STUDJES ON ORAL DELIVERY OF ('ERTAIN PEPTIDE DERIVATIVES

Abstract

Rapid developments in biotechnology have posed new challenges for pharmaceutical researchers to develop peptide and protein drugs. Many efforts are directed towards achieving non­ parenteral delivery routes of these agents. Although each non­ parenteral route has its own advantages and disadvantages, the oral route is by every means the preferred route of drug administration especially for therapeutics used chronically.

It is common knowledge that peptide and protein drugs are easily hydrolyzed and digested in the gastrointestinal tract. In addition, they have poor membrane permeability due to their hydrophilicity and large molecular size.

Among the many strategies used in attempts to improve the oral bioavailability of peptide and protein drugs, is using site-specific delivery to the colon to bypass the harsh gastrointestinal environment and using absorption enhancers to improve their poor intestinal absorption.

In this study, the effect of a novel group of absorption enhancers (the nitric oxide donors) was explored using two peptide drugs, insulin and calcitonin. Their effect was first compared to the effect of conventional enhancers from different classes using the model drug, 5-(6)-carboxyfluorescein. Following that, the combined effect of using site-specific delivery through the. formulation approach together with using additives was investigated.