Development of thymol-loaded biocompatible PLA/PLGA composite nanoparticles for oral health care application: Antimicrobial and antibiofilm activities

Thymol-loaded PLA, PLGA, and PLA-PLGA nanoparticles were fabricated for oral care applications. • Nanoparticles achieved sustained thymol release with enhanced antimicrobial and antibiofilm activity. • Nanoparticle encapsulation enhanced thymol-induced microbial membrane damage. • The PLA-PLGA formulation balanced high cytocompatibility and low hemolysis without compromising antimicrobial efficacy. Biocompatible nanoformulations offer a promising approach to enhancing the bioavailability and bioactivity of phytochemicals such as thymol, thereby expanding their potential for oral healthcare applications. This study fabricated thymol-loaded polylactic acid (PLA), poly (lactic- co -glycolic acid) (PLGA), and PLA-PLGA blend nanoparticles through single-emulsion solvent evaporation, and compared their physicochemical properties, antimicrobial activity, and preliminary biological safety comprehensively. All nanoparticles exhibited a spherical and uniform morphology, while increasing the PLGA content resulted in a slightly more porous surface structure. Thymol release from all formulations followed a biphasic release profile, with PLGA nanoparticles showing the highest encapsulation efficiency and the fastest release. In contrast, PLA-PLGA blend nanoparticles provided more sustained thymol release, leading to prolonged antimicrobial and antibiofilm activities against the oral wound-associated pathogens Escherichia coli and Staphylococcus aureus , as well as the major oral microorganisms Streptococcus mutans and Candida albicans . Fluorescence staining and SEM observations demonstrated that nanoparticle encapsulation enhanced thymol-induced membrane permeabilization and structural damage to microbial cells. At an equivalent thymol concentration, PLA-PLGA blend nanoparticles maintained approximately 95% cell viability and caused less than 5% hemolysis without compromising antimicrobial efficacy, supporting their further development for local oral infection control. Download: Download high-res image (275KB) Download: Download full-size image