Design of Auto-Adaptive Drug Delivery System for Effective Delivery of Peptide Drugs to Overcoming Mucus and Epithelial Barriers

Oral administration of peptide represents a promising delivery route, however, it is hindered by the harsh gastrointestinal environment, leading to low in vivo absorption. In this study, auto-adaptive protein corona-AT 1002-cationic liposomes (Pc-AT-CLs) are constructed with the characteristic of hydrophilic and electrically neutral surface properties for the encapsulation of liraglutide. BSA protein corona is used to coat AT-CLs reducing the adherence of mucus, and may fall off after penetrating the mucus layer. Transmucus transport experiment demonstrated that the mucus penetration amount of Pc-AT-CLs are 1.45 times that of AT-CLs. After penetrating the mucus layer, AT-CLs complete transmembrane transport by the dual action of AT and cationic surface properties. Transmembrane transport experiment demonstrated that the apparent permeability coefficient (P_app) of AT-CLs is 2.03 times that of CLs. In vivo tests demonstrated that Pc-AT-CLs exhibited a significant hypoglycemic effect and enhanced the relative bioavailability comparing to free liraglutide. Pc-AT-CLs protect liraglutide from degradation, facilitate its absorption, and ultimately improve its oral bioavailability.

In this study, AT-CLs (AT-1002 peptide attached to cationic liposomes) and coated with BSA (bovine serum albumin) together form Pc-AT-CLs. The purpose of simultaneously improved mucus permeating ability and transepithelial absorption. When the carrier penetrates the mucus, the BSA protein corona coating may fall off. Then, AT-CLs carriers possessing cationic and hydrophobic surfaces, which will facilitate uptake of intracellular and paracellular.

Fig: The schematic diagram of Pc-AT-CLs administration and the transport process through the mucus layer and epithelial barrier.