Original Articles
Copyright ©The Author(s) 1999. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 15, 1999; 5(6): 511-514
Published online Dec 15, 1999. doi: 10.3748/wjg.v5.i6.511
Study on the anticarcinogenic effect and acute toxicity of liver-targeting mitoxantrone nanoparticles
Zhi-Rong Zhang, Qin He, Gong-Tie Liao, Shao-Huai Bai
Zhi-Rong Zhang, Qin He, Gong-Tie Liao, Shao-Huai Bai, School of Pharmacy, West China University of Medical Sciences, Chengdu 6 10041, Sichuan Province, P.R. China
Zhi-Rong Zhang, male, 43 years old, graduated from West China Unive rsity of Medical Sciences (WCUMS) as a Ph.D. in 1993. Professor of pharmaceutics , Dean of the School of Pharmacy of WCUMS, member of Chinese Pharmacopoiea Commi ssion, council member of Chinese Pharmaceutical Association (CPA), member of Society of Pharmaceutics of CPA, specializes in targeted delivery system and has mo re than 80 papers and 6 books published.
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Sciences Foundation of China, No.39270786.
Correspondence to: Dr. Zhi-Rong Zhang, School of Pharmacy, West China University of Medical Sciences, Chengdu, 610041, China.
Telephone: +86-28-5501566 Fax:+86-28-5583252
Received: August 10, 1999
Revised: September 12, 1999
Accepted: September 29, 1999
Published online: December 15, 1999
Abstract

AIM: To study the anticarcinogenic effect and acute toxicity of liver targeting mitoxantrone-nanospheres.

METHODS: The anticarcinogenic effect of mitoxantrone-polybutyl cyanoacrylate-nanoparticles ( DHAQ-PBCA-NP ) was investigated by using heterotopic and orthotopic transplantation models of human hepatocellular carcinoma ( HCC ) in nude mice and was compared with mitoxantrone (DHAQ) and doxorubicin (ADR). The acute toxicity of DHAQ-PBCA-NP lyophilized injection in mice was also studied.

RESULTS: The tumor inhibition rates of ADR, DHAQ, DHAQ-PBCA-NP to orthotopically transplanted HCC were 60.07%, 67.49% and 99.44%, respectively, but regard to heterotopically transplanted HCC, these were 80.03%, 86.18% and 92.90%, which were concordant with the results acquired by mitosis counting and proliferating cell nuclear antigen (PCNA). After iv administration to mice with DHAQ-PBCA-NP, the LD50 was 16.9 mg/kg ± 3.9 mg/kg, no obvious local irritation was observed and there was no significant damage to the structure of liver cells, and that of the heart, spleen and kidneys.

CONCLUSION: The effect of DHAQ-PBCA-NP was significantly higher than that of DHAQ and ADR in the anti-orthotopically transplanted HCC and the acute toxicity was relatively low.

Keywords: mitoxantrone-nanospheres toxicity; neoplasm transplantation; nude mice