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Mucus penetrating properties of soft, distensible lipid nanocapsules

Chen, H., Mansfield, E. D. H., Woods, A., Khutoryanskiy, V. V., Forbes, B. and Jones, S. A. (2019) Mucus penetrating properties of soft, distensible lipid nanocapsules. European Journal of Pharmaceutics and Biopharmaceutics. ISSN 0939-6411 (In Press)

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To link to this item DOI: 10.1016/j.ejpb.2019.02.020

Abstract/Summary

Designing nanomaterials to release their drug pay-load upon exposure to an exogenous trigger can help to direct drug delivery, but how the triggered release, which often modifies the nanomaterial properties, influences the biological fate of these systems is currently unknown. The aim of this study was to investigate how the triggered drug release from PEG coated, soft, 50 nm distensible lipid nanocapsules (LNC) influenced their diffusion across a mucus barrier. The translocation speed of the non-triggered LNC across a 35 µm thick purified gastric mucin (PGM) barrier was 3 times faster (30.08 ± 2.49 x 10-10 cm2 s-1) compared to equivalent-sized negatively charged polystyrene particles (9.87 ± 0.61 x 10-10 cm2 s-1, p < 0.05). In cystic fibrosis mucus (CFM), harvested from patient primary cells, the non-triggered LNC translocation speed was similar to the PGM, but the polystyrene particles diffusion was so slow it could not be measured. The trigger induced LNC distension process had no effect on the particle diffusion rate in both PGM and CFM (p > 0.05) in a static mucus barrier, but when shear was applied to the barrier the distended LNCs diffused more slowly (3.97 ± 1.38 x 10-8 cm2s-1, p < 0.05) compared to the non-distended materials (4.94 ± 0.04 x 10-8 cm2s-1). This data suggested the rapid mucus penetration of the distended LNCs, despite their increased size, was a consequence of their capacity to take a less tortious path through the barrier, i.e., they experienced less steric hinderance, compared to the non-distended LNC.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
ID Code:82562
Publisher:Elsevier

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