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

Abstract

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.

Immobilization of Olive Leaf Extract with Chitosan Nanoparticles as an Adjunct to Enhance Cytotoxicity

“…Accordingly, chitosan nanoparticles have been used to release two antibiotics (metronidazole and sodium ceftriaxone) and to increase the bactericidal strength for the treatment of intraabdominal infections. 14 In addition, a carboxymethyl chitosan-coated poly(lactide-co-glycolide) (cmcPLGA) core−shell nanostructure caused strong inhibition, even at low concentrations, of A549 (lung adenocarcinoma), PC3 (prostate cancer), and BT549 (breast ductal carcinoma) cell lines. 15 Olea europaea, the olive tree, has held an important place in the herbal medicine of Mediterranean and European countries for many years.…”

“…Also, it possesses some beneficial properties (e.g., high stability, biological degradability, and sufficient permeability), which enable the use of chitosan as an ideal biological polymer in medical applications. , There have been some recent reports on the use of chitosan-derived nanomaterials in medicine. Accordingly, chitosan nanoparticles have been used to release two antibiotics (metronidazole and sodium ceftriaxone) and to increase the bactericidal strength for the treatment of intra-abdominal infections . In addition, a carboxymethyl chitosan-coated poly­(lactide- co -glycolide) (cmcPLGA) core–shell nanostructure caused strong inhibition, even at low concentrations, of A549 (lung adenocarcinoma), PC3 (prostate cancer), and BT549 (breast ductal carcinoma) cell lines …”