Microneedles Constructed by Swellable Hydrogels Loaded with Celastrol for Efficient Treatment of Skin Infections Induced by Drug-Resistant Bacterial Strains

The urgent need for new antimicrobial drugs arises from the limited efficacy of traditional antibiotics against emerging drug-resistant strains. Celastrol (CSL) demonstrates an exceptional antibacterial property that remains unaffected by bacterial resistance, but its poor water solubility limits its wide applications. This study uses the hydrophobic inner cavity of mono-(6-diethylenetriamine-6-deoxy)-β-cyclodextrin (mβ-CD) (a derivative of cyclodextrin) to encapsulate CSL, constructing an inclusion complex (CSL@mβ-CD) to enhance the water solubility of CSL. The obtained inclusion complex is further incorporated into a swellable hydrogel microneedle (MN) to obtain CSL@mβ-CD/MN. The fabricated CSL@mβ-CD/MN can enable the sustained release of CSL, achieving effective bacterial eradication at infected sites. In vivo experiments demonstrate that CSL@mβ-CD/MN has a remarkable efficacy in the treatment of methicillin-resistant <i>Staphylococcus aureus</i>-induced subcutaneous abscesses and wound infections. Specifically, CSL@mβ-CD/MN can effectively penetrate the stratum corneum of the skin to realize rapid elimination of the bacteria in wounds. Moreover, CSL@mβ-CD/MN can efficiently scavenge reactive oxygen species, promote M2 polarization of macrophages, and relieve local inflammation at the wound sites. These results reveal that CSL@mβ-CD/MN holds great promise in the clinical treatment of acute skin infections induced by drug-resistant bacteria.