Nanoparticle-Based Oral Insulin Delivery Systems

The oral delivery of insulin via nanocarriers aims to overcome the limitations of subcutaneous injections by protecting the peptide from enzymatic degradation, navigating the harsh gastrointestinal environment and achieving controlled release. Nanoparticle-based systems leverage their tunable size, surface chemistry and composition to enhance mucosal permeation and mucoadhesion, prolong intestinal residence time and respond to local stimuli such as pH and glucose concentrations. Key strategies include the use of biocompatible polymers (e.g. chitosan, alginate, PLGA), lipid-based carriers and inorganic quantum dots, often functionalised with targeting ligands or responsive moieties. Recent progress has demonstrated insulin-conjugated nanoparticles that remain intact under acidic stomach conditions but dissolve at neutral intestinal pH, optimising absorption. Glucose-responsive platforms employ chemical groups or enzymes that trigger insulin release in response to hyperglycaemia, limiting the risk of hypoglycaemia. Together, these approaches hold promise for a patient-friendly, physiologically mimetic therapy with improved glycaemic control and enhanced quality of life for people with diabetes.

Research from Nature Portfolio

Recent studies have demonstrated an oral nanoformulation comprising insulin-conjugated semiconductor quantum dots coated with a chitosan–glucose polymer that remains insoluble in acidic gastric fluid and disassembles at neutral pH. This construct shows enhanced permeation across human intestinal explants, enzyme-triggered release in response to glucosidases and a dose-dependent reduction in blood glucose in diabetic rodents and non-human primates without causing hypoglycaemia or observable toxicity. The work highlights the integration of responsive inorganic cores with biopolymer coatings to achieve safe, effective and controlled oral insulin delivery.

Nanoparticle-Based Oral Insulin Delivery Systems publication trend

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

Technical terms

Nanoparticle: A particle between 1 and 100 nm in size used to carry therapeutic agents.

Bioavailability: The proportion of an administered dose that reaches systemic circulation.

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

pH-responsive: A material that changes properties or disassembles in response to local pH variations.

Glucose-responsive: A system designed to release insulin in response to elevated glucose concentrations.

References

1. Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycaemia. Nature Nanotechnology (2024).
2. An Engineered Nanosugar Enables Rapid and Sustained Glucose‐Responsive Insulin Delivery in Diabetic Mice. Advanced Materials (2023).
3. Helical‐Like Assembly of Nateglinide as Coating for Oral Delivery of Insulin and Their Synergistic Prevention of Diabetes Mellitus. Advanced Science (2023).
4. Polymeric nanoparticles (PNPs) for oral delivery of insulin. Journal of Nanobiotechnology (2024).