PubMed · 9105760
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M P Dubé, P N Heseltine, M G Rinaldi. 1997. Nystatin prophylaxis.. https://doi.org/10.1128/cmr.10.2.368
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The element vanadium can have insulin mimetic properties and therefore has been suggested as a possible therapeutic agent for treatment of diabetes. A series of peroxovanadium compounds that are more potent at lowering blood glucose levels than sodium metavanadate, sodium orthovanadate and vanadyl sulfate have recently been synthesized. These compounds probably will not be orally active so transdermal administration is a potential option. A patch containing either the peroxovanadium compound [VO(O2)2 1-10 phenanthroline], abbreviated bpV(phen), or placebo was placed on the back of streptozotocin induced diabetic rats and was delivered either passively (16 h) or iontophoretically (0.5 mA/cm2 for 4 h). Blood samples were analyzed for glucose and vanadium levels. Mean blood glucose levels were 83+/-1% and 109+/-1% of the starting values for animals iontophoretically treated with bpV(phen) and vehicle, respectively. The compound's insulin mimetic properties were evident within 60 min of current initiation. Blood glucose levels were reduced to 74+/-14% of the original level after 16 h of passive treatment. The compound was ineffective when fed to animals. Transdermal delivery of bpV(phen) resulted in significantly greater blood levels of vanadium than the orally delivered compound (P<0.05). Overall these experiments demonstrate that peroxovanadium delivered through the skin can lower blood glucose levels in rats. Further experiments are warranted to better characterize the nature of the response and to determine the potential for using these compounds in humans.
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.
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