Recyclable Polymerizable Deep Eutectic Solvent-Based Three-Dimensional-Printed Dissolving Microneedles with pH-Responsive Delivery of ZIF-8-Loaded Minoxidil for Hair Loss Therapy

Hair loss remains a prevalent dermatological concern with limited options for targeted, sustained transdermal therapy. Conventional topical formulations of minoxidil (MXD) suffer from poor skin penetration, rapid clearance, and low patient compliance. To address these limitations, we developed a three-dimensional-printed, dissolving microneedle (MN) system featuring a novel layered design: a recyclable polymerizable deep eutectic solvent (PDES) base and detachable, pH-responsive tips loaded with MXD-encapsulated ZIF-8 nanoparticles. This design allows for rapid insertion and dissolution of the drug-loaded needle tips, enabling the sustainable recovery and reuse of the PDES base through a simple ethanol-based regeneration protocol. The MNs exhibited excellent print fidelity, mechanical integrity (>50 mN fracture force), and skin penetration capability, along with minimal cytotoxicity and hemolysis. In vitro and in vivo evaluations confirmed pH-triggered drug release and potent hair regrowth performance in a cyclophosphamide-induced alopecia mouse model. Histological analysis revealed enhanced hair follicle density and demonstrated minimal systemic toxicity, highlighting its safety profile. Overall, this layered dissolving-recyclable MN platform for pH-triggered delivery of ZIF-8-encapsulated MXD represents a promising, sustainable strategy for transdermal delivery to treat hair loss.