Enhanced anti-tumor effect of 9-nitro-camptothecin complexed by hydroxypropyl-β-cyclodextrin and safety evaluation

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 IC50 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 (3 mg/kg) and low (1 mg/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.

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► We have developed a novel HP-β-CD-based formulation for the delivery of 9-NC.
► 9-NC complexedin HP-β-CD presented significant anti-tumor activity both in vivo and in vitro.
► The complex ameliorated lymphocytopenia and reduced hematological toxicityin mice.
► Complexation with HP-β-CDreduced the liver toxicity and nephrotoxicity of the free 9-NC solution.