Prevention of infection caused by enteropathogenic E. coli O157:H7 in intestinal cells using enrofloxacin entrapped in polymer based nanocarriers

Abstract

Poor bioavailability of antibiotics, toxicity, and development of antibiotic-resistant bacteria jeopardize antibiotic treatments. To circumvent these issues, drug delivery using nanocarriers are highlighted to secure the future of antibiotic treatments. This work investigated application of nanocarriers, to prevent and treat bacterial infection, presenting minimal toxicity to the IPEC-J2 cell line. To accomplish this, polymer-based nanoparticles (NPs) of poly(lactide-co-glycolide) (PLGA) and lignin-graft-PLGA (LNP) loaded with enrofloxacin (ENFLX) were synthesized, yielding spherical particles with average sizes of 111.8 ± 0.6 nm (PLGA) and 117.4 ± 0.9 nm (LNP). The releases of ENFLX from PLGA and LNP were modeled by a theoretical diffusion model considering both the NP and dialysis diffusion barriers for drug release. Biocompatible concentrations of ENFLX, enrofloxacin loaded PLGA(Enflx) and LNP(Enflx) were determined based on examination of bacterial inhibition, toxicity, and ROS generation. Biocompatible concentrations were used for treatment of higher- and lower-level infections in IPEC-J2 cells. Prevention of bacterial infection by LNP(Enflx) was enhanced more than 50% compared to ENFLX at lower-level infection. At higher-level infection, PLGA(Enflx) and LNP(Enflx) demonstrated 25% higher prevention of bacteria growth compared to ENFLX alone. The superior treatment achieved by the nanocarried drug is accredited to particle uptake by endocytosis and slow release of the drug intracellularly, preventing rapid bacterial growth inside the cells.