An overview of site-specific delivery of orally administered proteins/peptides and modelling considerations

Abstract

Oral delivery of proteins and peptides poses one of the greatest challenges in controlled drug delivery due to degradation by proteolytic enzymes, poor membrane permeability and large molecular size. Therapeutic proteins/peptides are useful in correcting metabolic disorders (e.g., insulin in diabetes mellitus), as antineoplastic agents (e.g., cyclosporin A) and in hormone therapy (e.g., leutinizing hormone releasing hormone analogs in endometriosis and uterine fibroids). Thus, the importance of determining absorption efficiency of peptide and protein drugs is an important consideration. In oral peptide administration, the ideal delivery system is one that releases its contents only at the target region of the gastrointestinal tract (GIT) independent of patient variables while retaining the protein/peptide drug and their absorption promoters at the site of optimal absorption long enough to ultimately achieve maximum therapeutic benefit and safety. Various systems for achieving site-specific delivery of orally administered protein/peptide drugs have been developed in recent years including those based on pH changes, enzymatic activity of intestinal microflora, etc. This article discusses some of these systems including their relative merits and drawbacks. Some relevant mathematical models to resolve release patterns are also considered.