Enhanced Insulin Transport Through Skin By High-Voltage Pulse

Diabetes is a life-long disease marked by high levels of sugar in the blood. It can be caused by too little insulin (a hormone produced by the pancreas to regulate blood sugar), resistance to insulin, or both. In recent years, the incidence and prevalence of diabetes has significantly increased. Insulin remains the most effective drug for a diabetic patient to control their blood glucose levels. The route for insulin delivery is restricted to subcutaneous injections, as opposed to the oral route, due to insulin inactivation by proteolytic enzymes in the gastrointestinal tract and low permeability through the intestinal membrane. However, the subcutaneous injection of insulin has various disadvantages such as hyperinsulinemia, pain, allergic reactions and low patient compliance.Obviously, from this perspective, the development of other delivery system for insulin would be most important. To date, various strategies have been developed to try and achieve appropriate, safe, and effective delivery system, including oral administration, inhaled administration, transdermal administration and so on.Transdermal drug delivery (TDD) is that patching the drug on the skin, the drug molecules permeate through the skin into the subcutaneous capillary vessels. This method can avoid the "the first pass " in the liver of degradation of enzymes in the gastrointestinal tract for oral use as well as the difficult maintenance in blood concentration of the drug for infection. However, the molecular weight of insulin is large (5700Da);it can hardly permeate the skin. In order to solve this problem, several physical and chemical methods, such as iontophoresis, electroporation, photomechanical wave, sonophoresis, microneedles and chemical enhancers, are applied to improve the permeability of skin. In this paper, we use high pulse electroporation to promote the insulin's transport through epidermis.In this research, we mainly study the two aspects: the change of insulin permeation flux caused by electroporation pulse and the change of the skin resistance during the pulse period.1. Insulin permeation flux under electroporation pulse: applied the pulse voltage to the both side of the skin, then measured the concentration of insulin in the receptor room in different sampling times, so that we can calculate the flux of the insulin which transport through the skin. The results show that, in the different pulse protocol, the permeation flux of insulin is not achieving the maximum as soon as the pulse applied. However, it will be the maximum after 0.5-1 hours. After that it will decrease along with the time.2. The affection of pulse voltage and the energy to insulin transdermal permeation flux: Experiment dates indicate that, in the same capacitance, the insulin permeation flux increase when the voltage increases. According to the previous studies, we know that the energy of the pulse is very important to the permeation flux. In our experiment, the insulin flux is the same when the energy is same, no matter what the protocol is. In certain energy range, the flux is increased with the increased energy.3. Resistance of skin in electrical pulse: Results show;(1) We obtained that resistance of across epidermis decreased along with initial voltage of pulse increased using logarithm trend line fitting;(2) in same pulse period, voltage decreased with time expand but resistance of across stratum corneum increased.