PubMed · 13149861
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E M DUNLOP. 1954. Multiple peripheral neuritis.. https://doi.org/10.1136/sti.30.1.44
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Electronically facilitated transdermal delivery of human parathyroid hormone (1-34), hPTH (1-34), was investigated in vitro, using dermatomed porcine skin. The effect of iontophoretic current density, electroporative pulse voltages and also electroporation followed by iontophoresis was investigated on the in vitro percutaneous absorption of hPTH (1-34). Iontophoresis at 0.5 mA/cm2 current density significantly enhanced (P<0.05) the flux of hPTH (1-34) in comparison to passive flux. Electroporation pulses of 100, 200 and 300 V significantly increased (P<0.05) the flux of hPTH (1-34) in comparison with the passive as well as iontophoretic flux at 0.5 mA/cm2. The electroporative flux of hPTH (1-34) was found to vary linearly (R2 = 0.97) with the pulse amplitude. The principal barrier of the skin, stratum corneum, was found perturbed following the pulses as evident by light microscopy studies. The application of electroporation pulses followed by iontophoresis further increased the flux by several fold. The flux of hPTH (1-34) with the electroporation pulses of 100 and 300 V followed by iontophoresis at 0.2 mA/cm2 was 10- and 5-fold higher, respectively, in comparison to the flux with corresponding pulses alone. This shows the synergistic effect of iontophoresis in combination with electroporation on skin permeability of hPTH (1-34). The results indicate the possibility of designing controlled transdermal delivery systems for hPTH (1-34) using electroporation followed by iontophoresis.
The skin forms a barrier to the external environment, maintaining body fluids within our system and excluding harmful substances, while the skin is a site of administration of drugs for topical and systemic chemotherapy. It is an important issue to predict the rate at which drugs or other xenobiotics penetrate the skin. In this article, we review modeling approaches for predicting skin permeation of compounds, including both mechanistic and empirical approaches. Mechanistic approaches can give us much information on understanding of skin permeation of the compounds, such as structure-permeability relationship, contribution of each barrier step, mechanism of penetration enhancers, and in vivo-in vitro relationship. On the other hand, empirical modeling can overcome any inaccuracies of mechanistic models caused by the existence of uncertainties and, therefore, give us better predictions from the practical point of view. Artificial neural networks are being available for empirical modeling of complex skin transport phenomenon.
BACKGROUND: Nitrates are widely used to treat coronary artery disease, but their therapeutic value is compromised by the rapid development of tolerance. Recently, the renin-angiotensin system has been suggested to play an important role in the development of nitrate tolerance. METHODS AND RESULTS: Sixty-four patients with coronary spastic angina were investigated to clarify the effect of angiotensin II type 1 receptor blocker (ARB) therapy on nitrate tolerance. Transdermal nitroglycerin (10 mg/d) and an ARB (candesartan, 8 mg/d) were administered to 21 patients (GTN+ARB group) for 3 days, whereas transdermal nitroglycerin and placebo were administered to 19 patients (GTN group). Another 18 patients were treated with placebo skin patches and placebo tablets for 3 days (control group). The brachial artery response to incremental doses of intravenous nitroglycerin (0.01, 0.1, and 1.0 micro;g/kg) was measured by ultrasound before and after transdermal nitroglycerin therapy. Before treatment, the arterial diameter was increased by nitroglycerin injection in each group. After treatment, the increase of arterial diameter was significantly suppressed in the GTN group but not in the control or GTN+ARB groups. The plasma level of thioredoxin (a marker of oxidative stress) was increased in the GTN group after treatment (P<0.01) but not in the control or GTN+ARB groups. CONCLUSIONS: An ARB suppressed the development of nitrate tolerance during transdermal nitroglycerin therapy. These results suggest that increased oxidative stress induced by activation of angiotensin II may play an important role in the development of nitrate tolerance.