A matrix metalloproteinase-sensitive hydrogel combined with photothermal therapy for transdermal delivery of deferoxamine to accelerate diabetic pressure ulcer healing

Abstract

Diabetic pressure ulcers (DPU) are non-healing due to vascular dysfunction and bacterial infection. Early intervention can delay ulcer progression, such as preventing the formation of full-thickness skin defects. Local administration of deferoxamine (DFO) at wound sites has been shown to promote neovascularization and enhance wound healing. However, since DPU skin wounds are not full-thickness defects and DFO is hydrophilic, enhancing its transdermal delivery is crucial for effective treatment. Photothermal ablation of stratum corneum, generated by copper sulfide nanoparticles (CuS NPs) under near-infrared (NIR) light irradiation, is a promising method to improve transdermal drug delivery. Meanwhile, CuS NPs-induced photothermal therapy offers excellent antibacterial performance. In this study, DFO and CuS NPs were incorporated into a matrix metalloproteinase (MMPs)-sensitive hydrogel. This hydrogel promotes cell adhesion and is degraded by cell-secreted MMPs, a process crucial for the controlled release of encapsulated DFO and CuS NPs. Under NIR irradiation, the stratum corneum is disrupted, facilitating transdermal DFO delivery and simultaneously eliminating infected bacteria. As a result, the essential requirements for DPU treatment, “facilitating transdermal DFO delivery, promoting angiogenesis, and inhibiting bacterial infection”, were achieved simultaneously.