Thermo-responsive microneedles patch for transdermal drug delivery via squeezing in diabetic foot ulcers

Microneedle (MN) patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide. While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches, it can create toxic chemical residues or require the help of additional devices. Herein, a thermo-responsive microneedles patch (TMN) with high biocompatibility without additional equipment is proposed. The TMN consisted of a bilayer microneedles composed of sodium alginate (SA)-g-poly(N-isopropylacrylamide) layer (SA-g-PNIPAM) loaded with sucrose octasulfate sodium salt (SOS) and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride (TH) and SOS. PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes, and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation. The results showed that the drug release of TMN was significantly faster, with the drug release rate of more than 80% in the 10th h, and the antibacterial rate of TMN could reach 800%. In addition, TMN had good biocompatibility and good healing effects in vivo, which may be helpful for the design of multifunctional dressings in the future.