Mucus penetrating properties of soft, distensible lipid nanocapsules

TY - JOUR

T1 - Mucus penetrating properties of soft, distensible lipid nanocapsules

AU - Chen, Hanpeng

AU - Mansfield, Edward D.H.

AU - Woods, Arcadia

AU - Khutoryanskiy, Vitaliy V.

AU - Forbes, Ben

AU - Jones, Stuart A.

PY - 2019/6

Y1 - 2019/6

N2 - 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 × 10 −10 cm 2 s −1 ) compared to equivalent-sized negatively charged polystyrene particles (9.87 ± 0.61 × 10 −10 cm 2 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 particle 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 × 10 −8 cm 2 s −1 , p < 0.05) compared to the non-distended materials (4.94 ± 0.04 × 10 −8 cm 2 s −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 tortuous path through the barrier, i.e., they experienced less steric hinderance, compared to the non-distended LNC.

AB - 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 × 10 −10 cm 2 s −1 ) compared to equivalent-sized negatively charged polystyrene particles (9.87 ± 0.61 × 10 −10 cm 2 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 particle 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 × 10 −8 cm 2 s −1 , p < 0.05) compared to the non-distended materials (4.94 ± 0.04 × 10 −8 cm 2 s −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 tortuous path through the barrier, i.e., they experienced less steric hinderance, compared to the non-distended LNC.

KW - Cystic fibrosis

KW - Diffusion

KW - Lipid

KW - Mucoadhesion

KW - Mucus

KW - Nanomaterial

KW - Nanoparticle

KW - Penetration

KW - Polystyrene

KW - Size

KW - Surface charge

KW - Zeta potential

UR - http://www.scopus.com/inward/record.url?scp=85062830901&partnerID=8YFLogxK

U2 - 10.1016/j.ejpb.2019.02.020

DO - 10.1016/j.ejpb.2019.02.020

M3 - Article

AN - SCOPUS:85062830901

SN - 0939-6411

VL - 139

SP - 76

EP - 84

JO - EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

JF - EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

ER -