Tobin Kevin V, Fiegel Jennifer, Brogden Nicole K
Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa College of Pharmacy, Iowa City, IA 52242, USA.
Department of Chemical and Biochemical Engineering, University of Iowa College of Engineering, Iowa City, IA 52242, USA.
Polymers (Basel). 2021 Mar 18;13(6):933. doi: 10.3390/polym13060933.
Transdermal delivery of naltrexone (NTX) can be enhanced using microneedles, although micropores generated this way can reseal by 48 h in humans, which prevents further drug delivery from a formulation. Poloxamer 407 (P407) is a thermosensitive polymer that may extend microneedle-assisted NTX delivery time by creating an in situ gel depot in the skin. We characterized gelation temperature, drug release, and permeation of P407 gels containing 7% NTX-HCl. To investigate microneedle effects on NTX-HCl permeation, porcine skin was treated with microneedles (600 or 750 μm length), creating 50 or 100 micropores. The formulations were removed from the skin at 48 h to simulate the effect of micropores resealing in vivo, when drug delivery is blunted. Gelation temperature increased slightly with addition of NTX-HCl. In vitro NTX-HCl release from P407 formulations demonstrated first order release kinetics. Microneedle treatment enhanced NTX-HCl permeation both from aqueous solution controls and P407 gels. Steady-state flux was overall lower in the P407 conditions compared to the aqueous solution, though ratios of AUCs before and after gel removal demonstrate that P407 gels provide more sustained release even after gel removal. This may be beneficial for reducing the required application frequency of microneedles for ongoing treatment.
使用微针可增强纳曲酮（NTX）的透皮给药，不过以这种方式产生的微孔在人体中48小时内会重新封闭，这会阻止制剂进一步给药。泊洛沙姆407（P407）是一种热敏聚合物，它可能通过在皮肤中形成原位凝胶储库来延长微针辅助的NTX给药时间。我们对含有7%盐酸纳曲酮（NTX-HCl）的P407凝胶的凝胶化温度、药物释放和渗透进行了表征。为了研究微针对NTX-HCl渗透的影响，用微针（长度为600或750μm）处理猪皮，形成50或100个微孔。48小时后从皮肤上移除制剂，以模拟体内微孔重新封闭的效果，此时药物递送会减弱。随着NTX-HCl的加入，凝胶化温度略有升高。P407制剂的体外NTX-HCl释放呈现一级释放动力学。微针处理增强了NTX-HCl从水溶液对照和P407凝胶中的渗透。与水溶液相比，P407条件下的稳态通量总体较低，不过凝胶移除前后的AUC比值表明，即使在凝胶移除后，P407凝胶也能提供更持续的释放。这可能有利于减少持续治疗中微针所需的应用频率。
