Oral Drug Delivery Systems for Biopharmaceuticals

Oral administration remains the most convenient route for the delivery of biopharmaceuticals, combining ease of use with broad patient acceptance and cost-effective manufacturing. However, large molecules such as peptides and proteins face multiple barriers in the gastrointestinal tract, including enzymatic degradation, low epithelial permeability and heterogeneous pH environments. To surmount these challenges, advanced delivery systems harness strategies such as protease inhibition, mucoadhesive platforms, nanocarrier encapsulation and targeted release at specific intestinal segments. Recent innovations draw inspiration from biological architectures, deploying bioinspired materials or living microorganisms to shield therapeutic payloads, prolong residence time and promote translocation across the mucosal barrier. Collectively, these approaches aim to improve systemic bioavailability, reduce dosing frequency and extend the range of molecules amenable to oral dosing, with profound implications for chronic disease management, vaccination programmes and global access to injectable-grade therapies.

Research from Nature Portfolio

Recent studies have devised bioinspired oral delivery devices that mimic natural structures and functions to overcome digestive tract obstacles. By integrating components derived from bacterial cell walls, polysaccharide matrices and shape-memory polymers, these devices can transiently adhere to the intestinal mucosa, protect against enzymatic degradation and achieve programmable, site-specific release of payloads. Engineering strategies focus on dynamic responsiveness to pH gradients and targeted interaction with M-cells or Peyer’s patches, enhancing cellular uptake. Preclinical assessments reveal robust protection of sensitive proteins in simulated gastric fluids and improved systemic absorption in large-animal models, marking a significant step towards clinical translation of oral biopharmaceutical formulations.

Oral Drug Delivery Systems for Biopharmaceuticals publication trend

The graph below shows the total number of articles in oral drug delivery systems for biopharmaceuticals across all publications each year (not limited to Nature Index journals).

Technical terms

Biopharmaceuticals: Therapeutic proteins, peptides and nucleic acids produced by biological sources.

Permeation enhancers: Agents that transiently increase intestinal epithelial permeability to improve drug uptake.

Mucoadhesion: The property of a material to adhere to mucosal surfaces, prolonging residence time.

Bioinspired devices: Delivery systems designed by imitating natural structures or biological processes.

Nanocarriers: Nanoscale vehicles (e.g., liposomes, polymeric nanoparticles) used to encapsulate and protect cargo.

References

1. Bioinspired oral delivery devices. Nature Reviews Bioengineering (2023).
2. Safety of surfactant excipients in oral drug formulations. Advanced Drug Delivery Reviews (2023).
3. Gastrointestinal Permeation Enhancers Beyond Sodium Caprate and SNAC ‐ What is Coming Next?. Advanced Science (2024).
4. Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals. Pharmaceutics (2019).
5. Advances in Oral Drug Delivery for Regional Targeting in the Gastrointestinal Tract - Influence of Physiological, Pathophysiological and Pharmaceutical Factors. Frontiers in Pharmacology (2020).