Construction of tea tree oil/salicylic acid/palygorskite hybrids for advanced antibacterial and anti-inflammatory performance

Abstract

This study describes the construction of a tailor-made clay-based hybrid with advanced dermocompatibility, antibacterial and anti-inflammatory performance by incorporating tunable ratios of tea tree oil (TTO) and salicylic acid (SA) into the naturally occurring porous structure of palygorskite (Pal). Among the three TTO/SA/Pal (TSP) systems constructed, TSP-1 with a TTO : SA ratio of 1 : 3 demonstrated the lowest 3T3 NRU predicted acute oral toxicity and dermal HaCaT cytotoxicity as well as the most pronounced antibacterial activity with a selective inhibitory action against the pathogens (<i>E. coli</i>, <i>P. acnes</i> and <i>S. aureus</i>) over the beneficial (<i>S. epdermidis</i>) species inhabiting on the human skin. Also noticeable is that exposure of these skin commensal bacteria to TSP-1 prevented the antimicrobial resistance evolution compared to the conventional antibiotic ciprofloxacin. Mechanistic investigation of its antibacterial modes of action revealed a synergy between the TTO and SA loadings on the Pal supports in reactive oxygen production, causing oxidative damage to bacterial cell membranes and increased leakage of intracellular compounds. Additionally, TSP-1 significantly decreased the proinflammatory cytokines of IL-1β, IL-6, IL-8, and TNF-α in a bacterial lipopolysaccharide-stimulated differentiated THP-1 macrophage model, showing the potential to inhibit inflammatory responses in bacterial infections. Overall, this is the first report exploring the potential of constructing clay-based organic-inorganic hybrids as alternatives to antibiotics to combat bacterial resistance with advanced compatibility and anti-inflammatory benefits that are desired for the development of topically applied biopharmaceuticals.