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Title: Functionalized carbon nanomaterials: Exploring the interactions with Caco-2 cells for potential oral drug delivery
Authors: Coyuco, J.C.
Liu, Y.
Tan, B.-J. 
Chiu, G.N.C. 
Keywords: Carbon nanotubes
Paracellular transport
Issue Date: 2011
Citation: Coyuco, J.C., Liu, Y., Tan, B.-J., Chiu, G.N.C. (2011). Functionalized carbon nanomaterials: Exploring the interactions with Caco-2 cells for potential oral drug delivery. International Journal of Nanomedicine 6 (1) : 2253-2263. ScholarBank@NUS Repository.
Abstract: 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 (f SWCNT-COOH) and poly(ethylene glycol) functionalized single-walled carbon nanotubes (f SWCNT-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, f SWCNT-COOH significantly reduced transepithelial electrical resistance and enhanced transport of Lucifer Yellow across the Caco-2 monolayer. Confocal fluorescence microscopy showed that f SWCNT-COOH treated cells had the highest perturbation in the distribution of ZO-1, a protein marker of tight junction, suggesting that f SWCNT-COOH could enhance paracellular permeability via disruption of tight junctions. This modulating effect of f SWCNT-COOH can be reversed over time. Furthermore, cellular accumulation of the P-gp substrate, rhodamine-123, was significantly increased in cells treated with f SWCNT-COOH, suggestive of P-gp inhibition. Of note, f SWCNT-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. © 2011 Coyuco et al, publisher and licensee Dove Medical Press Ltd.
Source Title: International Journal of Nanomedicine
ISSN: 11769114
DOI: 10.2147/IJN.S23962
Appears in Collections:Staff Publications

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