The rapid expansion of applied biotechnology research in current pharmaceutical drug discovery has resulted in the development of increasing numbers of novel macromolecular therapeutics. Oral bioavailability of these compounds is usually poor due to a combination of incompatible physicochemical properties, resulting in low cellular penetration, and high susceptibility to metabolic enzymes present within the gastrointestinal tract. For chronic drug therapy, however, the oral pathway is generally considered to be the most convenient route of administration. Thus far, limited success has been observed in oral macromolecular delivery by either concomitant administration of penetration enhances or the use of prodrug strategies involving carrier-mediated transport systems. An alternative approach may be targeting to receptor-mediated endocytosis (RME) systems. It is the aim of this mini-review to present a concise overview of the latest developments in RME research and RME systems that are either currently targeted for the oral delivery of macromolecules or may appear to become potential targets for future oral drug delivery strategies.
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