Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN, USA.
Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN, USA.
Int J Pharm. 2021 Jul 15;604:120739. doi: 10.1016/j.ijpharm.2021.120739. Epub 2021 May 26.
Naloxone (NAL) is administered parenterally or intranasally for treating opioid overdose. The short duration of action of NAL calls for frequent re-dosing which may be eliminated by the development of a transdermal system. This study aimed to assess the effect of microneedles on improving the skin permeation of NAL hydrochloride. In vitro permeation of NAL across intact and microneedle-treated (Dr. Pen™ Ultima A6) porcine skin was evaluated. The effect of microneedle length and application duration, and donor concentration on NAL permeation were investigated. In-vitro in-vivo correlation of the permeation results was done to predict the plasma concentration kinetics of NAL in patients. In vitro passive permeation of NAL after 6 h was observed to be 8.25±1.06 µg/cm. A 56- and 37-fold enhancement was observed with 500 and 250 µm needles applied for 1 min, respectively. Application of 500 µm MNs for 2 min significantly reduced the lag time to ~ 8 min and increasing the donor concentration for the same treatment group doubled the permeation (p < 0.05). Modeling simulations demonstrated the attainment of pharmacokinetic profile of NAL comparable to those obtained with the FDA-approved intramuscular and intranasal devices. Microneedle-mediated transdermal delivery holds potential for rapid and sustained NAL delivery for opioid overdose treatment.
纳洛酮（NAL）经肠胃外或鼻内给药，用于治疗阿片类药物过量。NAL 的作用持续时间短，需要频繁重新给药，这可以通过开发透皮系统来消除。本研究旨在评估微针在改善盐酸纳洛酮皮肤渗透方面的作用。评估了 NAL 盐酸盐在完整和微针处理（Dr. Pen™ Ultima A6）猪皮中的体外渗透。研究了微针长度和应用持续时间以及供体浓度对 NAL 渗透的影响。对渗透结果进行了体内外相关性研究，以预测患者体内 NAL 的血浆浓度动力学。观察到 NAL 在 6 小时后的体外被动渗透为 8.25±1.06µg/cm。分别应用 500µm 和 250µm 针 1 分钟，渗透增强分别为 56 倍和 37 倍。500µm MN 应用 2 分钟可显著降低滞后时间至约 8 分钟，而对于相同的治疗组，增加供体浓度可使渗透增加一倍（p<0.05）。模型模拟表明，NAL 的药代动力学特征可与 FDA 批准的肌内和鼻内装置获得的特征相媲美。微针介导的透皮传递有可能实现阿片类药物过量治疗中纳洛酮的快速和持续传递。
