Universitas Indonesia Conferences, Asian Federation for Pharmaceutical Sciences (AFPS) 2019

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Biofilm Targeted-Nitric Oxide Releasing Polymeric Nanoparticles: Adhesion and Anti-biofilm Efficacy against MRSA Biofilm in diabetic wounds
Nurhasni Hasan, Jin-Wook Yoo

Last modified: 2019-06-15


Background: Biofilm-associated wound infections are a life-threatening infection that affects millions of people each year and among the major cause of infectious disease-related mortality and morbidity worldwide. 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. Objective: 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. Materials and Methods: PLGA was used to incorporate PEI/NONOates by an oil-in-water emulsion evaporation method to form PLGA-PEI/NO NPs. Adhesion of PLGA-PEI/NO NPs on bacterial biofilm and the progress of in vivo biofilm dispersal were performed in MRSA biofilm-infected wound and characterized by 3D confocal microscopy. Photographs of the wounds were taken to observe the gross visual wound healing. Furthermore, histological analysis was performed with H&E and Masson trichrome stain. Results: 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. Histopathology analysis showed an increase in fibroblast-like cells and collagen deposition associated with healed skin structures close to the healthy epidermis. Conclusion: These results suggest that the biofilm-binding NO-releasing NPs represent a promising NO delivery system for the treatments of biofilm-infected chronic wounds.