Biocompatible Glue-Enabled Drug Localization and Mechanical Reinforcement of Lyophilized Microneedle Systems

Clinical translation of dissolving microneedles (DMNs) is hindered by critical challenges such as drug diffusion into the backing layer during fabrication and slow dissolution rates, which compromise dose accuracy, delivery efficiency, and user compliance. Although lyophilization has emerged as a strategy to accelerate microneedle dissolution by inducing a porous, amorphous microstructure, the resulting mechanical fragility limits effective skin insertion. To overcome these issues, we developed a Lyophilized Microneedle System using Biocompatible Glue (LMS-BG), wherein a lyophilized, drug-loaded microneedle tip is coupled with a prefabricated backing via a biodegradable, ethanol-based glue (BC glue). This system enables tip-localized drug confinement, rapid dissolution, and mechanical reinforcement through partial interpenetration of BC glue into the porous tip. Using lidocaine hydrochloride (LiH) as a model drug, LMS-BG exhibited an 11-fold faster dissolution rate than conventional DMNs, with over 96% of the drug retained in the tip and a transdermal delivery efficiency exceeding 90% within 2 min. In vivo studies in rats confirmed superior local anesthetic efficacy and biocompatibility of LMS-BG compared to commercial lidocaine gel. Furthermore, the LMS-BG fabrication method was successfully extended to various microneedle platforms using soluble polymers, hydrogels, and PLGA nanoparticles, demonstrating its scalability and versatility. Overall, the LMS-BG platform addresses key translational barriers of conventional DMNs and presents a modular strategy for rapid, efficient, and clinically viable transdermal drug delivery.