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© 2015 Elsevier B.V.The intestinal mucus gel layer represents a stumbling block for drug adsorption. This study is aimed to formulate a nanoparticulate system able to overcome this barrier by cleaving locally the glycoprotein substructures of the mucus. Mucolytic enzymes such as papain (PAP) and bromelain (BRO) were covalently conjugated to poly(acrylic acid) (PAA). Nanoparticles (NPs) were then formulated via ionic gelation method and characterized by particle size, zeta potential, enzyme content and enzymatic activity. The NPs permeation quantified by rotating tube studies was correlated with changes in the mucus gel layer structure determined by pulsed-gradient-spin-echo NMR (PGSE-NMR), small-angle neutron scattering (SANS) and spin-echo SANS (SESANS). PAP and BRO functionalized NPs had an average size in the range of 250 and 285 nm and a zeta potential that ranged between -6 and -5 mV. The enzyme content was 242 μg enzyme/mg for PAP modified NPs and 253 μg enzyme/mg for BRO modified NPs. The maintained enzymatic activity was 43% for PAP decorated NPs and 76% for BRO decorated NPs. The rotating tube technique revealed a better performance of BRO decorated NPs compared to PAA decorated NPs, with a 4.8-fold higher concentration of NPs in the inner slice of mucus. Addition of 0.5 wt% of enzyme functionalized NPs to 5 wt% intestinal mucin led to c.a. 2-fold increase in the mobility of the mucin as measured by PGSE-NMR indicative of a significant break-up of the structure of the mucin. SANS and SESANS measurements further revealed a change in structure of the intestinal mucus induced by the incorporation of the functionalized NPs mostly occurring at a length scale longer than 0.5 μm. Accordingly, BRO decorated NPs show higher potential than PAP functionalized NPs as mucus permeating drug delivery systems.
Author(s): Pereira De Sousa I, Cattoz B, Wilcox MD, Griffiths PC, Dalgliesh R, Rogers S, Bernkop-Schnurch A
Publication type: Article
Publication status: Published
Journal: European Journal of Pharmaceutics and Biopharmaceutics
Year: 2015
Volume: 97
Issue: Part A
Pages: 257-264
Print publication date: 01/11/2015
Online publication date: 07/02/2015
Acceptance date: 12/01/2015
ISSN (print): 0939-6411
ISSN (electronic): 1873-3441
Publisher: Elsevier
URL: http://doi.org/10.1016/j.ejpb.2015.01.008
DOI: 10.1016/j.ejpb.2015.01.008
PubMed id: 25661320
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