Polymer-Based Nanocarriers to Treat Intestinal Infection and Reduce Impact on Gut Microbiome

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Nanomaterials have garnered huge attention for biomedical applications due to their extraordinary physio-chemical and biological properties. The current study presents the synthesis and characterization of polymer-based nanoparticles (NPs) of Poly(lactic-co-glycolic acid) (PLGA) and lignin-graft-PLGA (LNP) loaded with the antibiotic enrofloxacin. The synthesized nanoparticles for both PLGA and LNP presented spherical shape with average diameter of 112 and 117 nm respectively. The entrapment of enrofloxacin in the nanoparticle matrix improved and sustained the release of the antibiotic. Furthermore, the encapsulation of enrofloxacin led to minimization of reactive oxygen species (ROS) production from the free drug form, which has been established to be toxic to mammalian cells. The biocompatible concentration of free dugs and polymeric nanoparticles was further investigated for the treatment of pathogenic bacterial infection in the intestinal pig cell line. The biocompatible concentration of the drug loaded nanoparticles was based on the examination of bacterial inhibition, toxicity, and ROS generation results and were found to be 0.18 μg/ml for enrofloxacin drug loaded PLGA nanoparticles and 0.20 μg/ml for enrofloxacin drug loaded LNP nanoparticles. The biocompatible concentrations of the two nanoparticles, as well as the free drug, were used to treat bacterial infection at higher and lower levels of infections. The nano delivered antibiotic demonstrated better performance in treating infected cells at all time points and provided at least 50% higher treatment efficacy compared to the free antibiotic. The superior treatment achieved by the nano carried drug delivery systems is accredited to particle uptake by endocytosis and slow release of the drug intracellularly, preventing rapid bacterial growth inside the cells. The infection treatment efficacy of nano carried drug is not sufficient for their commercial use. The understanding of interaction and effects of nanocarriers for drug release on gut microbial systems is also very important because gut microbial health has important effects on human and animal health. Thus, this study also focused on the effects of drug-loaded nanocarriers in the pig gut microbial system. The result demonstrated biodegradable nanomaterials for drug delivery is highly beneficial in preserving the core microbiome of the gut. The empty PLGA and LNP nanoparticles demonstrated minimal microbial community change indicating inert effects of the nanoparticles on the core microbial community. The enrofloxacin drug loaded LNP demonstrated significant change in microbial community due to the drug effect. This study indicates that that enrofloxacin loaded nanoparticles can be used for antimicrobial drug delivery, infection treatment and prevention. Depending on the material of choice, this approach can treat bacterial infection and still preserve the core microbial community to maintain homeostasis.

Nanoparticles, Polymer
Portions of this document appear in: Paudel, Sachin, Constantin Cerbu, Carlos E. Astete, Stacey M. Louie, Cristina Sabliov, and Debora F. Rodrigues. "Enrofloxacin-impregnated PLGA nanocarriers for efficient therapeutics and diminished generation of reactive oxygen species." ACS Applied Nano Materials 2, no. 8 (2019): 5035-5043; and in: Paudel, Sachin, Janire Peña-Bahamonde, Sheyda Shakiba, Carlos E. Astete, Stacey M. Louie, Cristina M. Sabliov, and Debora F. Rodrigues. "Prevention of infection caused by enteropathogenic E. coli O157: H7 in intestinal cells using enrofloxacin entrapped in polymer based nanocarriers." Journal of Hazardous Materials 414 (2021): 125454.