Thermal-enhanced self-heating microneedle patch for sustained progesterone delivery and improved pregnancy maintenance

Progesterone (PG) deficiency is a leading cause of impaired pregnancy maintenance, while current therapies such as frequent intramuscular injections suffer from poor compliance, inconvenience, and clinical risks. To address these issues, we report a self-heating microneedle (MN) patch designed for comfortable, sustained, and efficient thermally enhanced transdermal delivery of PG. The integrated system incorporates PG-loaded MNs, a 3D-printed backing layer with trigger mechanism, and a quicklime/activated charcoal (CaO + C) exothermic mixture that enables controllable and efficient self-heating effects (>60 °C). In vitro and in vivo drug release studies demonstrate that efficient and sustained thermal conduction facilitates polymer dissolution, accelerates drug release and diffusion (by > 70%), enhances skin permeability, and improves local blood flow, supporting systemic circulation. In a pregnant rat model, a single patch application maintained therapeutic PG levels for over 10 h and was associated with improved neonatal survival and reduced preterm birth. This self-administered patch, with proven biosafety and no need for external devices, presents a convenient, compliant, low-cost, and highly efficient strategy for PG supplementation, and warrants further investigation in pregnancy maintenance.