TSA-SAB Co-Loaded Liposome Self-Dissolving Microneedle Synergistic Delivery System: A Breakthrough Dual-Drug Loading Strategy for Multi-Target Therapy of Hypertrophic Scars

The treatment of hypertrophic scars is constrained by inefficient transdermal delivery and challenges in co-delivery of multiple drugs. Although tanshinone IIA and salvianolic acid B exhibit multi-target antifibrotic potential, their divergent physicochemical properties limit combined application. This study proposes a novel transdermal system integrating co-loaded liposomes with dissolving microneedles (DMNs). TSA-SAB liposomes were prepared via thin-film dispersion with pH gradient method, optimized using Box-Behnken design to overcome traditional single-factor limitations. High-efficiency co-loading was achieved for lipophilic TSA (encapsulation efficiency: 86.10%) and hydrophilic SAB (98.43%). Integration with centrifugally cast microneedles yielded loadings of 216.01 μg/patch (TSA) and 371.65 μg/patch (SAB). Leveraging microneedle-mediated penetration and liposomal sustained release, the system showed 3-fold higher transdermal efficiency than free drugs, establishing a dermal reservoir. In vitro release followed Higuchi model (24 h: 68.33% TSA, 76.33% SAB) without burst release. Integrating nanocarriers with microneedles, this study provides a strategy to address multi-drug incompatibility and transdermal barriers, laying groundwork for HS therapy translation.