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PEGylated silicon nanowire coated silica microparticles for drug delivery across intestinal epithelium.

Abstract：

:Composite particles made by growing nanoscopic silicon wires from the surface of monodispersed, microsized silica beads were tested in this study for their ability to affect the integrity and permeability of an epithelial cell layer. Polyethylene glycol (PEG) is known to sterically stabilize particles and prevent protein binding; as such, it is a routine way to impart in vivo longevity to drug carriers. The effect of the silica beads, both with and without silicon nanowires and PEG, on the disruption of the tight junctions in Caco-2 cells was evaluated by means of: (a) analysis of the localization of zonula occludens-1 (ZO-1), claudin-1 and f-actin; (b) measurements of trans-epithelial electrical resistance (TEER); (c) real-time quantitative RT-PCR analysis of the expression of PKC-α and PKC-z, which regulate the fluidity of cell membranes, and RhoA and Rac1, which are mainly involved in mechanotransduction processes; and (d) drug permeability experiments with fluorescein-sodium. The results have shown that Si-nanowire-coated silica microparticles added to Caco-2 cells in culture lead to alterations in tight junction permeability and the localization of ZO-1 and f-actin, as well as to decreased width of ZO-1 and claudin-1 at the tight junction and increased expression of PKC transcripts. Si-nanowire-coated silica microparticles increased the permeability of Caco-2 cell monolayers to fluorescein-sodium in proportion to their amount. Effects indicative of loosening the Caco-2 cell monolayers and increasing their permeability were less pronounced for PEGylated particles, owing to their greater supposed inertness in comparison with the non-functionalized beads and nanowires. The analyzed Si-nanowire-coated silica microparticles have thus been shown to affect membrane barrier integrity in vitro, suggesting the possibility of using nanostructured microparticles to enhance drug permeability through the intestinal epithelium in vivo.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Uskoković V,Lee PP,Walsh LA,Fischer KE,Desai TA

doi

10.1016/j.biomaterials.2011.11.010

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

1663-72

issue

5

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(11)01348-2

journal_volume

33

pub_type

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