Lookup NU author(s): Dr Matthew Wilcox,
Dr Peter Chater,
Professor Jeffrey Pearson
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The effectiveness of delivering oral therapeutic peptides, proteins and nucleotides is often hindered by the protective mucus barrier that covers mucosal surfaces of the gastrointestinal (GI) tract. Encapsulation of active pharmaceutical ingredients (API) in nanocarriers is a potential strategy to protect the cargo but they still have to pass the mucus barrier. Decorating nanoparticles with proteolytic enzymes has been shown to increase the permeation through mucus. Here we investigate the effect of poly(acrylic acid) (PAA) nanoparticles decorated with bromelain (BRO), a proteolytic enzyme from pineapple stem, on the bulk rheology of mucus as well as non-decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Porcine intestinal mucus from the small intestine was incubated for 30 min in the presence of PLGA nanoparticles or polyacrylic nanoparticles decorated with bromelain (PAA-BRO). The effect of nanoparticles on the rheological properties, weight of gel, released glycoprotein content from mucus as well as the viscosity of liquid removed was assessed. Treatment with nanoparticles decreased mucus gel strength with PAA-BRO reducing it the most. PAA-BRO nanoparticles resulted in the release of increased glycoprotein from the gel network whereas mucus remained a gel and exhibited a similar breakdown stress to control mucus. Therefore it would be possible to use bromelain to increase the permeability of nanoparticles through mucus without destroying the gel and leaving the underlying mucosa unprotected. (C) 2015 Elsevier B.V. All rights reserved.
Author(s): Wilcox MD, Van Rooij LK, Chater PI, de Sousa IP, Pearson JP
Publication type: Article
Publication status: Published
Journal: European Journal of Pharmaceutics and Biopharmaceutics
Print publication date: 01/10/2015
Online publication date: 28/02/2015
Acceptance date: 07/03/2015
ISSN (print): 0939-6411
ISSN (electronic): 1873-3441
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