Impaired closure of diabetic ulcers is a serious complication decreasing quality of patient’s life. The cause is overexpression of metalloproteinases (MMPs) during reepithelialization. Inhibitors of metalloproteinases are low effective so far and their use leads to serious side effects. The proposed translational research is focused on preclinical development of a system for treatment of impaired closure of ulcers. It’s based on effective and safe gene therapy – RNA interference of selected MMP. The carrier, nanodiamonds – the carbon nanomaterial with the lowest known toxicity – bears polyethyleneimine which stabilizes the therapeutic siRNA and facilitates its transfection. The whole system is incorporated in nanofibers which serve for localized release of the therapeutic complex and maintenance of constant siRNA level for the time necessary for the closure of ulcer. The completion of project will enable to follow with preclinical trials in vivo using primates and possible translation of the therapeutic procedure to clinical outputs.
Aim: Development of a new gene therapy nanosystem for improvement of diabetic ulcers treatment. Controlled release of siRNA will be achieved by nanodiamond particles bearing polyethyleneimine. For localized action the system will be incorporated in biocompatible nanofibers.
Nanofibres and encapsulated nanodiamonds (red signal, arrows) vizualisation by a classic confocal microscopy:
Visualization of nanofibres via electron microscopy: