses. METHODS: To test this hypothesis, we examined the timescale of
transport, the influence of electrical protocol and the influence of macromolecule
size, structure, and charge on enhancement of transdermal mannitol transport
in vitro by heparin, dextran-sulfate, neutral dextran, and poly-lysine.
RESULTS: Skin electroporation increased transdermal mannitol delivery by
approximately two orders of magnitude. The addition of macromolecules further
increased transport up to five-fold, in support of the proposed hypothesis.
Macromolecules present during pulsing enhanced mannitol transport after
pulsing for hours, apparently by a macromolecule-skin interaction. No enhancement
was observed during passive diffusion or low-voltage iontophoresis, suggesting
that macromolecules interact specifically with transport pathways created
at high voltage. Although all macromolecules studied enhanced transport,
those with greater charge and size were more effective.
CONCLUSIONS: This study demonstrates that macromolecules can be used as
transdermal transport enhancers uniquely suited to skin electroporation.
PMID: 9165536, UI: 97308310