Hyaluronic acid microneedle patch for transdermal delivery of frankincense and myrrh bioactives to alleviate inflammation and enhance diabetic ulcer healing

Abstract

Chronic inflammation impedes the healing of diabetic ulcers (DUs), while P-glycoprotein (P-gp)-mediated drug efflux reduces the efficacy of conventional drug formulations. In this study, a novel liposome-mediated hyaluronic acid (HA) microneedle patch (E-Lipo@A-HMN) was developed for enhanced DUs healing via the transdermal delivery of Acetyl-11-keto-β-boswellic acid (AKBA) and β-elemene (ELE). The findings demonstrate that liposomal encapsulation enhances the solubility and bioavailability of ELE, and HA microneedles improve skin penetration and enable controlled drug release by providing a biodegradable, biocompatible scaffold that improves skin penetration and enables controlled drug release. Furthermore, our treatment protocol could effectively attenuate inflammation and promote fibroblast proliferation, collagen deposition and angiogenesis by inhibiting P-gp expression, enhancing intracellular drug accumulation and downregulating the PI3K/AKT/NF-κB signaling pathway. Compared to conventional therapies, E-Lipo@A-HMN exhibits better therapeutic performance, demonstrating enhanced anti-inflammatory activity and accelerated wound repair. Moreover, the treatment protocol displays an excellent biosafety profile. It offers a novel, safe, and effective therapeutic strategy for treating DUs with significant potential for clinical application.