Abstract

Wounds associated with diabetes are difficult to heal and often stay unhealed, leading to higher morbidity and mortality in the diabetic population. A major barrier to the successful healing of chronic diabetic wounds is the presence of biofilm-mediated infections. In recent years, photodynamic therapy (PDT) has emerged as a promising treatment modality for the management of chronic wounds. The objective of the present study was to evaluate the effectiveness of toluidine blue- (TB-) loaded nanoparticle-mediated PDT in eradicating antibiotic-resistant polymicrobial biofilms ofPseudomonas aeruginosaand methicillin-resistantStaphylococcus aureusin anin vitromodel. Dioctyl sodium sulfosuccinate (aerosol OT, AOT)-alginate nanoparticles with high TB loading (10.8±2.2%) were formulated using a double emulsification cross-linking method. TB nanoparticles induced effective killing of planktonicP.aeruginosa(3.5 log10CFU) andS.aureus(>5 log10CFU) and their combined biofilms (2.8 log10CFU forP.aeruginosaversus 3.4 log10CFU forS.aureus). WhileP.aeruginosabiofilm was more resistant when compared to that ofS.aureus, our results demonstrated effective eradication of complex biofilms of dual bacterial strainsin vitro.

Highlights

  • Chronic wounds are a major health problem throughout the world, with limited effective methods of treatment

  • Biofilm-embedded bacteria are difficult to treat, as they are often resistant to antibiotics and the host immune system

  • photodynamic therapy (PDT) has evolved as a potential alternative therapeutic strategy since this modality is not susceptible to resistance mechanisms found in bacteria [39]

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Summary

Introduction

Chronic wounds are a major health problem throughout the world, with limited effective methods of treatment. Wounds associated with diabetes are difficult to heal and often remain unhealed leading to increased morbidity and mortality in diabetic patients [1, 2]. A key barrier to the successful healing of chronic diabetic wounds is the presence of biofilm-mediated infections [3,4,5]. The polymicrobial nature of diabetic wounds appears to promote the production of several virulence factors that contribute to the chronicity of the infection [12, 13]. Presence of antibioticresistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) is more common in diabetic wounds [14]

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