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Acta Biochimica et Biophysica Sinica Advance Access originally published online on May 27, 2009
Acta Biochimica et Biophysica Sinica 2009 41(7):578-587; doi:10.1093/abbs/gmp045
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Study on docetaxel-loaded nanoparticles with high antitumor efficacy against malignant melanoma

Donghui Zheng1,{dagger}, Xiaolin Li2,{dagger}, Huae Xu3,{dagger}, Xiaowei Lu4, Yong Hu5 and Weixin Fan1,*

1 Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
2 Department of Oncology, Drum Tower Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China
3 Department of Pharmacy, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
4 Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
5 National Laboratory of Solid State Microstructure, Department of Material Science and Engineering, Nanjing University, Nanjing 210093, China

* Correspondence address. Tel: +86-25-86415357; Fax: +86-25-86415357; E-mail: weixinfannj{at}yahoo.cn


  Abstract

Docetaxel (Doc) has extraordinary activities against a variety of solid tumors. However, the clinical efficacy of Doc is limited due to its poor solubility, low selective distribution, fast elimination in vivo, etc. In the present study, Doc was incorporated into the core-shell structure of nanoparticles prepared based on our previous work. The obtained docetaxel-loaded nanoparticles (DOCNP) were characterized with various biophysical methodologies, and its antitumor efficacy against malignant melanoma was evaluated both in vitro and in vivo. Our results indicated that Doc could be incorporated into the nanoparticles with high encapsulation efficiency (>90%). The incorporated Doc can be released from DOCNP in a sustained manner. In vitro cytotoxicity studies indicated that DOCNP could effectively kill B16 cells and show a dose- and time-dependent efficacy. Furthermore, intratumoral administration revealed that DOCNP has significantly higher antitumor effect and lower toxicity to normal cells and tissues than free Doc. These results suggest that DOCNP may be a promising drug delivery system in therapy for malignant melanoma.

Keywords    docetaxel; nanoparticle; melanoma; controlled release

Received: March 20, 2009; Accepted: April 7, 2009

{dagger} These authors contributed equally to this work.


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