摘要：The cytotoxicity of maltosyl-α-cyclodextrin (G2-α-CyD) and maltosyl-β-cyclodextrin (G2-β-CyD) toward Caco-2 cells was compared with that of natural α-cyclodextrin (α-CyD), β-cyclodextrin (β-CyD) and γ-cyclodextrin (γ-CyD). The degree of increase in cytotoxicity was dependent on the CyD’s type and the concentration: the cytotoxicity of CyDs at the same concentration increased in the order of γ-CyD2-β-CyD2-α-CyD<<α-CyD, although β-CyD could not be compared to other CyDs because of low solubility in water. α-CyD decreased transepithelial electrical resistance (TEER) and increased the apical-to-basolateral (AP-to-BL) transport of [3H]mannitol, a paracellular transport marker, in a concentration-dependent manner, suggesting that α-CyD decreased the integrity of Caco-2 cell monolayers. In addition, α-CyD increased the AP-to-BL transport of rhodamine 123, a transcellular transport marker, under the experimental conditions being independent of P-glyco-protein. In contrast, G2-α-CyD, G2-β-CyD and γ-CyD had slight effect on both TEER and the transport of mannitol and rhodamine 123 even at relatively high concentrations up to 150 mM. The inability of G2-α-CyD and G2-β-CyD to effect TEER and the transport of mannitol and rhodamine 123 could be explained by the findings that these maltosylated CyDs released only a small amount of membrane constituents from Caco-2 cell monolayers and interacted only weakly with monolayers composed of L-α-dipalmitoylphosphatidylcholine (DPPC) formed on water. These results indicate that G2-α-CyD has less cytotoxicity and less disturbing ability toward Caco-2 cell monolayers than α-CyD, and G2-β-CyD has, at least, comparable cytotoxicity to β-CyD toward them. Thus, from the safety point of view, highly water-soluble G2-α-CyD and G2-β-CyD may be particularly useful in various pharmaceutical formulations.
