Nanoparticle-Mediated Oral Drug Delivery Systems

The oral route remains the most patient-friendly means of administering therapeutics, yet it is hindered by enzymatic degradation, acidic pH, mucus entrapment and poor epithelial permeability. Nanoparticle-mediated delivery systems address these barriers by encapsulating active agents within biocompatible carriers—lipid, polymeric or inorganic—that protect cargo from harsh luminal conditions while promoting targeted uptake. Surface functionalisation with ligands or stealth polymers can enhance mucoadhesion or facilitate receptor-mediated endocytosis, whereas stimuli-responsive designs allow controlled release in response to pH shifts, redox gradients or enzymatic cues. Advances in mesoporous matrices, hydrophilic coatings and chiral or virus-mimicking topologies have further improved intestinal traversal and lymphatic uptake. By tailoring size, charge and surface chemistry, researchers have achieved sustained release of peptides, proteins and small molecules, elevating oral bioavailability into clinically relevant ranges. Collectively, these platforms not only broaden the therapeutic scope of orally delivered biologics but also hold promise for decentralised care in chronic diseases such as diabetes, hypertension and inflammatory disorders.

Research from Nature Portfolio

Researchers have designed core–shell silica nanoparticles bearing virus-inspired nanospikes and chiral amino-acid modifications, which mimic viral adhesion to overcome sequential intestinal barriers. These particles demonstrated enhanced muco-penetration, multivalent anchoring to mucosal cells and improved absorption of anti-inflammatory payloads in preclinical models. In parallel, Fc-conjugated polymeric nanoparticles have been developed for oral delivery of peptide drugs; Fc fragments facilitate neonatal Fc receptor-mediated transcytosis, extending gastrointestinal residence time and yielding prolonged hypoglycaemic effects in animal studies. Foundational work with chitosan-based nanocapsules has shown that encapsulation of tight-junction modulators can reversibly open epithelial barriers, increasing paracellular transport of macromolecular cargo without compromising cell viability. Together, these studies illustrate how biomimetic surface architectures, receptor targeting and controlled barrier modulation can converge to elevate oral delivery of therapeutics.

Nanoparticle-Mediated Oral Drug Delivery Systems publication trend

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

Technical terms

Oral bioavailability: Fraction of administered dose reaching systemic circulation.

Paracellular transport: Passage of substances between adjacent epithelial cells.

Transcytosis: Cellular process of uptake, vesicular transport and release on the opposite membrane.

Stimuli-responsive nanoparticles: Carriers engineered to release cargo upon specific environmental triggers.

Mesoporous silica nanoparticles: Inorganic particles with tunable pore structures for high drug loading.

Surface functionalisation: Chemical modification of nanoparticle exterior to confer targeting or stealth properties.

References

1. Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme-Induced Proximity Labeling. Nano-Micro Letters (2024).
2. Nanoparticles exhibiting virus-mimic surface topology for enhanced oral delivery. Nature Communications (2023).
3. pH and H2O2 dual-sensitive nanoparticles enable enhanced and safe glucose-responsive oral insulin delivery for diabetes mellitus treatment. Theranostics (2024).
4. The challenges of oral drug delivery via nanocarriers. Drug Delivery (2018).
5. Research on the fate of polymeric nanoparticles in the process of the intestinal absorption based on model nanoparticles with various characteristics: size, surface charge and pro-hydrophobics. Journal of Nanobiotechnology (2021).
6. Chitosan encapsulation modulates the effect of capsaicin on the tight junctions of MDCK cells. Scientific Reports (2015).
7. Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice. Scientific Reports (2018).