Acid-Resistant Mesoporous Metal-Organic Frameworks as Carriers for Targeted Hypoglycemic Peptide Delivery: Peptide Encapsulation, Release, and Bioactivity

Oral administration of bioactive peptides with alpha- glucosidase inhibitory activities is a promising strategy for diabetes mellitus. The wheat germ peptide Leu-Asp-Leu-Gln-Arg (LDLQR) has been previously proven to inhibit the activity of alpha-glucosidase efficiently. However, it is still difficult to transport the peptide to the intestine completely due to the harsh condition of the stomach. Herein, an acid-resistant zirconium-based metal- organic framework, NU-1000, was used to immobilize LDLQR with a high encapsulation capacity (92.72%) and encapsulation efficiency (44.08%) in only 10 min. The in vitro release results showed that the acid-stable NU-1000 not only effectively protected LDLQR from degradation in the presence of stomach acid and pepsin effectively but also ensured the release of encapsulated LDLQR under simulated intestinal conditions. Furthermore, LDLQR@NU-1000 could slow down the elevated blood sugar caused by maltose in mice and the area under blood sugar curve decreased by almost 20% when compared with the control group. The inflammatory factor (IL-1 beta, IL-6) in vivo and cell growth in vitro were almost the same between NU-1000 treatment and normal control groups. This study indicates NU-1000 is a promising vehicle for targeted peptide-based bioactive delivery to the small intestine.

Automated summary

NU-1000 immobilized with LDLQR successfully protected the peptide in stomach acid and pepsin environment, and ensured release under simulated intestinal conditions. LDLQR@NU-1000 could reduce blood sugar caused by maltose in mice without affecting inflammatory factors and cell growth. This study suggests NU-1000 is a promising vehicle for targeted peptide-based bioactive delivery to the small intestine.