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Effect of current profile on the stability and transdermal iontophoretic delivery of lhrh and nafarelin in vitro

机译:电流谱对lhrh和那法瑞林体外稳定性和透皮离子电渗传递的影响

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Transdermal iontophoresis is a potential method to administer therapeutically actigve peptides into the systemic circulation because most peptides are ineffective when taken orally~1. Especially the stability and biological activity of peptides are a concern. In this study, stability and iontophoretic transdermal permeation of two decapeptides, luteinizing hormone releasing hormone (LHRH) and Nafarelin, were evalauted. Nafarelin is an agonist analogue of LHRH: the sixth amino acid of LHRH, glycine, is replaced by D-naphthylalanine that makes the molecule more lipophilic and biologically more active.~2 The aim of this study was to evalaute the stability of LHRH and Nafarelin in buffer solution, with electrical current, and in the presence of skin metabolizing enzymes. The effect of different current profiles - direct current (DC), pulsed DC with different on/off ratios, and alternating current (AC) with differnet +/- duty cycles - on the trandermal iontophoresis of these peptides was measued. The influence of the peptides and current profile on the permeation of neutrla sugar, mannitol, during the iontophoresis was also determined.
机译:透皮离子电渗疗法是将治疗活性的肽施用到体循环中的一种潜在方法,因为大多数肽在口服时无效[1]。尤其是肽的稳定性和生物学活性是一个问题。在这项研究中,评估了黄体生成激素释放激素(LHRH)和那法瑞林这两种十肽的稳定性和离子电渗透皮渗透性。 Nafarelin是LHRH的激动剂类似物:LHRH的第六个氨基酸甘氨酸被D-萘丙氨酸取代,使该分子更具亲脂性,并且生物学活性更高。〜2本研究的目的是评估LHRH和Nafarelin的稳定性。在缓冲溶液中,通电,并存在皮肤代谢酶。测量了不同电流分布图-直流电(DC),具有不同开/关比的脉冲DC和具有不同净+/-占空比的交流电(AC)-对这些肽的透皮离子电渗疗法的影响。还确定了肽和电流谱对离子电渗过程中中性糖,甘露醇渗透的影响。

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