Home Science Viral surface-inspired nanocarriers for improved oral insulin therapy

Viral surface-inspired nanocarriers for improved oral insulin therapy

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Nature Communications (2022). DOI: 10.1038/s41467-022-34357-8″ width=”800″ height=”530″/>

Schematic representation of the composition and mechanism of Pep/Gal-PNPs for oral insulin delivery. a Construction of viral surface-inspired ligand-switchable nanoparticles (Pep/Gal-PNPs) modified with both pH-triggered stretchable cell-permeable peptides (Pep) and liver-targeting moieties (galactose, Gal) . b After oral administration, Pep adopts a stretched conformation in response to the acidic environment in the intestine and mediates efficient Pep/Gal-PNP transport across the intestinal barrier. Gal is subsequently exposed to the surface as Pep folds at physiological pH in circulation and induces Pep/Gal-PNP specifically to the liver. credit: Nature Communications (2022). DOI: 10.1038/s41467-022-34357-8

Clinically, patients with type 1 diabetes (T1DM) and advanced type 2 diabetes (T2DM) require multiple daily insulin injections to maintain blood glucose levels. In comparison, oral insulin therapy has high patient compliance.

There are two bottlenecks to achieving desirable oral insulin therapy. One is the gastrointestinal barrier, which severely limits oral absorption of insulin. The second is the inadequate accumulation of insulin at target sites after absorption. Under physiological conditions, the liver is exposed to insulin levels two to three times higher than the periphery and processes almost one-third of the ingested glucose. Oral insulin delivery should therefore stepwise cross the intestinal mucosal barrier and specifically target the liver, thus simulating the biodistribution of endogenous insulin and ultimately improving blood glucose utilization. .

In a study published in Nature Communicationsa team led by Professor Gan Yong of the Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences, in collaboration with Professor Wei Gang of Fudan University, reported a multifunctional nanocarrier resembling a viral surface for oral insulin therapy.

The researchers designed ligand-switchable nanoparticles modified with a pH-responsive stretchable cell-permeable peptide (Pep) and a liver-targeting moiety (Gal) (Pep/Gal-PNPs). When administered orally, an acidic environment triggers elongation of Pep from the surface in a virus-like manner, allowing Pep/Gal-PNP to efficiently cross the intestinal barrier. Gal was then exposed by Pep folding at physiological pH, which enabled specific targeting of Pep/Gal-PNP to the liver.

In vivo results showed that Pep/Gal-PNPs exhibited efficient intestinal absorption and excellent hepatic deposition (accounting for 79.1% of total absorption). Moreover, her Pep/Gal-PNPs loaded with insulin showed significant hypoglycemic effects in type 1 diabetic rats. Importantly, they increased liver glycogen production 7.2-fold and improved glucose metabolism.

This study provides a new oral insulin Efficiently overcome the intestinal mucosal barrier and accurately liver By mimicking the unique surface features and functions of the virus, it achieves rational handling of blood sugar in diabetes and contributes to blood maintenance glucose homeostasis.

For more information:
Tiantian Yang et al., Viral surface-like ligand-switchable nanoparticles for sequential drug delivery and improved oral insulin therapy. Nature Communications (2022). DOI: 10.1038/s41467-022-34357-8

Quote: Viral Surface-Inspired Nanocarriers for Improved Oral Insulin Therapy (December 2, 2022)

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