Synthesis, characterization, and efficacy of antimicrobial chlorhexidine hexametaphosphate nanoparticles for applications in biomedical materials and consumer products

Abstract

Michele E Barbour,1 Sarah E Maddocks,2 Natalie J Wood,1,3 Andrew M Collins3 1Oral Nanoscience, School of Oral and Dental Sciences, University of Bristol, Bristol, UK; 2Cardiff School of Health Sciences, Cardiff Metropolitan University, Cardiff, UK; 3Bristol Centre for Functional Nanomaterials, University of Bristol, Bristol, UK Abstract: Chlorhexidine (CHX) is an antimicrobial agent that is efficacious against gram-negative and -positive bacteria and yeasts. Its mechanism of action is based on cell membrane disruption and, as such, it does not promote the development of bacterial resistance, which is associated with the widespread use of antibiotics. In this manuscript, we report the development of novel antimicrobial nanoparticles (NPs) based on a hexametaphosphate salt of CHX. These are synthesized by instantaneous reaction between equimolar aqueous solutions of CHX digluconate and sodium hexametaphosphate, under room temperature and pressure. The reaction results in a stable colloid composed of highly negatively charged NPs (−50 mV), of size 20-160 nm. The NPs adhere rapidly to specimens of glass, titanium, and an elastomeric wound dressing, in a dose-dependent manner. The functionalized materials exhibit a gradual leaching of soluble CHX over a period of at least 50 days. The NP colloid is efficacious against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in both planktonic and biofilm conditions. These NPs may find application in a range of biomedical and consumer materials. Keywords: MRSA, biomaterials, chlorhexidine, drug delivery, slow release