Cytotoxicity study of ordered mesoporous silica MCM-41 and SBA-15 microparticles on Caco-2 cells

Teemu Heikkilä*, Hélder A. Santos, Narendra Kumar, Dmitry Yu Murzin, Jarno Salonen, Timo Laaksonen, Leena Peltonen, Jouni Hirvonen, Vesa Pekka Lehto

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

68 Citations (Scopus)

Abstract

Cytotoxicity of ordered mesoporous silica MCM-41 and SBA-15 microparticles (fractions between 1 and 160 μm) was determined in vitro on undifferentiated human colon carcinoma (Caco-2) cell line, considering the feasibility of using these silica-based materials in oral drug formulations. The cellular endpoints employed for assessing the effects of the MCM-41 and SBA-15 microparticles on Caco-2 were: (1) cell membrane integrity by monitoring live-cell protease activity (AFC) and by employing the flow cytometry method; (2) metabolic activity by monitoring total ATP content via luminescence assay; (3) activity of apoptotic effectors by caspase-3/7 activity assay. The generation of reactive oxygen species (ROS) was also followed, specifically the hydrogen peroxide (H2O2) and the superoxide radical (O2{radical dot} -). MCM-41 and SBA-15 microparticles caused cytotoxic effects on the Caco-2 cells, at most tested concentrations (0.2-14 mg/ml) and incubation times (3 and 24 h). The effects on the cells included weakened cell membrane integrity, diminished cell metabolism and increased apoptotic signalling. The root cause for the cytotoxicity was heightened production of reactive oxygen species (ROS), especially the formation of the superoxide radical O2{radical dot} - already after 3 h incubation with threshold dose 1 mg/ml, apparently overwhelming the antioxidant defences and causing mitochondrial dysfunction, hence increasing the apoptotic signalling.

Original languageEnglish
Pages (from-to)483-494
Number of pages12
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume74
Issue number3
DOIs
Publication statusPublished - Mar 2010
MoE publication typeA1 Journal article-refereed

Keywords

  • Biocompatibility
  • Caco-2
  • Cell viability
  • Cytotoxicity
  • Mesoporous silica
  • Microparticle
  • Oral drug delivery

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