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Frontiers in Pharmacology· 2026Q1· Review

Microbiome-aware oral drug delivery: excipient–microbiome interactions and nanocarrier design rules for predictable formulation performance

mohamed sedeek, Ahmed Ayoub, Essam Hany, Ahmed Bahaa et al.

Short summary

A new framework is proposed for oral drug delivery that systematically accounts for gut microbiome interactions, offering design rules for nanocarriers and excipients to improve formulation predictability.

AI-generated from the title and abstract; the full text is not read.

Key points

  • The gut microbiome can alter drug metabolism, excipient behavior, and nanocarrier interactions, leading to interpatient variability.
  • Microbial metabolism examples include digoxin inactivation by Eggerthella lenta and levodopa metabolism.
  • Excipients like certain polysaccharides, surfactants, and polymers can pose context-dependent microbiome or barrier risks.
  • Nanocarrier design variables such as size, charge, coating, and biodegradability are critical microbiome-interface factors.
  • A proposed framework offers excipient classification, nanocarrier design rules, and a testing roadmap for predictable formulation development.

AI-generated from the title and abstract; the full text is not read.

Abstract

Oral drug delivery remains the predominant administration route, but formulation strategies rarely account systematically for the gut microbiome. The microbiome can alter drug metabolism, excipient behavior, nanocarrier interactions, and interpatient variability. This review integrates evidence on microbial drug metabolism, excipient–microbiome interactions, nanocarrier engineering, microbiota-responsive delivery, and experimental models. Clinically relevant examples include digoxin inactivation by Eggerthella lenta , bacterial levodopa metabolism, and microbial beta-glucuronidase-mediated irinotecan toxicity. Microbiota-degradable polysaccharides may serve as colon-targeted release triggers, whereas some surfactants and polymers may create context-dependent microbiome or barrier risks. Nanocarrier size, charge, coating, mucoadhesion, mucus penetration, biodegradability, enzyme responsiveness, and surfactant burden are treated as microbiome-interface variables. We propose an authors’ evidence-informed framework comprising an excipient classification, nanocarrier design rules, microbiota-responsive decision logic, and a tiered testing roadmap. These proposals are not established regulatory classifications; they are intended to support more predictable and patient-relevant oral formulation development.

The authors' abstract, as published at the source. Frontiers in Pharmacology, 2026 · DOI ↗

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Field: Pharmaceutical Science

Pharmaceutical SciencePharmacology, Toxicology and Pharmaceutics