Oral peptide or protein delivery is considered as a revolutionary alternative to daily subcutaneous injection; However, there are still major challenges in the gastrointestinal environment and the barrier of the intestinal epithelium, which is composed of mucus and epithelial cell layers, leading to low bioavailability.

In order to prevent gastrointestinal degradation and promote penetration through intestinal mucosa, Chen Xuesi, academician of Changchun Institute of Applied Chemistry, China Academy of Sciences and He Chaoliang et al. Have designed a pH triggered self unwrapping capsule encapsulating zwitterionic hydrogel coated metal organic frameworks (MOF) nanoparticles.

Key points of this paper

1) MOF nanoparticles possess high drug loading efficiency of exendin-4, and the zwitterionic hydrogel layer has unique permeability to the mucus layer and the effective internalization ability of epithelial cells to nano carriers.

2) In addition to gastric tolerance, due to the rapid generation of a large number of carbon dioxide bubbles, pH responsive capsules are rapidly separated in the intestinal environment, triggering the sudden release of nanoparticles. After oral administration of capsules containing exendin-4 nanoparticles into diabetic rats, the level of plasma Exendin-4 increased significantly for more than 8 hours, resulting in a significant increase in endogenous insulin secretion and a significant hypoglycemic effect, with a relative pharmacological utilization rate of 17.3%. Because of the low risk of hypoglycemia, the oral exendin-4 strategy will provide great potential for daily and simple diabetes treatment.

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