| Autor: |
Nagase, Yukihiko, Arima, Hidetoshi, Wada, Koki, Sugawara, Tadaki, Satoh, Hiroshi, Hirayama, Fumitoshi, Uekama, Kaneto |
| Zdroj: |
Journal of Pharmaceutical Sciences; December 2003, Vol. 92 Issue: 12 p2466-2474, 9p |
| Abstrakt: |
The effects of water‐soluble β‐cyclodextrin derivatives (β‐CyDs), such as 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CyD) and sulfobutyl ether β‐cyclodextrin (SBE7‐β‐CyD) on cytotoxicity of DY‐9760e (3‐[2‐[4‐(3‐chloro‐2‐methylphenyl)‐1‐piperazinyl]ethyl]‐5,6‐dimethoxy‐1‐(4‐imidazolylmethyl)‐1H‐indazole dihydrochloride 3.5 hydrate) toward human umbilical vein endothelial cells (HUVECs) in vitroand vascular damage of the auricular vein of rabbits by DY‐9760e in vivowere investigated. The spectroscopic study revealed that of the four β‐CyDs SBE7‐β‐CyD forms the most stable inclusion complex in phosphate‐buffered saline, probably because of a synergetic effect of hydrophobic and electrostatic interactions. β‐CyDs inhibited DY‐9760e‐induced cell death toward HUVECs in an order of G2‐β‐CyD < β‐CyD < HP‐β‐CyD < SBE7‐β‐CyD, which was consistent with the order of the magnitude of stability constants. When the DY‐9760e solution was infused into the auricular vein of rabbits for 24 h, SBE7‐β‐CyD suppressed a DY‐9760e‐induced irritation such as thrombus, desquamation of the endothelium vasculitis, and perivasculitis. The present data indicated that SBE7‐β‐CyD formed an inclusion complex with DY‐9760e in a buffer solution and possessed the protective effect on DY‐9760e‐induced cytotoxicity toward HUVECs and vascular damage in rabbits. These results suggested potential use of SBE7‐β‐CyD as a parenteral carrier for DY‐9760e. © 2003 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2466–2474, 2003 |
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