Transdermal Drug Delivery System Using Light and Moisture Dual Responsive Hybrid Microneedles

Microneedles (MNs), which are transdermal drug delivery systems that can replace traditional drug delivery methods, have attracted attention in the pharmaceutical and cosmetic fields because they are patient-friendly and minimally invasive. However, the development of strategies for efficient delivery is still required owing to the limitations of drug release kinetic controllability. In the present study, we proposed a hybrid MN platform consisting of hyaluronic acid (HA) and gold nanorods (GNRs) that releases drugs in response to the dual stimulation of moisture and light. The MN patch was manufactured through physical polymer matrix entanglement using a biodegradable HA backbone and near-infrared (NIR)-responsive GNRs using a facile molding method, leading to the dissolution of the MN structure in response to microenvironmental moisture in the body. The integrated plasmonic GNRs improve the mechanical strength of the MN skeleton, and provide light-responsive properties under resonant light, allowing local heat generation by the photothermal conversion effect, which eventually accelerates the dissolution of the MN and rapidly releases the loaded drug in the MN. As a result, we achieved a significantly deeper penetration (2.70-fold deeper) and an enhanced capability for drug diffusion (1.69-fold farther), leading to a remarkable expansion in both surface diffusion area (5.40-fold wider) and intradermal diffusion area (3.04-fold larger) into skin tissue under NIR illumination conditions. These properties notably enhance the efficacy of inhibiting cancer cell proliferation by administering anticancer drugs through the application of MNs. Through in vivo experiments, we verified 40% inhibition of tumor growth compared to the control group. We anticipate that the proposed hybrid MN patch with dual-stimulus responsiveness will emerge as a promising platform for drug delivery and therapeutics, owing to its ability to facilitate the controlled and enhanced release of bioactive substances.