In-vivo anti-tumor activity of a novel poloxamer-based thermosensitive in situ gel for sustained delivery of norcantharidin

Abstract

In order to develop a novel norcantharidin (NCTD) delivery system with slow drug release and specific targeting characteristics, we have developed a Poloxamer-based NCTD thermosensitive in situ gel. The evaluation of the characteristics of this system using both in vitro and in vivo methods was previously reported. However, its anti-tumor activity in vivo is still not confirmed. Thus, the potential anti-tumor activity and relative mechanism were investigated in a murine H22 hepatoma model. Tumor-bearing mice were treated with different dose of NCTD thermosensitive in situ gel (3.3 mg/kg, 6.6 mg/kg, and 9.9 mg/kg, respectively by intra-tumor injection once every three days, totaling 5 injections per group. Control groups included untreated or NCTD injection (2.2 mg/kg, qd) or blank in situ gel. The expression of vascular endothelial growth factor (VEGF) and CD44 in tumor tissue was examined by immunohistochemistry (IHC) staining. Treatment with middle or high dose of NCTD thermosensitive in situ gel significantly induced tumor regression, inhibited VEGF and CD44 expression and improved survival of tumor-bearing mice. The efficacy of NCTD thermosensitive in situ gel is higher than that of free NCTD injection. Therefore, NCTD thermosensitive in situ gel is a novel NCTD delivery approach for chemotherapeutic treatment of cancer.

Keywords:

• Anti-hepatoma
• norcantharidin
• vascular endothelial growth factor
• intratumoral injection

Acknowledgements

The discussion of this article was helped by Professor Gao Jianqing, College of Pharmaceutical Sciences, Zhejiang University. The revision of this article was helped by Doctor Zhang Tianyuan, College of Pharmaceutical Sciences, Zhejiang University. The revision of Figure 2 and Figure 3 was helped by Pathologist Huang Yan, Department of Pathology, First People’s Hospital of Yuhang District, Hangzhou, Zhejiang.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was financially supported by the Science and Technology Project of Yuhang District, Hangzhou City (2014003), Science and Technology Project of Hangzhou City (Social Development) (20140633B57), Health Science and Technology Project of Hangzhou City (2015B32), Science and Technology Project of Hangzhou City (Agriculture and Social Development) (2016007), Science and Technology Project of Yuhang District, Hangzhou City (2017002),Natural Science Foundation of Zhejiang Province of China (LQ14H280003).