Local delivery of macromolecules to treat diseases associated with the colon

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Title: Local delivery of macromolecules to treat diseases associated with the colon
Authors: Bak, A.Ashford, Marianne B.Brayden, David J.
Permanent link: http://hdl.handle.net/10197/10611
Date: Nov-2018
Online since: 2019-05-22T11:34:52Z
Abstract: Current treatments for intestinal diseases including inflammatory bowel diseases, irritable bowel syndrome, and colonic bacterial infections are typically small molecule oral dosage forms designed for systemic delivery. The intestinal permeability hurdle to achieve systemic delivery from oral formulations of macromolecules is challenging, but this drawback can be advantageous if an intestinal region is associated with the disease. There are some promising formulation approaches to release peptides, proteins, antibodies, antisense oligonucleotides, RNA, and probiotics in the colon to enable local delivery and efficacy. We briefly review colonic physiology in relation to the main colon-associated diseases (inflammatory bowel disease, irritable bowel syndrome, infection, and colorectal cancer), along with the impact of colon physiology on dosage form design of macromolecules. We then assess formulation strategies designed to achieve colonic delivery of small molecules and concluded that they can also be applied some extent to macromolecules. We describe examples of formulation strategies in preclinical research aimed at colonic delivery of macromolecules to achieve high local concentration in the lumen, epithelial-, or sub-epithelial tissue, depending on the target, but with the benefit of reduced systemic exposure and toxicity. Finally, the industrial challenges in developing macromolecule formulations for colon-associated diseases are presented, along with a framework for selecting appropriate delivery technologies.
Funding Details: European Commission - European Regional Development Fund
Science Foundation Ireland
Type of material: Journal Article
Publisher: Elsevier
Journal: Advanced Drug Delivery Reviews
Volume: 136-137
Start page: 2
End page: 27
Copyright (published version): 2018 Crown
Keywords: Colonic drug discoveryOral macromolecule deliveryLarge intestineInflammatory bowel diseaseColorectal cancerEnteric infections
DOI: 10.1016/j.addr.2018.10.009
Language: en
Status of Item: Peer reviewed
Appears in Collections:Veterinary Medicine Research Collection

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