Transdermal iontophoretic delivery of bovine insulin and monomeric human insulin analogue

J Control Release. 1999 May 1;59(1):99-105. doi: 10.1016/s0168-3659(98)00184-9.

Abstract

The present study was undertaken to explore the possibility of delivering bovine insulin in streptozocin (STZ)-induced diabetic rats by iontophoresis. Further, the effect of iontophoresis of monomeric human insulin analogue (r-DNA origin) on the plasma glucose level (PGL) of diabetic rats was studied. Iontophoresis of bovine insulin (10-200 IU/ml) was not effective in decreasing the PGL in untreated diabetic rats. Pretreatment of skin with oleic acid or menthol for 3 h followed by iontophoresis of bovine insulin also failed to produce a fall in PGL. Application of a depilatory cream for hair removal (24 h before the experiment), followed by iontophoresis of bovine insulin (10, 30 and 100 IU/ml) produced a concentration-dependent fall in PGL. Further, application of depilatory cream immediately before the experiment produced a substantial fall in PGL both by passive diffusion and iontophoresis. Depilatory cream might have drastically reduced the barrier function of skin such that conventional bovine insulin (dimer and hexamer) penetrates through the intact skin by iontophoresis and even by passive diffusion. Depilatory cream or the active components of depilatory cream may be useful as penetration enhancers for transdermal delivery of drugs especially macromolecules such as insulin. Iontophoresis of monomeric human insulin analogue (B9 Asp, B27 Glu) through intact skin (untreated) produced a significant fall in PGL in diabetic rats. Monomeric human insulin analogues which have low tendency to self aggregation may be promising candidates for the transdermal iontophoretic delivery of insulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Cattle
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diffusion
  • Female
  • Hair Removal
  • Humans
  • Insulin / administration & dosage*
  • Insulin / analogs & derivatives*
  • Insulin / pharmacokinetics
  • Iontophoresis / methods*
  • Male
  • Rats
  • Rats, Wistar
  • Skin / drug effects
  • Skin / metabolism
  • Skin Absorption / drug effects
  • Skin Absorption / physiology*

Substances

  • Insulin