diazeniumdiolate and Wounds-and-Injuries

Wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) biofilm represent a high risk in patients with diabetes. Nitric oxide (NO) has shown promise in dispersing biofilm and wound healing. For an effective treatment of MRSA biofilm-infected wounds, however, NO needs to be supplied to the biofilm matrix in a sustainable manner due to a short half-life and limited diffusion distance of NO. In this study, polyethylenimine/diazeniumdiolate (PEI/NONOate)-doped PLGA nanoparticles (PLGA-PEI/NO NPs) with an ability to bind to the biofilm matrix are developed to facilitate the NO delivery to MRSA biofilm-infected wound. In simulated wound fluid, PLGA-PEI/NO NPs show an extended NO release over 4 days. PLGA-PEI/NO NPs firmly bind to the MRSA biofilm matrix, resulting in a greatly enhanced anti-biofilm activity. Moreover, PLGA-PEI/NO NPs accelerate healing of MRSA biofilm-infected wounds in diabetic mice along with complete biofilm dispersal and reduced bacterial burden. These results suggest that the biofilm-binding NO-releasing NPs represent a promising NO delivery system for the treatments of biofilm-infected chronic wounds.

Topics: Animals; Anti-Bacterial Agents; Azo Compounds; Biofilms; Diabetes Complications; Diabetes Mellitus, Experimental; Drug Liberation; Male; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred BALB C; Mice, Inbred ICR; Nanoparticles; Nitric Oxide; Polyethyleneimine; Polylactic Acid-Polyglycolic Acid Copolymer; Staphylococcal Skin Infections; Wound Healing; Wounds and Injuries