Oral glucose- and pH-sensitive nanocarriers for simulating insulin release in vivo

Abstract

We design novel oral glucose sensitive nanocarriers for simulating insulin release using a modification of mesoporous silica nanoparticles (MSN) surfaces with a sensitive shell and conduct in vivo testing of these nanocarriers in diabetic rats. Here, MSN are coated with pH-sensitive dextran–maleic acid (Dex–Ma) and then grafted with glucose-sensitive 3-amidophenylboronic acid (APBA). These core–shell nanocarriers are confirmed by FT-IR, TEM, TGA, N₂ adsorption–desorption method and elemental analysis. The results indicate that the MSN core can efficiently increase the loading capacity of insulin. In vitro insulin release shows good glucose-trigged behavior, in addition the rate of insulin release can be easily adjusted by changing the shell thickness. The cell viability of the nanocarriers against calu-3 cells demonstrates excellent cytocompatibility, and the nanocarriers can be internalized into cells. According to the studies of diabetic rats in vivo, the oral insulin-loaded nanocarriers produce an obvious hypoglycemic effect compared with insulin directly given orally. Study of the ligated intestinal loops absorption indicates that the material can enhance the permeation of insulin across the epidermis of intestine and facilitate the uptake of insulin. Therefore, the simple and effective pH- and glucose-sensitive nanocarrier can be regarded as a potential self-regulated tool to simulate insulin release in vivo.