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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

Albaldawi, Muthanna, Agulló, Nuria, Cattoz, Beatrice, Griffith, Peter, 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 (Part A) , pp. 230-238. 10.1016/j.ejpb.2015.01.023

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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 (x1000 difference between slowest and fastest particle types), particle size (104 nm to 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 cm2.S-1 x10-9) compared favourably with that of a highly diffusive PEGylated-PLGA particle (0.03182 cm2.S-1 x10-9), 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 x10-9) be faster than that of the most diffusive 10% sub-populations obtained for either the PEGylated-PLGA particle (4.061 cm2.S-1 x10-9) or for a capsid adenovirus particle (1.922 cm2.S-1 x10-9). 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 yielding net neutral surface potential. Such particles that 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
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Mucus; Polyelectrolyte; Nanoparticles; Multiple particle tracking; Virus; Diffusion
Additional Information: Research supported by EC FP7 large-scale integrating project grant: Project number 280761 to the ALEXANDER consortium project 'Mucus Permeating Nanoparticulate Drug Delivery Systems' in the topic area NMP-2011-1.2-2 'New targeted therapy using nanotechnology for transport of macromolecules across biological barriers”
Publisher: Elsevier
ISSN: 0939-6411
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 25 January 2015
Last Modified: 24 Nov 2020 17:19

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