Niosome-embedded in situ gels for root canal irrigation: Preparation and optimization of a composite system for chlorhexidine delivery

Niosomes could increase the efficacy of the irrigants by providing a controlled drug release. Incorporating niosomes into an in situ gel matrix maximizes the drug retention time in the root canal system. The focus of this study was the fabrication and characterization of a niosomal in situ gel system for delivering chlorhexidine to root canals. For this aim, chlorhexidine-loaded niosomes were optimized by evaluating the impacts of surfactant type, surfactant to cholesterol ratio, lipid to drug weight ratio, and ethanol concentration on particle size and entrapment efficiency (EE) using an experimental design. The in situ gels were also optimized with the aid of an experimental design by identifying the effects of chitosan and beta-glycerophosphate concentrations as well as the solution stirring time on the gelation time and gelation temperature. The optimum niosomal nanoformulation showed an average particle size of 115 nm, EE% of similar to 80 %, and PDI of 0.1. The optimum in situ gels showed the lowest gelation time and appropriate gelation temperature (60 s and 29 degrees C, respectively). The in vitro release studies showed that niosomal in situ gels successfully sustained the release of similar to 97 % of chlorhexidine over 144 h with Higuchi kinetics. Furthermore, the biological evaluations revealed that the niosomal in situ gels were cytocompatible. The system also exhibited antibacterial activity against Enterococcus faecalis bacteria, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans by respectively showing 18.0, 33.3, and 48.3 mm inhibition zones in the agar well diffusion test. Overall, the results indicated that niosome-embedded in situ gels showed promising potential for antimicrobial delivery to root canals.