A permeable on-chip microvasculature for assessing the transport of macromolecules and polymeric nanoconstructs.
Microfluidic
Nanoparticles
Permeability
Vascular adhesion
Journal
Journal of colloid and interface science
ISSN: 1095-7103
Titre abrégé: J Colloid Interface Sci
Pays: United States
ID NLM: 0043125
Informations de publication
Date de publication:
15 Jul 2021
15 Jul 2021
Historique:
received:
30
12
2020
revised:
23
02
2021
accepted:
09
03
2021
pubmed:
29
3
2021
medline:
22
6
2021
entrez:
28
3
2021
Statut:
ppublish
Résumé
The selective permeation of molecules and nanomedicines across the diseased vasculature dictates the success of a therapeutic intervention. Yet, in vitro assays cannot recapitulate relevant differences between the physiological and pathological microvasculature. Here, a double-channel microfluidic device was engineered to comprise vascular and extravascular compartments connected through a micropillar membrane with tunable permeability. The vascular compartment was coated by endothelial cells to achieve permeability values ranging from ~0.1 μm/sec, following a cyclic adenosine monophosphate (cAMP) pre-treatment (25 μg/mL), up to ~2 μm/sec, upon exposure to Mannitol, Lexiscan or in the absence of cells. Fluorescent microscopy was used to monitor the vascular behavior of 250 kDa Dextran molecules, 200 nm polystyrene nanoparticles (PB), and 1,000 × 400 nm discoidal polymeric nanoconstructs (DPN), under different permeability and flow conditions. In the proposed on-chip microvasculature, it was confirmed that permeation enhancers could favor the perivascular accumulation of ~200 nm, in a dose and time dependent fashion, while have no effect on larger particles. Moreover, the microfluidic device was used to interrogate the role of particle deformability in vascular dynamics. In the presence of a continuous endothelium, soft DPN attached to the vasculature more avidly at sub-physiological flows (100 μm/sec) than rigid DPN, whose deposition was larger at higher flow rates (1 mm/sec). The proposed double-channel microfluidic device can be efficiently used to systematically analyze the vascular behavior of drug delivery systems to enhance their tissue specific accumulation.
Identifiants
pubmed: 33774397
pii: S0021-9797(21)00346-5
doi: 10.1016/j.jcis.2021.03.053
pii:
doi:
Substances chimiques
Polymers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
409-423Subventions
Organisme : European Research Council
ID : 616695
Pays : International
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.