A Delivery System for Oral Administration of Proteins/Peptides Through Bile Acid Transport Channels

Abstract

Proteins and peptides are poorly absorbed via oral administration because of the gastrointestinal tract environment and lysosomal digestion after apical endocytosis. A delivery system, consisting of a deoxycholic acid–conjugated nanometer-sized carrier, may enhance the absorption of proteins in the intestine via the bile acid pathway. Deoxycholic acid is first conjugated to chitosan. Liposomes are then prepared and loaded with the model drug insulin. Finally, the conjugates are bound to the liposome surface to form deoxycholic acid and chitosan conjugate–modified liposomes (DC-LIPs). This study demonstrates that DC-LIPs can promote the intestinal absorption of insulin via the apical sodium-dependent bile acid transporter, based on observing fluorescently stained tissue slices of the rat small intestine and a Caco-2 cell uptake experiment. Images of intestinal slices revealed that excellent absorption of DC-LIPs is achieved via apical sodium-dependent bile acid transporter, and a flow cytometry experiment proved that DC-LIPs are a highly efficient delivery carrier. Caco-2 cells were also used to study the lysosome escape ability of DC-LIPs. We learned from confocal microscopy photographs that DC-LIPs can protect their contents from being destroyed by the lysosome. Finally, according to pharmacokinetic analyses, insulin-loaded DC-LIPs show a significant hypoglycemic effect with an oral bioavailability of 16.1% in rats with type I diabetes.