A bilayer dissolving microneedle for Co-delivery of Bletilla striata polysaccharide and resveratrol to promote synergistic wound healing.

Effective wound management remains a significant clinical challenge, often hindered by inadequate drug delivery and compromised healing environments. To solve this, a double-layer dissolving microneedle (MN) patch was developed for synergistic, sequential delivery of Bletilla striata polysaccharide (BSP) and resveratrol (Res). Res's poor aqueous solubility was addressed by encapsulating it in 2-hydroxypropyl-β-cyclodextrin (Hp-β-CD) to form a stable complex. MNs were made via a two-step casting method: the Res-loaded tip layer released drugs quickly, while the BSP-based backing layer provided sustained bioactivity and structural support. The BSP/Hp-β-CD@Res MNs had good mechanical strength and skin penetration, creating microchannels up to 381 μm deep. They were biocompatible, with no cytotoxicity and hemolysis below the 5 % safety threshold. In vitro, they inhibited NO production in LPS-stimulated macrophages, promoted fibroblast migration and achieved 46.08 ± 3.18 % scratch closure in 48 h. In a murine full-thickness skin defect model, they accelerated wound closure to 95.7 ± 1.91 % by day 10, outperforming controls. With its demonstrated efficacy and controlled delivery mechanism, this multifunctional MN patch holds significant translational potential to shift current treatment paradigms and improve outcomes for patients with challenging wounds.