Degradable microneedle patches loaded with antibacterial gelatin nanoparticles to treat staphylococcal infection-induced chronic wounds

Abstract

Infection-induced chronic wounds cause prolonged pains, a high risk of amputation, and even increased mortality in immunocompromised patients. Here we report an antibacterial microneedle (MN) patch, which features high degradability in biological fluids and gelatinase-responsive release of an antibacterial photothermal peptide AMP-Cypate. We first synthesize gelatin nanoparticles (GNPs) and then conjugate the AMP-Cypate to afford composite AMP-Cypate@GNPs. The proteinaceous nanoparticles can responsively release AMP-Cypate in the presence of gelatinase, an enzyme secreted specifically by Staphylococcus aureus (S. aureus). AMP-Cypate@GNPs were then deposited in the tips of MNs fabricated by PVP and recombinant human type III collagen (Col III) to devise the antibacterial MN/AMP-Cypate@GNP patches. When applied to the infection site, MNs break through the epidermis and the stratum corneum, dissolve in the infected dermis, reach the bacterial colony or biofilm, release AMP-Cypate@GNPs, and exert a gelatinase-responsive photothermal therapy under near-infrared (NIR) irradiation to kill the pathogen S. aureus. In a rat model of staphylococcal infection-induced chronic wounds mimicking the condition of diabetic foot ulcer, the antibacterial MN/AMP-Cypate@GNP patches eradiated the bacterial infection and resulted in complete healing of the wounds, proving its potential application in the treatment of chronic wound infections and diabetic foot ulcers.

Keywords: Antibacterial photothermal peptide; Degradable microneedle; Diabetic foot ulcer; Gelatinase-responsive release; Recombinant human type III collagen.