Skip navigation

Nanoparticle diffusion within intestinal mucus: Three-dimensional response analysis dissecting the impact of particle surface charge, size and heterogeneity across polyelectrolyte, pegylated and viral particles

Nanoparticle diffusion within intestinal mucus: Three-dimensional response analysis dissecting the impact of particle surface charge, size and heterogeneity across polyelectrolyte, pegylated and viral particles

Abdulkarim, Muthanna, Agulló, Nuria, Cattoz, Beatrice, Griffiths, Peter ORCID: 0000-0002-6686-1271, Bernkop-Schnürch, Andreas, Borros, Salvador Gómez and Gumbleton, Mark (2015) Nanoparticle diffusion within intestinal mucus: Three-dimensional response analysis dissecting the impact of particle surface charge, size and heterogeneity across polyelectrolyte, pegylated and viral particles. European Journal of Pharmaceutics and Biopharmaceutics, 97 (A). pp. 230-238. ISSN 0939-6411 (doi:10.1016/j.ejpb.2015.01.023)

[img] PDF (Publisher PDF)
13153_Cattoz_Nanoparticle diffusion (pub PDF) 2015.pdf - Published Version
Restricted to Repository staff only

Download (836kB)

Abstract

Multiple particle tracking (MPT) methodology was used to dissect the impact of nanoparticle surface charge and size upon particle diffusion through freshly harvested porcine jejunum mucus. The mucus was characterised rheologically and by atomic force microscopy. To vary nanoparticle surface charge we used a series of self-assembly polyelectrolyte particles composed of varying ratios of the negatively charged polyacrylic acid polymer and the positively charged chitosan polymer. This series included a neutral or near-neutral particle to correspond to highly charged but near-neutral viral particles that appear to effectively permeate mucus. In order to negate the confounding issue of self-aggregation of such neutral synthetic particles a sonication step effectively reduced particle size (to less than 340 nm) for a sufficient period to conduct the tracking experiments. Across the polyelectrolyte particles a broad and meaningful relationship was observed between particle diffusion in mucus (×1000 difference between slowest and fastest particle types), particle size (104–373 nm) and particle surface charge (−29 mV to +19.5 mV), where the beneficial characteristic promoting diffusion was a neutral or near-neutral charge. The diffusion of the neutral polyelectrolyte particle (0.02887 cm S−1 × 10−9) compared favourably with that of a highly diffusive PEGylated-PLGA particle (0.03182 cm2 S−1 × 10−9), despite the size of the latter (54 nm diameter) accommodating a reduced steric hindrance with the mucin network. Heterogeneity of particle diffusion within a given particle type revealed the most diffusive 10% sub-population for the neutral polyelectrolyte formulation (5.809 cm2 S−1 × 10−9) to be faster than that of the most diffusive 10% sub-populations obtained either for the PEGylated-PLGA particle (4.061 cm2 S−1 × 10−9) or for a capsid adenovirus particle (1.922 cm2 S−1 × 10−9). While this study has used a simple self-assembly polyelectrolyte system it has substantiated the pursuance of other polymer synthesis approaches (such as living free-radical polymerisation) to deliver stable, size-controlled nanoparticles possessing a uniform high density charge distribution and yielding a net neutral surface potential. Such particles will provide an additional strategy to that of PEGylated systems where the interactions of mucosally delivered nanoparticles with the mucus barrier are to be minimised.

Item Type: Article
Uncontrolled Keywords: mucus, polyelectrolyte, nanoparticles, multiple particle tracking, virus, diffusion
Subjects: R Medicine > RS Pharmacy and materia medica
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Department of Pharmaceutical, Chemical & Environmental Sciences
Last Modified: 17 Oct 2016 09:13
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
URI: http://gala.gre.ac.uk/id/eprint/13153

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics