Drug permeation across intestinal epithelial cells using porous silicon nanoparticles

Luis M. Bimbo, Ermei Mäkilä, Timo Laaksonen, Vesa-Pekka Lehto, Jarno Salonen, Jouni Hirvonen, Hélder A. Santos

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Mesoporous silicon particles hold great potential in improving the solubility of otherwise poorly soluble drugs. To effectively translate this feature into the clinic, especially via oral or parenteral administration, a thorough understanding of the interactions of the micro- and nanosized material with the physiological environment during the delivery process is required. In the present study, the behaviour of thermally oxidized porous silicon particles of different sizes interacting with Caco-2 cells (both non-differentiated and polarized monolayers) was investigated in order to establish their fate in a model of intestinal epithelial cell barrier. Particle interactions and TNF-α were measured in RAW 264.7 macrophages, while cell viabilities, reactive oxygen species and nitric oxide levels, together with transmission electron microscope images of the polarized monolayers, were assessed with both the Caco-2 cells and RAW 264.7 macrophages. The results showed a concentration and size dependent influence on cell viability and ROS-, NO- and TNF-α levels. There was no evidence of the porous nanoparticles crossing the Caco-2 cell monolayers, yet increased permeation of the loaded poorly soluble drug, griseofulvin, was shown.

Original languageEnglish
Pages (from-to)2625-2633
Number of pages9
JournalBiomaterials
Volume32
Issue number10
Early online date30 Dec 2010
DOIs
Publication statusPublished - 30 Apr 2011
Externally publishedYes

Fingerprint

Caco-2 Cells
Porous silicon
Silicon
Permeation
Nanoparticles
Monolayers
Macrophages
Epithelial Cells
Cell Survival
Cells
Pharmaceutical Preparations
Griseofulvin
Particle interactions
Nitric oxide
Particle Size
Solubility
Reactive Oxygen Species
Nitric Oxide
Electron microscopes
Electrons

Keywords

  • animals
  • Caco-2 cells
  • cell death
  • cell membrane permeability
  • cell survival
  • epithelial cells
  • griseofulvin
  • humans
  • inflammation
  • intestines
  • intracellular space
  • macrophages
  • mice
  • nanoparticles
  • nitric oxide
  • oxidation-reduction
  • porosity
  • reactive oxygen species
  • silicon
  • solubility
  • temperature
  • tumor necrosis factor-alpha

Cite this

Bimbo, L. M., Mäkilä, E., Laaksonen, T., Lehto, V-P., Salonen, J., Hirvonen, J., & Santos, H. A. (2011). Drug permeation across intestinal epithelial cells using porous silicon nanoparticles. Biomaterials, 32(10), 2625-2633. https://doi.org/10.1016/j.biomaterials.2010.12.011
Bimbo, Luis M. ; Mäkilä, Ermei ; Laaksonen, Timo ; Lehto, Vesa-Pekka ; Salonen, Jarno ; Hirvonen, Jouni ; Santos, Hélder A. / Drug permeation across intestinal epithelial cells using porous silicon nanoparticles. In: Biomaterials. 2011 ; Vol. 32, No. 10. pp. 2625-2633.
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Bimbo, LM, Mäkilä, E, Laaksonen, T, Lehto, V-P, Salonen, J, Hirvonen, J & Santos, HA 2011, 'Drug permeation across intestinal epithelial cells using porous silicon nanoparticles', Biomaterials, vol. 32, no. 10, pp. 2625-2633. https://doi.org/10.1016/j.biomaterials.2010.12.011

Drug permeation across intestinal epithelial cells using porous silicon nanoparticles. / Bimbo, Luis M.; Mäkilä, Ermei; Laaksonen, Timo; Lehto, Vesa-Pekka; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A.

In: Biomaterials, Vol. 32, No. 10, 30.04.2011, p. 2625-2633.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Drug permeation across intestinal epithelial cells using porous silicon nanoparticles

AU - Bimbo, Luis M.

AU - Mäkilä, Ermei

AU - Laaksonen, Timo

AU - Lehto, Vesa-Pekka

AU - Salonen, Jarno

AU - Hirvonen, Jouni

AU - Santos, Hélder A.

N1 - Copyright © 2010 Elsevier Ltd. All rights reserved.

PY - 2011/4/30

Y1 - 2011/4/30

N2 - Mesoporous silicon particles hold great potential in improving the solubility of otherwise poorly soluble drugs. To effectively translate this feature into the clinic, especially via oral or parenteral administration, a thorough understanding of the interactions of the micro- and nanosized material with the physiological environment during the delivery process is required. In the present study, the behaviour of thermally oxidized porous silicon particles of different sizes interacting with Caco-2 cells (both non-differentiated and polarized monolayers) was investigated in order to establish their fate in a model of intestinal epithelial cell barrier. Particle interactions and TNF-α were measured in RAW 264.7 macrophages, while cell viabilities, reactive oxygen species and nitric oxide levels, together with transmission electron microscope images of the polarized monolayers, were assessed with both the Caco-2 cells and RAW 264.7 macrophages. The results showed a concentration and size dependent influence on cell viability and ROS-, NO- and TNF-α levels. There was no evidence of the porous nanoparticles crossing the Caco-2 cell monolayers, yet increased permeation of the loaded poorly soluble drug, griseofulvin, was shown.

AB - Mesoporous silicon particles hold great potential in improving the solubility of otherwise poorly soluble drugs. To effectively translate this feature into the clinic, especially via oral or parenteral administration, a thorough understanding of the interactions of the micro- and nanosized material with the physiological environment during the delivery process is required. In the present study, the behaviour of thermally oxidized porous silicon particles of different sizes interacting with Caco-2 cells (both non-differentiated and polarized monolayers) was investigated in order to establish their fate in a model of intestinal epithelial cell barrier. Particle interactions and TNF-α were measured in RAW 264.7 macrophages, while cell viabilities, reactive oxygen species and nitric oxide levels, together with transmission electron microscope images of the polarized monolayers, were assessed with both the Caco-2 cells and RAW 264.7 macrophages. The results showed a concentration and size dependent influence on cell viability and ROS-, NO- and TNF-α levels. There was no evidence of the porous nanoparticles crossing the Caco-2 cell monolayers, yet increased permeation of the loaded poorly soluble drug, griseofulvin, was shown.

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KW - griseofulvin

KW - humans

KW - inflammation

KW - intestines

KW - intracellular space

KW - macrophages

KW - mice

KW - nanoparticles

KW - nitric oxide

KW - oxidation-reduction

KW - porosity

KW - reactive oxygen species

KW - silicon

KW - solubility

KW - temperature

KW - tumor necrosis factor-alpha

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U2 - 10.1016/j.biomaterials.2010.12.011

DO - 10.1016/j.biomaterials.2010.12.011

M3 - Article

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VL - 32

SP - 2625

EP - 2633

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 10

ER -