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Lowering of sodium deoxycholate-induced nasal ciliotoxicity with cyclodextrins
1Division of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Aim:
To lower the nasal ciliotoxicity of sodium deoxycholate (SDC) in combination with cyclodextrins (CD).
Methods:
The erythrocyte hemolysis test was carried out to evaluate the damaging effect of SDC on the erythrocyte membrane. The in situ toad palate model and scanning electron microscope technique were used to investigate the nasal ciliotoxicity of SDC solution in combination with CD. The inclusion effect between SDC and beta-cyclodextrin (beta-CD) was studied by differential thermal analysis (DTA) and X-ray diffractometry.
Results:
The hemolysis test showed that beta-CD and dimethyl-beta-cyclodextrin (DM-beta-CD) could effectively protect the erythrocyte membrane against damage by SDC at the molar ratios of 1:1 and 2:1. When SDC combined with beta-CD or DM-beta-CD at a molar ratio of 1:2 or 1:3, the ciliotoxicity of SDC was greatly alleviated and the percent lasting time of the ciliary movement increased to 50 % or above. Scanning electron microscope investigations showed that SDC combined with beta-CD at a molar ratio 1:2 had no marked damage on the rat nasal mucosa after nasal administration thrice a day for a week. DTA and X-ray diffractometry investigations showed that SDC formed an inclusion with beta-CD.
Conclusion:
Combining beta-CD or DM-beta-CD with SDC can greatly lower the hemolytic effect and ciliotoxicity of SDC and the optimal molar ratio of SDC to CD is 1:2. Such protection provided by CD is due to the inclusion effect between SDC and CD.