Biocompatible biodegradable polymeric antibacterial nanoparticles for enhancing the effects of a third-generation cephalosporin against resistant bacteria

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Abstract

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, ˜1 log10 to ˜2.5 log10 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.

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