Journal
ADVANCED MATERIALS
Volume 32, Issue 1, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201905740
Keywords
3D printing; active drug delivery; magnesium microparticles; micromotors; microneedles; transdermal delivery
Categories
Funding
- Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense [HDTRA1-18-1-0014, HDTRA1-14-1-0064]
- NIH [R01CA224605, T32 AR064194]
- American Cancer Society [IRG-15-172-45]
- UC MEXUS-CONACYT Doctoral Fellowships
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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 H-2 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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