title: Enhanced anti-tumor effect of 9-nitro-camptothecin complexed by hydroxypropyl-β-cyclodextrin and safety evaluation.
abstract: The aim of this study was to evaluate the safety and anti-tumor effect of 9-nitro-camptothecin/hydroxypropyl-β-cyclodextrin (9-NC/HP-β-CD) complex on tumor-bearing mice. The in vitro anti-tumor activity was tested by MTT assay. Our study revealed that the 9-NC/HP-β-CD complex showed significant anti-tumor activity towards Skov-3, MCF-7, HeLa and S180 cell lines with IC(50) values of 0.24 ± 0.09, 0.59 ± 0.20, 0.83 ± 0.11, and 6.30 ± 2.42 μg/ml, respectively, significantly superior to the free 9-NC. The in vivo therapeutic efficacy was investigated in ICR mice bearing mouse sarcoma S180. Both the high (3mg/kg) and low (1mg/kg) doses of 9-NC/HP-β-CD complex demonstrated high inhibition ratio of tumor growth (>75%). The subacute toxicity test was performed by measuring the body weight, histopathology, blood cell counts and clinical chemistry parameters (total bilirubin, alanine transferase, aspartate transferase, blood urea nitrogen and creatinine), and the results indicated the good safety profile of the complex. Taken together, the results suggested that the 9-NC complexed in HP-β-CD, instead of dissolved in the organic solvent, presented significant anti-tumor activity and low toxicity for the treatment of cancer.
authors.affiliation: School of Pharmacy, Fudan University, # 826, Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xinyi
authors.initials: X
authors.lastname: Jiang
authors.forename: Kitki
authors.initials: K
authors.lastname: Law
authors.forename: Yanzuo
authors.initials: Y
authors.lastname: Chen
authors.forename: Jijin
authors.initials: J
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xin
authors.forename: Xianyi
authors.initials: X
authors.lastname: Sha
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008813:Mice, Inbred ICR; D012510:Sarcoma 180 / Q000188:drug therapy / Q000473:pathology; D036401:Toxicity Tests, Chronic; D023041:Xenograft Model Antitumor Assays; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C079905:rubitecan; D002166:Camptothecin