Thermosensitive Gels Used to Improve Microneedle-Assisted Transdermal Delivery of Naltrexone.
Thermosensitive Gels Used to Improve Microneedle-Assisted Transdermal Delivery of Naltrexone.
复制标题
DOI：
10.3390/polym13060933
复制
发表时间：
2021-03-18
期刊：
影响因子：
5
通讯作者：
Brogden NK
中科院分区：
文献类型：
--
作者：
Tobin KV;Fiegel J;Brogden NK
使用微针可以增强纳曲酮（NTX）的透皮给药，尽管这种方式产生的微孔在人体内可以在48小时后重新密封，这阻止了配方进一步给药。poloxam407 （P407）是一种热敏聚合物，可以通过在皮肤中形成原位凝胶库来延长微针辅助的NTX给药时间。我们对含有7% NTX-HCl的P407凝胶的凝胶温度、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，用长度为600 μm或750 μm的微针处理猪皮肤，形成50或100个微孔。48小时后将配方从皮肤中取出，以模拟体内微孔重新封闭的效果，当药物传递变钝时。加入NTX-HCl后，凝胶温度略有升高。P407制剂中NTX-HCl的体外释放表现为一级释放动力学。微针处理增强了水溶液对照和P407凝胶对NTX-HCl的渗透。与水溶液相比，P407条件下的稳态通量总体较低，尽管去除凝胶前后auc的比率表明，P407凝胶即使在去除凝胶后也能提供更持久的释放。这可能有利于减少持续治疗所需的微针应用频率。
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.
登录
查看更多内容
影响因子：
5.4
作者：
Khan, Samiullah;Minhas, Muhammad Usman;Thakur, Raghu Raj Singh
通讯作者：
Thakur, Raghu Raj Singh
影响因子：
3.4
作者：
Dumortier, G;El Kateb, N;Chaumeil, JC
通讯作者：
Chaumeil, JC
影响因子：
4.9
作者：
Milewski, Mikolaj;Paudel, Kalpana S.;Stinchcomb, Audra L.
通讯作者：
Stinchcomb, Audra L.
影响因子：
5.8
作者：
Ricci, EJ;Lunardi, LO;Marchetti, JM
通讯作者：
Marchetti, JM
影响因子：
4.8
作者：
Bodratti AM;Alexandridis P
通讯作者：
Alexandridis P