A novel self‐assembly albumin nanocarrier for reducing doxorubicin‐mediated cardiotoxicity. Issue 5 (19th February 2013)

• Record Type: Journal Article
• Authors: Yuan, Ahu; Wu, Jinhui; Song, Chenchen; Tang, Xiaolei; Qiao, Qian; Zhao, Lili; Gong, Guangming; Hu, Yiqiao
• Is Part Of: Journal of pharmaceutical sciences. Volume 102:Issue 5(2013:May)
• Page Start: 1626
• Page End: 1635
• Publication Date: 2013-02-19
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23455
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Doxorubicin is an antitumor drug commonly used against a wide spectrum of tumors. However, the clinical application of DOX is restricted by its cardiotoxicity. To reduce the cardiotoxicity, we develop an albumin‐based nanocarrier via a new molecular switch method for DOX delivery. Spherically shaped DOX‐loaded HSA nanoparticles (NPs‐DOX) are prepared with a drug‐loading capacity and particle size of 4.3% and 120.1 ± 26 nm, respectively. <italic>In vivo</italic> studies demonstrate that NPs‐DOX is able to preferentially accumulate in tumor and show great tumor inhibition on H22 hepatocellular‐carcinoma‐bearing mice. As for the toxicity, compared with free DOX, the maximum tolerated dose of NPs‐DOX is increased from 10 to over 30 mg/kg, indicating the reduced systematic toxicity. More importantly, the cardiotoxicity induced by NPs‐DOX is also significantly reduced because both left ventricular ejection fraction and left ventricular fractional shortening are almost not changed and other cardiotoxicity markers such as serum creatine kinase‐MB, lactate dehydrogenase, superoxide dismutase, and malonaldehyde are kept constant. The reduced cardiotoxicity of NPs‐DOX is also confirmed by nonhistological changes in the heart tissue. Therefore, such albumin‐based nanocarrier can be one of the most promising strategies for the delivery of DOX. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1626–1635, 2013</p> </abstract>