title: The effect of nanoparticle permeation on the bulk rheological properties of mucus from the small intestine.
abstract: 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 30min 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.
authors.affiliation: The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Electronic address: matthew.wilcox@ncl.ac.uk.
authors.forename: M D
authors.initials: MD
authors.lastname: Wilcox
authors.affiliation: The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: L K
authors.initials: LK
authors.lastname: Van Rooij
authors.affiliation: The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: P I
authors.initials: PI
authors.lastname: Chater
authors.affiliation: Institute of Pharmacy, Department of Pharmaceutical Technology, University of Innsbruck, Innrain 80-82/IV, 6020 Innsbruck, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Pereira de Sousa
authors.affiliation: The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Pearson
mesh_terms: D000003:Abattoirs; D000180:Acrylic Resins / Q000737:chemistry*; D031230:Ananas / Q000201:enzymology; D000818:Animals; D001963:Bromelains / Q000378:metabolism*; D004337:Drug Carriers; D004800:Enzymes, Immobilized / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D019344:Lactic Acid / Q000737:chemistry; D009093:Mucus / Q000737:chemistry / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D010539:Permeability; D010940:Plant Proteins / Q000378:metabolism; D018547:Plant Stems / Q000201:enzymology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012212:Rheology; D013499:Surface Properties; D034421:Sus scrofa; D014783:Viscosity
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D004800:Enzymes, Immobilized; D006023:Glycoproteins; D010940:Plant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C006903:carbopol 940; D001963:Bromelains
keywords: Bromelain; Glycoprotein; Nanoparticle; Rheology; Small intestinal mucus