title: Comparison in toxicity and solubilizing capacity of hydroxypropyl-β-cyclodextrin with different degree of substitution.
abstract: Hydroxypropyl-β-cyclodextrin (HP-β-CD) has been widely used as an effective solubilizing agent in pharmaceutical industry for many years. However, the effect of degree of substitution (D.S.) of HP-β-CD on solubilizing capacity and toxicity has not been concerned. In this study, solubilizing capacity of HP-β-CDs with three different D.S. (4.55, 6.16 and 7.76) for 16 drugs were measured and their toxicities were compared by a 7-day i.v. administration (q.d.) study in rats. Generally, HP-β-CD with high D.S. (7.76) showed weaker solubilizing capacity for steroids and BCS class II drugs, but lower hemolytic activity, compared with that of HP-β-CD with low (4.55) or medium (6.16) D.S. HP-β-CD with low D.S. resulted in more changes in hematological and biochemical parameters, but the effects were reversible after a 7-day recovery. Moreover, HP-β-CD with medium D.S. may have slightly greater nephrotoxicity than the other two HP-β-CDs. HP-β-CDs with different D.S. had similar urine excretion percentage after i.v. administration and none of them was found to affect glomerular filtration function of rats. The results suggest that HP-β-CD with low D.S. would be a better choice considering both the solubilizing capacity and toxicity. However, comparison in toxicity of HP-β-CDs with different D.S. should be carried out in human in view of its species-dependence property.
authors.affiliation: Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Li
authors.affiliation: Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.affiliation: Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Ni
authors.affiliation: Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Guangzhou Cellprotek Pharmaceutical Co., Ltd, Guangzhou 510663, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wen
authors.affiliation: Guangzhou Cellprotek Pharmaceutical Co., Ltd, Guangzhou 510663, China.
authors.forename: Qiuyun
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Yuanna
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Pengxin
authors.initials: P
authors.lastname: Qiu
authors.affiliation: Guangzhou Cellprotek Pharmaceutical Co., Ltd, Guangzhou 510663, China.
authors.forename: Suizhen
authors.initials: S
authors.lastname: Lin
authors.affiliation: Lab of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: lsshhy@mail.sysu.edu.cn.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D004912:Erythrocytes / Q000187:drug effects; D005079:Excipients / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D008297:Male; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin
keywords: Degree of substitution; Hydroxypropyl-β-cyclodextrin; Solubilizing capacity; Toxicity