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


METHODS
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.


CONCLUSIONS
The synergistic effect of ceftriaxone-loaded CNPs is a useful finding for the treatment of MRSA and E. coli infections.
Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
Sana
S
Mushtaq
Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
Jawad Akbar
JA
Khan
Department of Environmental Sciences, COMSATS Institute of Information Technology, Vehari, Pakistan.
Faiz
F
Rabbani
Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore, Pakistan.
Usman
U
Latif
Department of Chemistry, School of Natural Sciences, National University of Sciences and Technology, H-12, Islamabad, Pakistan.
Muhammad
M
Arfan
Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
Muhammad Arfat
MA
Yameen
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D002443:Ceftriaxone / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D009503:Neutropenia; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D002443:Ceftriaxone; D048271:Chitosan