Composite microneedle-mediated co-delivery of magnesium hydride-magnolol for androgenetic alopecia

Androgenetic alopecia (AGA) impairs quality of life, yet current pharmacotherapies are hampered by limited efficacy and adverse effects. Microneedle-assisted transdermal co-delivery of bioactive natural products and gaseous agents offers a promising alternative. Herein, we report composite polymer microneedles (MNs) for controlled co-delivery of magnesium hydride (MgH₂, which generates cytoprotective H₂ and Mg²⁺ in vivo) and magnolol (Mag, a polyphenol with anti-inflammatory and antioxidant activities). Drug-loaded particles were fabricated via mechanical ball milling and ethanol solvent methods, characterized by XRD, FTIR and SEM, and then incorporated into dissolving PVA:PVP MNs by micromolding with two-step centrifugation. Ball milling yielded superior phase purity and a denser microstructure compared with ethanol, evidenced by distinct XRD peaks and intact FTIR signatures for both Mag and MgH₂. Optimized MNs exhibited markedly enhanced mechanical strength after drug loading (14.524 N vs. 10.729 N). In vitro release best followed first-order kinetics (R ² = 0.99879), reaching 96% at 40 °C or under UV irradiation versus 80.7% at ambient conditions. This MgH₂-Mag MN system combines robust mechanical resilience with thermoresponsive and photoresponsive release, providing a tunable transdermal platform for AGA intervention.