RESUMEN
Polymeric nanomaterials (APs) are gaining attention as promising clinical antimicrobials with rapidly increasing antibiotic resistance. Infections by zoonotic enterohemorrhagic Escherichia coli are a severe global threat to public health. Chitosan nanoparticles-microcin J25 (CNM), a class of APs engineered by bioactive peptides and chitosan nanoparticles, can be used as a novel antimicrobial agent against bacterial infections. However, the risk assessment of CNM on animal health or its potential immune modulation to treat serotype E. coli O157:H7 infection impacts in vivo are not well understood. Herein, our findings in mouse models uncovered that oral administration of low levels of CNM significantly increased the body weight and made beneficial effects on the lifespan or clinical signs, accompanied by a significant improvement in gut health, including enhancing the intestinal barrier, immune modulation, and changes in gut microbiota compositions or metabolites. However, high concentrations of CNM induced serious adverse effects, negatively improving intestinal health targets. Anti-infective results proved that oral 0.1% CNM enhances host defense against E. coli O157:H7 infection by improving immune functions and modulating the Th1/Th2 balance. In summary, these findings uncover an instrumental link between the dosage and toxicity risk, suggesting that APs need to be comprehensively assessed for risk before application as safe and reliable food preservatives or therapeutic agents. In addition, CNM as a promising AP may markedly enhance host immunity and therapeutic effects by oral administration.
Asunto(s)
Antiinfecciosos , Quitosano , Infecciones por Escherichia coli , Escherichia coli O157 , Nanopartículas , Animales , Antiinfecciosos/farmacología , Péptidos Antimicrobianos , Quitosano/química , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Conservantes de Alimentos/farmacología , Ratones , Nanopartículas/química , Medición de RiesgoRESUMEN
This investigation evaluated the adsorption behavior of the antiviral drugs of oseltamivir (OE) and its metabolites (i.e., oseltamivir carboxylate (OC)) on three types of carbon nanotubes (CNTs) including single-walled CNT (SWCNT), multi-walled CNT (MWCNT), and carboxylated SWCNT (SWCNT-COOH). CNTs can efficiently remove more than 90% of the OE and OC from aqueous solution when the initial concentration was lower than 10(-4) mmol/L. The Polanyi-Manes model depicted the adsorption isotherms of OE and OC on CNTs better than the Langmuir and Freundlich models. The properties of OE/OC and the characteristics of CNTs, particularly the oxygen functional groups (e.g., SWCNT-COOH) played important roles during the adsorption processes. OE showed a higher adsorption affinity than OC. By comparing the different adsorbates adsorption on each CNT and each adsorbate adsorption on different CNTs, the adsorption mechanisms of hydrophobic interaction, electrostatic interaction, van der Waals force, and H-bonding were proposed as the contributing factors for OE and OC adsorption on CNTs. Particularly, for verifying the contribution of electrostatic interaction, the changes of adsorption partition efficiency (Kd) of OE and OC on CNTs were evaluated by varying pH from 2 to 11 and the importance of isoelectric point (pHIEP) of CNTs on OE and OC adsorption was addressed.