Zein Nanoparticles for Controlled Intestinal Drug Release for the Treatment of Gastrointestinal Infections

Plant-based polymers, as nanodrug delivery systems (NDDS), offer many benefits over synthetic ones. Optimizing the interactions of the entrapped drug within the NDDS material, loading capacity, transport behavior, physicochemical transformations, and drug release under realistic physiological conditions is crucial to ensure the appropriate application of NDDS. In this work, NDDS composed of Zein nanoparticles with tuned hydrophobicity were synthesized by nanoprecipitation. Hydrophobicity was modified by increasing or decreasing the -COOH groups or adding succinyl groups. The nanoparticles were loaded with the most used antibiotics, i.e., enrofloxacin, ciprofloxacin, metronidazole, nitrofurantoin, and norfloxacin, to target intestinal infections caused by Escherichia coli and Salmonella typhimurium. The drug release of the synthesized NDDS was evaluated under simulated gastrointestinal conditions, i.e., simulating mouth, stomach, and intestine conditions. The results showed that more hydrophilic drugs (norfloxacin and nitrofurantoin) exhibited higher release (similar to 75 and similar to 65% respectively) in intestinal conditions where gastrointestinal infections occur. Moreover, adding more carboxylic groups to the nanoparticles played an essential role in controlling the release of the drug in the target treatment site, the intestine. Further investigation of the antimicrobial properties of the NDDS revealed synergistic activity between the Zein nanoparticles (modified and unmodified) and ciprofloxacin, enrofloxacin, or nitrofurantoin against antibiotic-resistant E. coli O157:H7 and S. typhimurium. The antibiotic loaded into Zein nanoparticles improved the bacterial inactivation by lowering the antibiotic concentration (0.13 mg/mL for enrofloxacin and ciprofloxacin and 80 mg/mL for nitrofurantoin) needed to inactivate 90% of both antibiotic-resistant strains. These findings provide insights into the potential of plant-based polymer NDDS for drug delivery and highlight the importance of optimizing the loading capacity and tailoring the chemical structure of the polymer to improve drug delivery in the target tissue and combat antibiotic-resistant microorganisms.