Implantable core-shell microneedles enable biphasic release of insulin for immediate and sustained glycemic regulation.

Insulin delivery is fundamental to diabetes management; however, conventional monophasic release systems often fail to achieve both rapid glycemic correction and sustained basal regulation. In this study, we developed an implantable core-shell biphasic-release microneedle (MN) system engineered to enable independent dual-stage insulin kinetics. The platform comprises a fast-dissolving gelatin shell and a sustained-release, self-healing porous poly(lactic-co-glycolic acid) (PLGA) core, supported by a rigid resin micropillar array. The porous PLGA core was fabricated via cryogenic demolding and phase separation to allow diffusive insulin loading, followed by mild thermally induced self-healing to seal and encapsulate the drug. The outer gelatin shell was prepared through its reversible sol-gel transition at 4 °C, providing a gentle, low-temperature encapsulation environment that preserves insulin bioactivity. The supporting resin micropillars enhance skin penetration depth and facilitate facile detachment, allowing the drug-loaded tips to remain embedded in the dermis as intradermal depots. In vitro and in vivo release studies demonstrated a well-defined biphasic profile, characterized by an initial rapid release from the gelatin shell for prompt glycemic reduction, followed by sustained release from the PLGA core to maintain prolonged glucose homeostasis. In diabetic rat models, the system reduced blood glucose levels within 3 h and maintained therapeutic efficacy for up to 7 days without inducing the hypoglycemia commonly associated with bolus injections. By integrating a core-shell architecture with a mild encapsulation strategy, this platform provides a promising approach for efficient and patient-friendly management of chronic metabolic disorders.