Triclosan Loaded pH-sensitive Vehicles Spray Facilitate Infected Wound Healing by Eliminating Methicillin Resistant Staphylococcus Aureus in Biofilm

Abstract

Abstract The use of conventional antibiotics has rapidly declined due to the development of antibiotic resistance. Therefore, there is an urgent need for the development of novel vehicles to facilitate effective antibiotics delivery, especially for bacteria that form biofilm. Herein, we designed a library of pH-sensitive polymer vehicles with pKa values ranging from 6.2-5.0. We found that pKa values located into 5.3-5.7 displayed certain antibacterial effect and effective biofilm elimination. The antibacterial effect the copolymer vehicles is highly pKa dependent. Regardless of physical environment or pH 5.6 conditions, biofilm elimination improved silightly. Among the five vehicles, the copolymer (PEPB36/35) with pKa about 5.7 not only exhibited the best biosafety, but also significantly improved the biocompatibility of antibiotics triclosan (TCS). Moreover, PEPB36/35 nanoparticles (NPs) destroyed cell membranes and promoted cargos into cells under an acidic environment. The formed of PEPB36/35@TCS NPs spray was able to kill Methicillin Resistant Staphylococcus Aureus (MRSA) in biofilm and accelerate infected wound healing, which reduced inflammation and promoted angiogenesis. Collectively, these findings affirm that the designed pH-sensitive vehicles improve antibacterial efficacy of TCS in killing bacteria in biofilm.