Bee Stinger-Like Wearable Electrospun Web Microneedles for Sustained CNS Drug Delivery

Microneedles (MNs) have emerged as a promising solution for pain-free and patient-friendly drug delivery. MNs provide therapeutic benefits with minimal invasiveness, thus reducing patient distress. However, although MNs have been proposed for the sustained delivery of drugs into the central nervous system (CNS), conventional rigid MNs lead to discomfort and fatigue during extended wear. In this study, wearable electrospun web MNs (EW-MNs) inspired by the mechanics of bee stingers are developed. Through the grounding of metal MNs and controlled formation of electrospun fibers, EW-MNs suitable for skin insertion and anchoring are fabricated. The penetration depth and drug diffusion performance are then evaluated. Sustained-release drug delivery along the fiber surface is validated using fluorescent dyes simulating a real therapeutic drug. Finally, the therapeutic mechanism and efficacy of EW-MNs loaded with CNS-targeted drugs, such as rivastigmine, are validated in guinea pig models, confirming their potential for continuous and effective CNS disease management. In vitro and in vivo evaluations showed a 2.5-fold increase in AUC and a fivefold expansion in drug diffusion area, demonstrating the efficacy of EW-MNs in sustained CNS drug delivery.