15 March 2013
SCI's Biotechnology Group in conjunction with the University of Westminster
University of Westminster, London
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Non-parental delivery of biopharmaceuticals is highly attractive not only for its improved convenience and potential to localise the delivery to some agents to the lung or gut where they are administered. Oral delivery has been suggested to have additional advantages relative to subcutaneous (SC) injection: a greater safety-to-efficacy ratio for molecules with targets in the liver and the potential for reduced immunogenicity.
Additional potential benefits for oral bio-therapeutic delivery involve general health and safety as well as environmental concerns. Studies have examined a strategy of emulating certain bacterial toxins to identify a potential approach to achieve the goal of non-parenteral delivery of biopharmaceuticals. Specifically, in examination of mechanisms(s) used by exotoxin A from Pseudomonas aerugionsa (PE) to efficiently transport its toxic cargo through polarized epithelial cell without intoxicating them. Once across an epithelial barrier, PE targets cells enriched in surface-expressed CD91, a large scavenger (low density lipoprotein-like receptor) protein.
The modular nature o PE allows it to be easily manipulated be genetic engineering: a non-toxic form of PE can be used to deliver antigenic structures to professional antigen presenting cells following mucosal application and use of just the transcelluar transport elements can allow for the systematic delivery of protein therapeutics. Thus, the remarkable nature of microbial toxins rapidly enter and transport across polarized epithelial cells can be exploited for a variety of applications that might provide pharmaceutical benefit.
University of Westminster
University of Westminster, School of Life Sciences, 115 New Cavendish Street London W1W 6UW
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Professor Randal Mrsny
Deparment of Pharamacy and Pharmacology, University of Bath