Multifunctional eutectogel for co-delivery of baicalein and metformin to promote diabetic wound healing

Natural products have made significant contributions to human therapeutics. However, approximately 90% of these compounds face severe limitations in clinical application due to challenges such as poor water solubility, low bioavailability and instability. Although combining natural products with synthetic drugs has demonstrated synergistic advantages in treating various diseases, their therapeutic potential for diabetic wound healing remains largely unexplored. A key obstacle lies in the significant differences in solubility between these two drugs, which severely hinders the development of combination formulations. This study developed a dual-drug-loaded gel system (Bai-Met/DES-Gel) based on a deep eutectic solvent (DES) and carbomer 940. The solubility of baicalein was enhanced to 26.72 mg ml^-1, enabling its stable co-dissolution with the synthetic metformin. The drug delivery system exhibited sustained-release properties, good biocompatibility, significant antibacterial activity againstE. coliandS. aureus, and excellent DPPH radical scavenging capacity. In the diabetic rat wound model, Bai-Met/DES-Gel effectively accelerated wound healing by inhibiting inflammatory responses, promoting granulation tissue formation, facilitating collagen alignment, stimulating angiogenesis, and enhancing cell proliferation. This study advanced the potential application of DES on co-delivery of natural and synthetic drugs, while providing a novel solution for the treatment of diabetic wounds.