Macromolecules comprise a growing group of new pharmaceutical products with the potential to treat diseases that heretofore have had no effective therapeutic options.
To date, the therapeutic application of these drugs has been limited because they are effective only when administered parenterally.
Since the discovery of insulin and heparin in the early 1900s, there has been keen interest in solving the problem of orally delivering macromolecules safely and effectively. Various approaches have been investigated including altering the intestinal membrane, targeting intestinal transport mechanisms, chemically altering the drug and carrier-assisted transport mechanisms.
To date, the most promising approach has been the carrier-assisted approach, which has advanced seven different macromolecules or highly charged small molecules human proof-of-concept testing.
The rapid integration of new technologies by the pharmaceutical industry has resulted in numerous breakthroughs in the discovery, development and manufacturing of pharmaceutical products. In particular, the commercial-scale production of high-purity recombinant proteins has resulted in important additions to treatment options for many large therapeutic areas. In addition to proteins, other macromolecules, such as the animal-derived mucopolysacharide heparins, have also seen dramatic growth as injectable pharmaceutical products. To date, macromolecules have been limited as therapeutics by the fact that they cannot be orally delivered. This article will address the current status and future possibilities of oral macromolecular drug delivery.
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The extent to which a drug becomes available in the bloodstream, or at the target tissue, after administration.
The extent of insolubility in water or resistance to hydration of a molecule or chemical entity.
The extent of solubility in water or the ability to be hydrated of a molecule or chemical entity.
The process by which polarized cells transport certain molecules by engulfing them into vesicles that are released at the opposite side of the cells.
Epithelial cells that form the gastrointestinal wall.
- TIGHT JUNCTION
An intercellular junction that seals together adjacent epithelial cells, preventing the passage of substances through the spaces in between cells.
- FUNCTIONAL GROUP
A chemical group with specific properties attached to a molecule.
The way in which drugs are absorbed, distributed, localized in tissues, metabolized and excreted over a period of time.
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Goldberg, M., Gomez-Orellana, I. Challenges for the oral delivery of macromolecules. Nat Rev Drug Discov 2, 289–295 (2003). https://doi.org/10.1038/nrd1067
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