Electroporation pulsing protocols

The objective of these IPPSF studies was to assess the effect of electroporation on the iontophoretic delivery of LHRH. The experimental design and Porex electrodes have been fully described elsewhere (Heit et al, 1993 1994 Monteiro-Riviere, 1990). Briefly, a 1.0-mg/ml solution of LHRH in lOmM 2-(A-morpholino)ethanesulfonic acid buffer with 154mM NaCl was placed in A.5-cm Ag/AgCl electrodes. Direct current (positive polarity, anode in the donor) was applied at a current density of0.4mA/cm2 for 30min. The venous effluent of the IPPSF was collected and assayed for LHRH using a radioimmunoassay. An electroporative pulse of 500 V and 5-msec exponential time constant was applied immediately prior to iontophoresis. In some experiments, the electroporation/iontophoresis protocol was repeated for various intervals to assess the effect of repeated applications. 

Jadoul and Preat [56] have also proposed a similar explanation for the lack of synergistic effects on transdermal delivery of domperidone with combined electroporation (1 pulse of 1000 V with a time constant of 4 ms) and iontophoresis (0.4 mA/cm2) despite the fact that iontophoresis was switched on within a few seconds after electroporation. Combined pulsing and iontophoresis also did not improve penetration of sodium nonivamide acetate through nude mouse skin [51], Therefore, when combing the two protocols, it should be more efficient to use a system that delivers current during or immediately after pulsing without delay. 

FIGURE 17.2 Enhancement ratios of total amount of estradiol penetrated and skin deposition from ultradeformable liposomes after an electroporation protocol (5 pulses of 100 V, 100 ms, and 1 min spacing) relative to passive diffusion from the vesicles. 

A major factor in the clinical acceptability of electrically enhanced transdermal delivery is its effect on the skin. The pig is a widely accepted animal model for assessing electrically assisted transdermal delivery (Mon-teiro-Riviere, 1990 Riviere and Monteiro-Riviere, 1991). Preliminaiy studies using electroporation (Riviere et al, 1995) conducted with pigs had two objectives. The first was to identify any unique skin changes associated with electroporation and to determine the effect of pulses on iontophoresis-induced irritation. The second objective was to define a pulse/iontophoresis protocol for drug delivery that was minimally irritating. 

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