Permeation characteristics of oligoarginine through intestinal epithelium and its usefulness for intestinal peptide drug delivery.

Cell-penetrating peptides such as HIV-1 Tat and oligoarginine are attractive tools for the intracellular delivery of therapeutic macromolecules. Although we have found that oligoarginine enhances the intestinal absorption of therapeutic peptides, especially insulin, the mechanism underlying the ability of oligoarginine to increase intestinal drug absorption is unclear. In addition, there is no information about the permeation characteristics of these functional peptides through the biological intestinal membrane.

A novel approach using functional peptides for efficient intestinal absorption of insulin.

The aim of this study was to evaluate whether oligoarginine, a cell-penetrating peptide (CPP), can improve intestinal absorption of insulin in rats. Peptides composed of six (R(6)), eight (R(8)) and 10 (R(10)) residues of arginine were used as the CPP. No insulin absorption was observed following administration of insulin solution alone; however, insulin absorption increased dramatically after coadministration of the D-form of R(6) (D-R(6)) and the L-form of R(6) (L-R(6)) in a dose-dependent manner.

Novel mucosal insulin delivery systems based on fusogenic liposomes.

Purpose: Fusogenic liposomes (FLs) are unique delivery vehicles capable of introducing their contents directly into the cytoplasm with the aid of envelope glycoproteins of Sendai virus (SeV). The objective of this study was to evaluate the potential of FL to improve the mucosal absorption of insulin from rat intestinal membranes.

Method: The FLs containing insulin were prepared by fusing insulin-loaded liposomes with inactivated SeV particles and were administered directly into the ileal, the colonic, and the rectal loops (10 IU/kg).