Mehran Alavi - Department of Biological Science, Faculty of Science, Kurdistan University, Sanandaj, Kurdistan, Iran; Nanobiotechnology Department, Faculty of Innovative Science and Technology, Razi University, Kermanshah, Iran
Michael Hamblin - Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, ۲۰۲۸, South Africa; Wellman Centre for Photomedicine, Massachusetts General Hospital, Boston, MA ۰۲۱۱۴, USA; Department of Dermatology, Harvard
Fleming Martinez - Department of Pharmacy, Faculty of Sciences, Universidad Nacional de Colombia, South America, Colombia
Ermia Aghaie - High Performance Powertrain Materials Laboratory, School of Engineering, University of British Columbia – Okanagan, Kelowna, V۱V ۱V۷, Canada
Haroon Khan - Department of Pharmacy, Abdul Wali Khan University Mardan, Pakistan
Irwin Menezes - Pharmacology and Molecular Chemistry Laboratory, Department of Chemical Biology, Regional University of Cariri, CEP ۶۳۱۰۵-۰۰۰, Crato, Ceara, Brazil

Diabetes mellitus is a metabolic disease, which in a severe form needs daily subcutaneous injections of insulin to prevent symptoms, especially diabetic foot ulcers (DFU). However, the emergence of multidrug-resistant (MDR) bacteria in diabetic wounds can lead to complications. The infection of DFUs by MDR bacteria can lead to biofilm formation, and can increase the risk of lower-limb amputation up to ۸۰%. Insulin hormone can activate angiogenesis, migration and proliferation of keratinocytes, and lead to the rapid maturation and closure of wounds. Insulin can promote protein and lipid synthesis, inactivate NFkβp۵۰/p۶۵, as well as altering cytokine dynamics. However, the uncontrolled and burst release of insulin reduces the therapeutic effects after topical delivery to wound tissues. Therefore a novel strategy for insulin delivery involves various polymeric and liposomal formulations on the micro or nanoscale, for sustained and controlled release of this hormone. In addition, improved sensitivity and selectivity are two major advantages (compared to free insulin) reported for nanoformulations of insulin. This review summarizes the current knowledge about the efficacy and limitations of these formulations to treat infected chronic wounds, especially in diabetics.

Diabetes Mellitus, Diabetic foot ulcers, insulin, Polymeric nanoparticles, liposomal formulation, Angiogenesis, keratinocytes, Cytokine dynamic, wound healing