材料科学
药物输送
体内
透皮
纳米技术
生物医学工程
药理学
医学
生物
生物技术
作者
Miguel Angel Lopez‐Ramirez,Fernando Soto,Chao Wang,Ricardo Rueda,Sourabh Shukla,Cristian Silva‐López,Daniel Kupor,David A. McBride,Jonathan K. Pokorski,Amir Nourhani,Nicole F. Steinmetz,Nisarg J. Shah,Joseph Wang
标识
DOI:10.1002/adma.201905740
摘要
The use of microneedles has facilitated the painless localized delivery of drugs across the skin. However, their efficacy has been limited by slow diffusion of molecules and often requires external triggers. Herein, an autonomous and degradable, active microneedle delivery platform is introduced, employing magnesium microparticles loaded within the microneedle patch, as the built-in engine for deeper and faster intradermal payload delivery. The magnesium particles react with the interstitial fluid, leading to an explosive-like rapid production of H2 bubbles, providing the necessary force to breach dermal barriers and enhance payload delivery. The release kinetics of active microneedles is evaluated in vitro by measuring the amount of IgG antibody (as a model drug) that passed through phantom tissue and a pigskin barrier. In vivo experiments using a B16F10 mouse melanoma model demonstrate that the active delivery of anti-CTLA-4 (a checkpoint inhibitor drug) results in greatly enhanced immune response and significantly longer survival. Moreover, spatially resolved zones of active and passive microneedles allow a combinatorial rapid burst response along with slow, sustained release, respectively. Such versatile and effective autonomous dynamic microneedle delivery technology offers considerable promise for a wide range of therapeutic applications, toward a greatly enhanced outcome, convenience, and cost.
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