Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery

Jurja C Coyuco, Yuanjie Liu, Bee-Jen Tan, Gigi NC ChiuDepartment of Pharmacy, Faculty of Science, National University of Singapore, SingaporeAbstract: Although carbon nanomaterials (CNMs) have been increasingly studied for their biomedical applications, there is limited research on these novel mater...

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Autores principales:	Coyuco JC, Liu Y, Tan BJ, Chiu GNC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/14be225652944b3d90bd8c34c3fc227e
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spelling	oai:doaj.org-article:14be225652944b3d90bd8c34c3fc227e2021-12-02T07:51:44ZFunctionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery1176-91141178-2013https://doaj.org/article/14be225652944b3d90bd8c34c3fc227e2011-10-01T00:00:00Zhttp://www.dovepress.com/functionalized-carbon-nanomaterials-exploring-the-interactions-with-ca-a8434https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Jurja C Coyuco, Yuanjie Liu, Bee-Jen Tan, Gigi NC ChiuDepartment of Pharmacy, Faculty of Science, National University of Singapore, SingaporeAbstract: Although carbon nanomaterials (CNMs) have been increasingly studied for their biomedical applications, there is limited research on these novel materials for oral drug delivery. As such, this study aimed to explore the potential of CNMs in oral drug delivery, and the objectives were to evaluate CNM cytotoxicity and their abilities to modulate paracellular transport and the P-glycoprotein (P-gp) efflux pump. Three types of functionalized CNMs were studied, including polyhydroxy small-gap fullerenes (OH-fullerenes), carboxylic acid functionalized single-walled carbon nanotubes (fSWCNT-COOH) and poly(ethylene glycol) functionalized single-walled carbon nanotubes (fSWCNT-PEG), using the well-established Caco-2 cell monolayer to represent the intestinal epithelium. All three CNMs had minimum cytotoxicity on Caco-2 cells, as demonstrated through lactose dehydrogenase release and 3-(4,5-dimethyliazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Of the three CNMs, fSWCNT-COOH significantly reduced transepithelial electrical resistance and enhanced transport of Lucifer Yellow across the Caco-2 monolayer. Confocal fluorescence microscopy showed that fSWCNT-COOH treated cells had the highest perturbation in the distribution of ZO-1, a protein marker of tight junction, suggesting that fSWCNT-COOH could enhance paracellular permeability via disruption of tight junctions. This modulating effect of fSWCNT-COOH can be reversed over time. Furthermore, cellular accumulation of the P-gp substrate, rhodamine-123, was significantly increased in cells treated with fSWCNT-COOH, suggestive of P-gp inhibition. Of note, fSWCNT-PEG could increase rhodamine-123 accumulation without modifying the tight junction. Collectively, these results suggest that the functionalized CNMs could be useful as modulators for oral drug delivery, and the differential effects on the intestinal epithelium imparted by different types of CNMs would create unique opportunities for drug-specific oral delivery applications.Keywords: fullerenes, carbon nanotubes, functionalization, paracellular transport, P-glycoproteinCoyuco JCLiu YTan BJChiu GNCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2253-2263 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Coyuco JC Liu Y Tan BJ Chiu GNC Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery
description	Jurja C Coyuco, Yuanjie Liu, Bee-Jen Tan, Gigi NC ChiuDepartment of Pharmacy, Faculty of Science, National University of Singapore, SingaporeAbstract: Although carbon nanomaterials (CNMs) have been increasingly studied for their biomedical applications, there is limited research on these novel materials for oral drug delivery. As such, this study aimed to explore the potential of CNMs in oral drug delivery, and the objectives were to evaluate CNM cytotoxicity and their abilities to modulate paracellular transport and the P-glycoprotein (P-gp) efflux pump. Three types of functionalized CNMs were studied, including polyhydroxy small-gap fullerenes (OH-fullerenes), carboxylic acid functionalized single-walled carbon nanotubes (fSWCNT-COOH) and poly(ethylene glycol) functionalized single-walled carbon nanotubes (fSWCNT-PEG), using the well-established Caco-2 cell monolayer to represent the intestinal epithelium. All three CNMs had minimum cytotoxicity on Caco-2 cells, as demonstrated through lactose dehydrogenase release and 3-(4,5-dimethyliazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Of the three CNMs, fSWCNT-COOH significantly reduced transepithelial electrical resistance and enhanced transport of Lucifer Yellow across the Caco-2 monolayer. Confocal fluorescence microscopy showed that fSWCNT-COOH treated cells had the highest perturbation in the distribution of ZO-1, a protein marker of tight junction, suggesting that fSWCNT-COOH could enhance paracellular permeability via disruption of tight junctions. This modulating effect of fSWCNT-COOH can be reversed over time. Furthermore, cellular accumulation of the P-gp substrate, rhodamine-123, was significantly increased in cells treated with fSWCNT-COOH, suggestive of P-gp inhibition. Of note, fSWCNT-PEG could increase rhodamine-123 accumulation without modifying the tight junction. Collectively, these results suggest that the functionalized CNMs could be useful as modulators for oral drug delivery, and the differential effects on the intestinal epithelium imparted by different types of CNMs would create unique opportunities for drug-specific oral delivery applications.Keywords: fullerenes, carbon nanotubes, functionalization, paracellular transport, P-glycoprotein
format	article
author	Coyuco JC Liu Y Tan BJ Chiu GNC
author_facet	Coyuco JC Liu Y Tan BJ Chiu GNC
author_sort	Coyuco JC
title	Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery
title_short	Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery
title_full	Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery
title_fullStr	Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery
title_full_unstemmed	Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery
title_sort	functionalized carbon nanomaterials: exploring the interactions with caco-2 cells for potential oral drug delivery
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/14be225652944b3d90bd8c34c3fc227e
work_keys_str_mv	AT coyucojc functionalizedcarbonnanomaterialsexploringtheinteractionswithcaco2cellsforpotentialoraldrugdelivery AT liuy functionalizedcarbonnanomaterialsexploringtheinteractionswithcaco2cellsforpotentialoraldrugdelivery AT tanbj functionalizedcarbonnanomaterialsexploringtheinteractionswithcaco2cellsforpotentialoraldrugdelivery AT chiugnc functionalizedcarbonnanomaterialsexploringtheinteractionswithcaco2cellsforpotentialoraldrugdelivery
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Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery

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