A co-amorphous salt of ursodeoxycholic acid and matrine incorporated into dissolving microneedles for combined antibacterial and anti-inflammatory treatment of acne vulgaris.

Acne vulgaris is characterized by microbial dysbiosis and excessive inflammatory activation, whereas current topical therapies are often limited by poor skin penetration and increasing antibiotic resistance. Ursodeoxycholic acid (UDCA) has anti-inflammatory potential but suffers from low aqueous solubility and limited cutaneous permeability. In this study, a co-amorphous salt of UDCA and matrine (MAT) was developed to improve the pharmaceutical performance of UDCA and to combine the complementary activities of the two components. UDCA-MAT was further incorporated into hyaluronic acid-based dissolving microneedles (UM-MNs) to enhance local transdermal delivery. FTIR, DSC, and PXRD confirmed amorphization and ionic interaction between UDCA and MAT. Compared with UDCA alone, UM increased the apparent aqueous solubility of UDCA by approximately 2302-fold and significantly improved ex vivo skin permeation. In vitro, UM showed stronger growth-inhibitory effects against Cutibacterium acnes within the tested concentration range and more effectively reduced the expression of IL1B, IL6, CXCL8, and TNF in stimulated HaCaT cells, accompanied by reduced NF-κB p65 nuclear translocation. In a murine acne model, UM was associated with reduced lesion size, bacterial burden, and inflammatory cytokine levels relative to the single-component groups under the present experimental conditions. UM-MNs showed adequate mechanical strength, achieved effective skin insertion, and enabled continued drug release over 24 h. Compared with topical gel, UM-MNs were associated with greater improvement in lesion morphology and local inflammatory status, together with reduced activation of the C. acnes-related TLR2/4-NF-κB pathway in vivo. These findings support a formulation-based, antibiotic-sparing strategy for acne treatment through co-amorphous salt engineering combined with microneedle-assisted delivery.