Microneedles\nConstructed by Swellable Hydrogels Loaded\nwith Celastrol for Efficient Treatment of Skin Infections Induced\nby Drug-Resistant Bacterial Strains

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