Preparation, pharmacokinetics, tissue distribution and antitumor effect of sorafenib‑incorporating nanoparticles in vivo

Sheng,Xia; Huang,Tao; Qin,Jianmin; Li,Qi; Wang,Weiwei; Deng,Liandong; Dong,Anjie

doi:10.3892/ol.2017.6934

Preparation, pharmacokinetics, tissue distribution and antitumor effect of sorafenib‑incorporating nanoparticles in vivo

Authors:
- Xia Sheng
- Tao Huang
- Jianmin Qin
- Qi Li
- Weiwei Wang
- Liandong Deng
- Anjie Dong
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Affiliations: Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China, Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China, Institute of Chemical Industry, Tianjin University, Tianjin 300072, P.R. China
Published online on: September 14, 2017 https://doi.org/10.3892/ol.2017.6934
Pages: 6163-6169

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Abstract

Sorafenib is a molecularly targeted drug used for treating hepatocellular carcinoma. However, sorafenib may affect the function of normal hepatocytes, and the clinical application of sorafenib is limited due to its adverse effects. The aim of the current study was to improve the effectiveness of sorafenib by preparing it as a nanoparticle formulation using nanoprecipitation technology. Sorafenib was combined with a polyethylene glycol monomethyl ether‑racemic polylactic acid copolymer. The properties of the nanoparticles, including particle size, ξ potential and release efficiency, were measured. The pharmacokinetic profile, tissue distribution and tumor‑inhibiting effects of the nanoparticles were determined in vitro and in vivo. Compared with sorafenib, the nanoparticle formulation exhibited a significant increase in in vivo retention time. The concentration of sorafenib in tumor tissues was significantly higher than that in normal tissues following treatment with sorafenib nanoparticles. Sorafenib nanoparticles were more efficacious in inhibiting tumor growth compared with sorafenib alone. The results, provided they can be extended to humans, suggest that sorafenib nanoparticles may specifically target hepatocellular carcinoma.

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