Iron Oxide Nanoparticle-Powered Micro-Optical Coherence Tomography for in Situ Imaging the Penetration and Swelling of Polymeric Microneedles in the Skin

In recent years, polymeric microneedles (MNs) have attracted keen interests among researchers because of their applicability in transdermal drug delivery and interstitial skin fluid (ISF) extraction. When designing and characterizing such devices, it is critical to monitor their real-time in vitro and in vivo performances to optimize the desired effects, yet most of the existing methods are incapable of such functions. To address this unmet need, we develop a real-time noninvasive imaging methodology by integrating iron oxide (Fe3O4) nanoparticles into polymeric MNs to enhance image contrast for micro-optical coherence tomography (mu OCT) imaging. Using the Fe3O4-integrated polystyrene-block-poly(acrylic acid) (PS-b-PAA) MNs as an example, we evaluate the influences of Fe3O4 concentrations on contrast enhancement in mu OCT imaging and visualize the real-time swelling process of polymeric MNs in biological samples for the first time. Our results show that a concentration of similar to 4-5 wt % Fe3O4 nanoparticles not only helps achieve the best contrast-to-noise ratio in mu OCT imaging, which is 10 times higher than that without Fe3O4 nanoparticles in air and hydrogel, but also enables the real-time changes in the profile of MNs to be observed clearly in their swelling process in skin tissues. On the basis of such findings, we utilize the optimized concentration of Fe3O4 nanoparticles to further quantitatively study the swelling kinetics of PS-b-PAA MNs in agarose hydrogel and fresh skin tissues, which lasts similar to 20 and similar to 30-35 s, respectively. The suitability of such a methodology for enhancing mu OCT imaging would greatly facilitate the development and clinical translation of MN-based medical technologies.