Acupoint-administered sinapine thiocyanate-loaded dissolvable microneedles for bronchial asthma: dose-response...

Bronchial asthma (BA) is a chronic inflammatory airway disease for which conventional drug delivery routes show limited therapeutic efficacy. Herbal acupoint application offers targeted therapeutic benefits by combining pharmacological effects with specific acupoint stimulation; however, conventional patches are limited by poor sustained release and low patient compliance. Sinapine thiocyanate, a natural alkaloid with anti-inflammatory properties, has potential for asthma treatment, yet its poor bioavailability hinders its therapeutic application. To address these gaps, we developed sinapine thiocyanate‑loaded dissolvable microneedles (ST‑DMN) using polyvinylpyrrolidone K30 (PVP‑K30) and chondroitin sulfate (CS) as matrix materials, and polyvinyl alcohol (PVA) as the backing layer, designed for acupoint administration to achieve sustained drug release and improve therapeutic outcomes. ST-DMN patches with drug loadings ranging from 0.25 to 2.0 mg/patch were prepared, and a dose-response relationship was established in a rat model of BA to identify the optimal drug loading. The results demonstrated that ST-DMN at 1.5 and 2.0 mg/patch significantly improved the behavioral status of asthmatic rats, increased immune organ coefficients, and reduced the expression of IgE, TNF-α, and IL-1β. Based on a comprehensive assessment of efficacy and safety, 1.5 mg/patch was selected as the optimal dose. Network pharmacology analysis predicted that the PI3K/AKT signaling pathway was highly relevant to the anti-asthmatic effects of sinapine thiocyanate. Subsequent validation in animal models confirmed that the optimal dose of ST-DMN effectively ameliorated lung tissue pathology and reduced inflammatory cell infiltration. Furthermore, ST-DMN treatment significantly decreased the expression levels of key inflammatory factors and inhibited PI3K and AKT phosphorylation. The current findings suggest that ST-DMN at 1.5 mg/patch exerts therapeutic effects against BA through acupoint administration, likely by modulating the PI3K/AKT signaling pathway and suppressing inflammatory responses.