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<p>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 <i>Escherichia coli</i> 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 <i>Icam-1</i> and <i>Tnf-α</i> 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.</p>

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Enrofloxacin-loaded Zein nanoparticles combat E. coli O157:H7 in biomimetic 3D intestinal model

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月1日

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  • Genesis J. Herrera,
  • Nedrick T. Distor,
  • Lurima U. Faria,
  • Janire Peña-Bahamonde,
  • Hoang Nguyen,
  • Debora F. Rodrigues

摘要

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.