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Biochim Biophys Acta. 2014 Mar;1840(3):1171-80. doi: 10.1016/j.bbagen.2013.12.014. Epub 2013 Dec 19.

Physicochemical properties and in vitro intestinal permeability properties and intestinal cell toxicity of silica particles, performed in simulated gastrointestinal fluids.

Author information

1
Division of Drugs, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. Electronic address: kumikato@nihs.go.jp.
2
Division of Drugs, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
3
National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.

Abstract

BACKGROUND:

Amorphous silica particles with the primary dimensions of a few tens of nm, have been widely applied as additives in various fields including medicine and food. Especially, they have been widely applied in powders for making tablets and to coat tablets. However, their behavior and biological effects in the gastrointestinal tracts associated with oral administration remains unknown.

METHODS:

Amorphous silica particles with diameters of 50, 100, and 200nm were incubated in the fasted-state and fed-state simulated gastric and intestinal fluids. The sizes, intracellular transport into Caco-2 cells (model cells for intestinal absorption), the Caco-2 monolayer membrane permeability, and the cytotoxicity against Caco-2 cells were then evaluated for the silica particles.

RESULTS:

Silica particles agglomerated in fed-state simultaneous intestinal fluids. The agglomeration and increased particles size inhibited the particles' absorption into the Caco-2 cells or particles' transport through the Caco-2 cells. The in vitro cytotoxicity of silica particles was not observed when the average size was larger than 100nm, independent of the fluid and the concentration.

CONCLUSION:

Our study indicated the effect of diet on the agglomeration of silica particles. The sizes of silica particles affected the particles' absorption into or transport through the Caco-2 cells, and cytotoxicity in vitro, depending on the various biological fluids.

GENERAL SIGNIFICANCE:

The findings obtained from our study may offer valuable information to evaluate the behavior of silica particles in the gastrointestinal tracts or safety of medicines or foods containing these materials as additives.

KEYWORDS:

DDS; DMEM; Dulbecco's modified Eagle's medium; FBS; FaSSGF; FaSSIF; FeSSGF; FeSSIF; HBSS; Hanks' balanced salt solution; In vitro model; Nanomaterial; PBS; PDI; Phosphate buffer saline; Silica particle; Simulated gastrointestinal fluid; TEER; TEM; drug delivery system; fasted-state simulated gastric fluids; fasted-state simulated intestinal fluids; fed-state simulated gastric fluids; fed-state simulated intestinal fluids; fetal bovine serum; polydispersity index; transepithelial electrical resistance; transmission electron microscopy

PMID:
24361607
DOI:
10.1016/j.bbagen.2013.12.014
[Indexed for MEDLINE]
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