Abstract
Titanate nanotubes can be used as drug delivery systems, but limited information is available on their interactions with intestinal cells. In this study, we investigated the cytotoxicity and cellular uptake of titanate nanotubes on Caco-2 monolayers and found that up to 5 mg/ml concentration, these nanotubes are not cytotoxic and not able to permeate through the intestinal cell layer. Transmission electron microscopic experiments showed that titanate nanotubes are not taken up by cells, only caused a high-density granulation on the surface of the endoplasmic reticulum. According to these results, titanate nanotubes are suitable systems for intestinal drug delivery.
References
Chen P, Lin J, Tan KL. Carbon nanotubes: a future material of life. IUBMB Life. 2000;49(2):105–8.
Kasuga T, Hiramatsu M, Hoson A, Sekino T, Niihara K. Formation of titanium oxide nanotube. Langmuir. 1998;14:3160–3.
Li Y, Wang T, Wang J, Jiang T, Cheng G, Wang S. Functional and unmodified MWNTs for delivery of the water-insoluble drug carvedilol—a drug-loading mechanism. Appl Surf Sci. 2011;257(13):5663–70.
Im JS, Bai BC, Lee YS. The effect of carbon nanotubes on drug delivery in an electrosensitive transdermal drug delivery system. Biomater. 2010;31(6):1414–9.
Naficy S, Razal JM, Spinks GM, Wallace GG. Modulated release of dexamethasone from chitosan-carbon nanotube films. Sens Actuators A. 2009;155(1):120–4.
Sayes CM, Liang F, Hudson JL, Mendez J, Guo W, Beach JM, et al. Functionalization density dependence of single walled carbon nanotubes cytotoxicity in vitro. Toxicol Lett. 2006;161(2):135–42.
Horváth E, Kukovecz Á, Kónya Z, Kiricsi I. Hydrothermal conversion of self-assembled TiNT into nanowires in a revolving autoclave. Chem Mater. 2007;19:927–31.
Kukovecz Á, Hodos M, Horváth E, Radnóczi G, Kónya Z, Kiricsi I. Oriented crystal growth model explains the formation of titania nanotubes. J Phys Chem B. 2005;109:17781–3.
Fenyvesi F, Kiss T, Fenyvesi É, Szente L, Veszelka S, Deli MA, et al. Randomly methylated β-cyclodextrin derivatives enhance taxol permeability through human intestinal epithelial Caco-2 cell monolayer. J Pharm Sci. 2011;100(11):4734–44.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.
Koeneman BA, Zhang Y, Westerhoff P, Chen Y, Crittenden JC, David G, et al. Toxicity and cellular responses of intestinal cells exposed to titanium dioxide. Cell Biol Toxicol. 2010;26:225–38.
Wadhawa S, Rea C, O’Hare P, Mathur A, Roy SS, Dunlop PSM, et al. Comparative in vitro cytotoxicity study of carbon nanotubes and titania nanostructures on human lung epithelial cells. J Hazard Mater. 2011;191:56–61.
Fotakis G, Timbrell JA. In vitro cytotoxicity assays. Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Tox Lett. 2006;160:171–7.
Konsoula R, Barile FA. Correlation of in vitro cytotoxicity with paracellular permeability in Caco-2 cells. Toxicol in Vitro. 2005;19:675–84.
Wang Z, Sun Y, Wang D, Liu H, Boughton IR. In situ fabrication of silver nanoparticle-filled hydrogen titanate nanotube layer on metallic titanium surface for bacteriostatic and biocompatible implantation. Int J Nanomed. 2013;8:2903–16.
Zennaro L, Magro M, Vianello F, Rigo A, Mariotto G, Giarola M, et al. Stable aqueous solutions of naked nanotubes. ChemPhysChem. 2013;14:2786–92.
Acknowledgments
This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP-4.2.2.A-11/1/KONV-2012-0047 and TÁMOP 4.2.4. A/2-11-1-2012-0001 “National Excellence Program—Elaborating and operating an inland student and researcher personal support system”.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fenyvesi, F., Kónya, Z., Rázga, Z. et al. Investigation of the Cytotoxic Effects of Titanate Nanotubes on Caco-2 Cells. AAPS PharmSciTech 15, 858–861 (2014). https://doi.org/10.1208/s12249-014-0115-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-014-0115-x