Transdermal iontophoresis of insulin. Part 1: A study on the issues associated with the use of platinum electrodes on rat skin

Abstract

We have studied the issues associated with the use of platinum electrodes for transdermal iontophoretic delivery of peptides, using insulin as a model peptide. Insulin permeation was studied using full-thickness rat skin by varying the donor solution pH as a function of electrode polarity. The stability of insulin under the iontophoretic conditions was studied using TLC, SDS-polyacrylamide gel electrophoresis and HPLC. Large pH shifts were observed during anodal iontophoresis (AI), when the donor solution pH was above the isoelectric point of insulin and in cathodal iontophoresis (CI), when the donor solution pH was below the isoelectric point of insulin. The direction and magnitude of electroosmotic flow was influenced by pH of the donor solution and the electrode polarity. On the other hand, the buffer used to maintain the pH governed the contribution of electrorepulsion to the overall transport of insulin. Electrochemical degradation of insulin was significant during AI at pH 7.4. Among the pH investigated, AI of insulin at pH 3.6 and CI at pH 8.35 were better, as the pH shift was relatively less and electrochemically more stable during iontophoresis as compared with other pH. In summary, the pH shift caused by platinum electrodes had a significant influence on the permeation and stability of insulin.

Changes of the solution pH due to exposure by high-voltage electric pulses

“…The shift in pH when using iontophoresis for transdermal drug delivery was reported by Kari [25] and Meyer et al [26]. Pillai et al [27] observed the shift of the pH of a donor solution of up to 4-5 pH units during ionthophoresis. Large changes in pH in the vicinity of electrodes (the acidification around the anode and alkanization at the cathode) were also supposed to be the determining factors in the destruction of tissues in electrochemical treatment of tumors [28,29].…”

Proteins and Peptides: Strategies for Delivery to and Across the Skin

“…For example, Boinpally et al 38 reported that the in vitro transport of cyclosporin from lecithin vesicles under anodal iontophoresis was greater than when applied in combination with a microemulsion. Pillai and coworkers [49][50][51][52][53][54][55] have systematically investigated the iontophoretic delivery of insulin with a range of solvents and chemical penetration enhancers. Whilst increased skin penetration could be achieved this was frequently associated with increased skin irritation.…”

A skin permeability model of insulin in the presence of chemical penetration enhancer

“…A review of the available literature for the pertinent data indicates that insulin has been predominantly delivered through the skin using physical methods like iontophoresis (Rao and Misra, 1994, Pillai et al, 2003a, Pillai et al, 2003b, Pillai and Panchagnula, 2003a, Pillai and Panchagnula, 2003b, Pillai et al, 2004a, Pillai et al, 2004b) and sonophoresis (Mitragotri et al, 1996), with very few reported studies on the use of CPEs. Pillai et al and Choi et al (Choi et al, 1999, Pillai and Panchagnula, 2003a, Pillai and Panchagnula, 2003b, Pillai et al, 2004b) have studied the effect of solvents like ethanol, propylene glycol, ethyl acetate and isopropyl myristate on insulin permeation.…”