Dual-drug delivery of sodium ceftriaxone and metronidazole by applying salt-assisted chitosan nanoparticles: Stability, drug release, and time-kill assay study against Bacteroides fragilis

摘要

The purpose of this study was to develop a polymeric biomaterial with regulated dual drug release and increased bactericidal strength of the antibiotics sodium ceftriaxone (CTX) and metronidazole (MTZ) for the treatment of intra-abdominal infections. Chitosan nanoparticles (CS NPs) were produced by ionic crosslinking process in the presence of NaCl monovalence salt. The antibacterial activity and drug release behavior of CS NPs were investigated against anaerobic Bacteroides fragilis. The optimum initial drug ratio for designing dual drug carriers containing CTX and MTZ in a 4:3 ratio was 1:1. After 6 months, the salt-assisted CTX-MTZ-loaded CS NPs were 300 nm in size and had a polydispersity index of 0.09 with high stability. It has been demonstrated that drug release from NPs is more tightly controlled than drug release from free drugs. Furthermore, the data show that the minimum inhibitory concentration and minimum bactericidal concentration for nanostructure carriers are one-quarter of those of free medicines. Free drugs could completely kill the bacterium after 24 h, but the dual drug carrier could kill the bacteria in 10 h. Finally, salt-assisted CTX-MTZ-loaded CS NPs were proposed as a feasible alternative to standard intra-abdominal infection treatment.