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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Dodecylphosphocholine-mediated enhancement of paracellular permeability and cytotoxicity in Caco-2 cell monolayers.

The intestinal epithelium is a significant barrier for oral absorption of hydrophilic drugs because they cannot easily traverse the lipid bilayer of the cell membrane and their passage through the intercellular space (paracellular transport) is restricted by the tight junctions. In this report we show that dodecylphosphocholine (DPC) can improve the paracellular permeability of hydrophilic compounds across Caco-2 cell monolayers by modulating the tight junctions. The results show that the alkyl chain as well as the zwitterionic head group of DPC are required for its activity. DPC appears to act by modulating the permeability of tight junctions as evidenced by the fact that treatment of Caco-2 cell monolayers by this agent results in a decreased transepithelial electrical resistance (TEER), increased permeability of paracellular markers (e. g., mannitol) with no change in the permeability of the transcellular marker testosterone, and redistribution of the tight junction-associated protein ZO-1. The effect of DPC on Caco-2 cells (e.g., decrease in TEER) is reversible, and is not caused by gross cytotoxicity (as indicated by the MTT test) or by nonspecific disruption of the cell membrane (as indicated by only slight nuclear staining due to the nonpermeable DNA-specific dye propidium iodide). We propose in the present study a parameter, potency index, that allows comparison of various enhancers of paracellular transport in relation to their cytotoxicity. The potency index is a ratio between the IC(50) value (concentration at which 50% inhibition of control mitochondrial dehydrogenase activity occurs in the MTT test) and the EC(50) value (concentration at which TEER drops to 50% of its control (untreated) value). By this parameter, DPC is significantly safer than the commonly used absorption enhancer palmitoyl carnitine (PC), which has the potency index of approximately 1 (i.e., no separation between effective and toxic concentration).[1]


  1. Dodecylphosphocholine-mediated enhancement of paracellular permeability and cytotoxicity in Caco-2 cell monolayers. Liu, D.Z., LeCluyse, E.L., Thakker, D.R. Journal of pharmaceutical sciences. (1999) [Pubmed]
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