in-vitro and in-vivo evaluation of doxycycline hyclate and piroxicam loaded chitosan nanoparticles into transdermal patch for healing diabetic foot ulcer

Diabetic foot ulcer (dfu) pose a significant clinical challenge in hyperglycaemic patients, characterized by delayed healing, susceptibility to infection, and persistent inflammation. chitosan, a natural polysaccharide with antimicrobial, hemostatic, wound healing, and moisture retention properties, is targeted for dfu therapy through transdermal application utilizing nanotechnology. this study aims to formulate and evaluate transdermal patches based on doxycycline hyclate (dch) and piroxicam (px) loaded with chitosan nanoparticles (cnps) for enhanced wound healing in dfu.the ion gelation method was employed for nanoparticle preparation. the nanoparticles were characterized using zetasizer, dls, fe-sem, ft-ir, xrd, and dsc were used to assess the physical mixture, crystalline nature, and thermal behavior of the drugs and excipients. transdermal patches were grafted using the solvent casting technique and evaluated for physicochemical parameters, in vitro 24-hour drug release studies, and in vivo diabetic rat foot ulcer healing. the synthesized nanoparticles were spherical, with a particle size ranging from 237 to 330 nm and a zeta potential of -23 mv. in vivo studies on diabetic rat foot ulcer healing using a streptozotocin-induced excision wound model demonstrated significant wound healing and closure after 17 days of therapy. the f5 formulation remained stable for 6 months under accelerated conditions, maintaining drug content above 85% according to ich guidelines. the optimized f5 transdermal patch exhibited desirable physicochemical properties, drug content uniformity, and sustained drug release, indicating its potential for dfu therapy.