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Liposomes targeted to deliver antisecretory agents to jejunal mucosa Open Access
- Author or creator
Uwiera, Richard R. E.
Romancyia, D. A.
Wong, Jonathan P.
Forsyth, George W.
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The B subunit of cholera toxin has been covalently attached to the surface of Uposomes made from a mixture of phosphatidylethanolamine, phosphati- dylcholine and cholesterol. Adenylate cydase inhibitors and chloride conduc- tance inhibitors were encapsulated within the liposomes. These \"targeted\" liposomes were used to study the com- bined effects of this novel delivery sys- tem, and a lmited number of possible antisecretory agents, on net fluid flux into the pig jejunum. A state of net secretory fluid flux was induced in isolated jejunal loops in weanling pigs by adding theophyfline or cholera toxin to the lumen of the isolated loops. There was no reduction in net fluid secretion when liposome suspensions without encapsulated secretory inhibitors were added to fluid in the lumen of loops treated with theophyiline. There was also no reduc- tion in net fluid secretion when mico- nazole, a-phenylcinnamate or 5 nitro- 2-(3-phenethylamino)benzoate were encapsulated within targeted liposomes added to isolated jejunal loops. The net fluid flux induced by exposure of jejunal loops to theophylline was sig- nificantly reduced by adding targeted liposomes containing 2' -deoxy-3' - AMP. The reduction involved a rever- sal of net secretory fluid flux to an absorptive value. The net fluid secretory response to treatment of loops with cholera toxin was also inhibited by treating loops with targeted liposomes containing 2' -deoxy-3 -AMP. However, the reversal of secretion was less complete for secretion induced by cholera toxin than for secretion induced by theo- phylline. The reduced antisecretory efficacy versus cholera toxin was not improved by encapsulating higher con- centrations of 2 '-deoxy-3' -AMP. A larger dose of the inhibitor delivered with increased numbers of liposomes caused a significant reduction in net fluid secretion. Occupancy of mucosal receptors by native cholera toxin may be a factor limiting access of liposomes with surface B subunit, and may reduce the utility of the B subunit of cholera toxin as a targeting agent for delivering antisecretory agents to the intestinal mucosa.
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- © 1992 The Canadian Veterinary Medical Association. This version of this article is open access and can be downloaded and shared. The original author(s) and source must be cited.
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Uwiera, R. R. E., Romancyia, D. A., Wong, J. P., & Forsyth, G. W. (1992). Liposomes targeted to deliver antisecretory agents to jejunal mucosa. Canadian Journal of Veterinary Research, 56(3), 249-255. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1263547/
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