A moderate interaction of maltosyl-alpha-cyclodextrin with Caco-2 cells incomparison with the parent cyclodextrin

The cytotoxicity of maltosyl-alpha -cyclodextrin (G(2)-alpha -CyD) and malt osyl-beta -cyclodextrin (G(2)-beta -CyD) toward Caco-2 cells was compared w ith that of natural beta -cyclodeltrin (alpha CyD), beta -cyclodestrin (bet a -CyD) and gamma -cyclodextrin (gamma -CyD). The degree of increase In cyt otoxicity was dependent on the CyD's type and the concentration: the cytoto xicity of CyDs at the same concentration increased in the order of gamma -C yD<G(2)-<beta>-CyD<G(2)-<alpha>-CyD much less than alpha -CyD , although be ta -CyD could not be compared to other CyDs because of low solubility in wa ter, alpha -CyD decreased transepithelial electrical resistance (TEER) and increased the apical-to-basolateral (AP-to-BL) transport of [H-3]mannitol, a paracellular transport marker, in a concentration-deprendent manner, sugg esting that alpha -CyD decreased the integrity of Caco-2 cell monolayers. I n addition, alpha -CyD increased the AP-to-BL transport of rhodaminc 123, a transcellular transport marker; under the experimental conditions being in dependent of P-glycoprotein. In contrast, G(2)-alpha -CyD, G(2)-beta -CyD a nd gamma -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 G(2)-alpha -CyD and G(2)-beta -CyD for effect TEER and the tra nsport of mannitol and rhodamine 123 could be explained by the findings tha t these maltosylated CyDs released only a small amount of membrane constitu ents from Caco-2 cell monolayers and interacted only weakly with monolayers composed of L-alpha -dipalmitoylphosphatidylcholine (DPPC) formed on water . These results Indicate that G(2)-alpha -CyD has less cytotoxicity and les s disturbing ability toward Caco-2 cell monolayers than alpha -CSD, and G(2 )-beta -CyD has, at least, comparable cytotoxicity to beta -CyD toward them , Thus, from the safety point of view, highly water soluble G(2)-alpha -CyD and G(2)-beta -CyD may be particularly useful in various pharmaceutical fo rmulations.