Biocompatible Biodegradable Polymeric Antibacterial Nanoparticles for Enhancing the Effects of a Third-Generation Cephalosporin Against Resistant Bacteria

Purpose. In the present study, enhancement of the the antibacterial activity of ceftriaxone against Gram-positive (meticillin-resistant Staphylococcus aureus; MRSA) and Gram-negative (Escherichia coli) bacteria with a biodegradable polymer was attempted.Methodology. MRSA and E. coli were collected and identified by biochemical and molecular tests. Blank and ceftriaxone-loaded chitosan nanoparticles (CNPs) were prepared by the ionic gelation method. In vitro antibiotic-susceptibility studies were performed by disc diffusion, agar well plate method, Etest and time-kill assay. In vivo activity was assessed using the neutropenic mouse thigh model and cytotoxicity was estimated by MTT (methylthiazolyldiphenyl tetrazolium bromide) assay with the MCF-7 cancer cell line.Results. MRSA showed 97% and E. coli 83% resistance against ceftriaxone in the disc diffusion test. The isolates showing a >= 1024 mg l(-1) MIC value for ceftriaxone were selected for further evaluation. In the agar well plate method, the mean zones of inhibition for blank and ceftriaxone-loaded CNPs were 17 and 23 mm, respectively, for MRSA isolates and 15 and 25 mm, respectively, for E. coli isolates. In the time-kill assay, similar to 1 log(10) to similar to 2.5 log(10) reduction in viability was seen with both isolates when treated with ceftriaxone-loaded CNPs over 24 h. The in vivo studies also showed the enhanced antibacterial activity of ceftriaxone-loaded CNPs, with a 41% reduction in MRSA and a 27% reduction in E. coli burden. A low cytotoxicity of blank and ceftriaxone-loaded CNPs was seen, with a slight reduction in the percentage viability of cells from 87 to 83% and from 88 to 81 %, respectively.Conclusion. The synergistic effect of ceftriaxone-loaded CNPs is a useful finding for the treatment of MRSA and E. coli infections.