Antimicrobial resistance in enteric pathogens demands biotechnology-enabled strategies that enhance the efficacy of oral antibiotics while mitigating toxicity and resistance selection. Preclinical evaluation is hindered by reliance on animal models and two-dimensional (2D) cultures that incompletely recapitulate human intestinal architecture, mucus barriers, and infection dynamics. Here, a three-dimensional (3D) villus-mimetic intestinal model based on polydopamine-coated polydimethylsiloxane scaffolds was established as a biomimetic platform to assess advanced nanoparticle-antibiotic drug delivery systems. Zein nanoparticles were formulated into biodegradable carriers encapsulating the fluoroquinolone Enrofloxacin and tested in porcine IPEC-J2 epithelial cells infected with enteropathogenic Escherichia coli O157:H7. Enrofloxacin-loaded Zein carriers achieved the greatest reduction in bacterial burden across both 2D and 3D cultures at a biocompatible dose compared with free drug and empty carriers, indicating improved antimicrobial performance. The 3D scaffolds promoted enhanced epithelial differentiation and mucin production and showed a trend toward lower Icam-1 and Tnf-α induction after infection and treatment relative to 2D monolayers, suggesting a more physiologic mucosal and inflammatory profile. These data position the 3D villus-mimetic system as an integrated biotechnology platform that links infection biology, epithelial function, and drug delivery performance in a single assay. The approach offers a scalable route to preclinical screening of protein-based oral antibiotic carriers and other biotechnology-driven interventions targeting intestinal infections and antimicrobial resistance.
Herrera et al. (Mon,) studied this question.