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  5. Local delivery of macromolecules to treat diseases associated with the colon
 
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Local delivery of macromolecules to treat diseases associated with the colon

Author(s)
Bak, A.  
Ashford, Marianne B.  
Brayden, David James  
Uri
http://hdl.handle.net/10197/10611
Date Issued
2018-11
Date Available
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.
Sponsorship
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
Subjects

Colonic drug discover...

Oral macromolecule de...

Large intestine

Inflammatory bowel di...

Colorectal cancer

Enteric infections

DOI
10.1016/j.addr.2018.10.009
Language
English
Status of Item
Peer reviewed
ISSN
0169-409X
This item is made available under a Creative Commons License
https://creativecommons.org/licenses/by-nc-nd/3.0/ie/
File(s)
No Thumbnail Available
Name

Bak et al RMS.docx

Size

912.61 KB

Format

Unknown

Checksum (MD5)

d1d9c6fca17c55412d0089f74bec7eb2

Owning collection
Veterinary Medicine Research Collection

Item descriptive metadata is released under a CC-0 (public domain) license: https://creativecommons.org/public-domain/cc0/.
All other content is subject to copyright.

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