Investigation of peptide-based GI drug delivery vehicles using phage display technology

Abstract

Introduction: Oral administration of drugs is one of the most desirable routes for drug administration. However, low bioavailability of some therapeutic agents leads to application of non-oral routes which will be unpleasant for patients. Therefore, the development of drug delivery systems for the delivery of drugs with low absorption throughout the gasterointestinal (GI) barrier can significantly increase the oral bioavailability of such therapeutics. In this context, phage display technique can be used to identify peptides that specifically cross the intestinal barrier and hence used as specific vehicles. Objective: The aim of this study was to use phage display technique to identify peptides responsible for transmucosal transport of phage particles with the aim of developing vehicles for GI delivery of pharmaceuticals. Methods: In this study, in vivo phage display was applied in order to isolate sequences which may be responsible for transmucosal transport. A biopanning protocol was performed by applying a 12-mer random amino acid phage library to mice by gavage and then assessing their absorption via phage recovery from the blood. Following the recovery of phage particles from each round of biopanning, the sequences of displayed peptides were identified. The obtained sequences were analyzed using bioinformatics tools and software. Results: The analyses of peptide sequences revealed that GI translocation of phage particles did not depend on the presence of any particular peptide sequence and there is no significant consensus sequence among the identified peptides. Additionally, the random distribution of amino acids in different positions of peptides indicates their non-specific translocation through the intestinal mucosal barrier. Conclusion: According to the obtained results, the translocation of phage bearing 12 mer peptides across the intestinal mucosal barrier is non-specific and does not depend on specific transport pathways/transporters throughout the mucosal barrier.