Abstract：
The transdermal delivery of naloxone for opioid overdose emergency purposes is a challenge due to its poor rate of diffusion through the layers of skin. This results in delayed delivery of an insufficient amount of the drug within minimal time as is desired to save lives. The ability of dissolving polymeric microneedles to shorten the lag time significantly has been explored and shown to have prospects in terms of the transdermal delivery of naloxone. This is an option that offers critical advantages to the ongoing opioid crisis, including ease of distribution and easy administration, with little to no need for intervention by clinicians. Nonetheless, this approach by itself needs augmentation to meet pharmacokinetic delivery attributes desired for a viable clinical alternative to existing market dosage forms. In this study, we report the success of an optimized iontophoresis-coupled naloxone loaded dissolving microneedle patch which had facilitated a 12- fold increase in average cumulative permeation and a 6-fold increase in drug flux over a conventional dissolving microneedle patch within 60 min of application (p < 0.05). This translates to a 30 % decrease in dose requirement in a mechanistically predicted microneedle patch established to be able to achieve the desired early plasma concentration time profile needed in an opioid overdose emergency. Applying a predictive mathematical model, we describe an iontophoresis-coupled microneedle patch design capable of meeting the desired pharmacokinetic profile for a viable naloxone delivery form through skin.
摘要：
用于阿片类药物过量紧急目的的纳洛酮的透皮递送是一个挑战,因为其通过皮肤层的扩散速率差。这导致在最短的时间内延迟递送不足量的药物,这是挽救生命所需的。已经探索了溶解聚合物微针以显著缩短滞后时间的能力,并且显示出在纳洛酮的透皮递送方面具有前景。这是一个为持续的阿片类药物危机提供关键优势的选择，包括易于分发和易于管理，几乎不需要临床医生的干预。尽管如此，这种方法本身需要增强,以满足现有市场剂型的可行临床替代方案所需的药代动力学递送属性.在这项研究中,我们报道了一种优化的离子电渗疗法偶联的纳洛酮溶解型微针贴剂的成功应用,该贴剂在应用后60分钟内,与常规溶解型微针贴剂相比,平均累积渗透率增加12倍,药物通量增加6倍(p<0.05).这转化为机械预测的微针贴片中的剂量需求减少30%,所述微针贴片建立为能够实现阿片类药物过量紧急情况中所需的期望的早期血浆浓度时间曲线。应用预测数学模型，我们描述了离子电渗偶联的微针贴片设计，能够满足通过皮肤的可行纳洛酮递送形式所需的药代动力学特征。
