Chemically modified peptides and proteins - critical considerations for oral delivery

abstract

Numerous approaches have been explored to date in the pursuit of delivering peptides or proteins via the oral route. One such example is chemical modification, whereby the native structure of a peptide or protein is tailored to provide a more efficient uptake across the epithelial barrier of the gastrointestinal tract via incorporation of a chemical motif or moiety. In this regard, a diverse array of concepts have been reported, ranging from the exploitation of endogenous transport mechanisms to incorporation of physicochemical modifications in the molecule, which promote more favorable interactions with the absorptive membrane at the cell surface. This review provides an overview of the modification technologies described in the literature and offers insights into some pragmatic considerations pertaining to their translation into clinically viable concepts.

KEYWORDS:

• absorption
• bioconjugate
• chemical modification
• cell penetrating peptide
• ligand-attachment
• lipidisation
• oral delivery
• peptide
• protein

Disclosure of potential conflicts of interest

The authors declare the following competing financial interest(s): S.T.B., F.H. and U.L.R. are employees and shareholders of Novo Nordisk A/S. The views and opinions expressed are those of the authors and do not necessarily reflect that of Novo Nordisk A/S.