Abstract
Systemic therapy upon oral delivery of biologies, such as peptide and protein drugs is limited due to their large molecular size, their low enzymatic stability and their inability to cross the intestinal epithelium. Ways to overcome the epithelial barrier include the use of peptide-based excipients such as the cell penetrating peptides (CPPs) and the tight junction modulating peptides (TJMPs), which are able to translocate across the cellular membranes in a non-disruptive way or reversibly modulate the integrity of intercellular tight junctions (TJs), respectively. However, because of the harsh environment throughout the gastrointestinal (GI) tract, chemical stability is an inherent challenge when employing amino acid-based excipients for oral delivery, and multiple approaches have been investigated to improve this. The exact mechanisms of transepithelial translocation are discussed, and it is believed that CPP-mediated translocation involves transcytosis and/or direct translocation through the epithelial cells; whereas TJMP-mediated translocation is dependent on interaction with transmembrane or peripheral TJ proteins. This review focuses on the CPPs and the TJMPs currently employed as excipients for oral delivery of peptide and protein drugs highlighting recent studies and the most promising compounds from these classes of peptide excipients.
| Original language | English |
|---|---|
| Journal | Journal of Drug Delivery Science and Technology |
| Volume | 23 |
| Issue number | 4 |
| Pages (from-to) | 365-373 |
| Number of pages | 9 |
| ISSN | 1773-2247 |
| Publication status | Published - 2013 |
| Externally published | Yes |