Xiaowei Dong

University of North Texas Health Science Center, USA

Title: Toxicity study of oral docetaxel nanoformulation

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Biography

Xiaowei Dong has completed his PhD in Pharmaceutical Sciences from University of Kentucky and then joined Novartis Pharmaceutical Corporation working as a lead formulator for drug product development for about 4 years. In 2013, she joined UNT Health Science Center as an assistant professor in the Department of Pharmaceutical Sciences at the College of Pharmacy. Her research includes drug delivery and formulation development using nanotechnology and has special focus on novel oral formulation technology.

Abstract

Although oral delivery is the most favorable and preferred route of drug administration, many chemotherapy drugs (e.g. docetaxel) have been commercially formulated for intravenous injections because of low oral absorption. Metronomic chemotherapy, giving low doses of chemotherapy drugs on a frequent schedule over a long time, may improve outcomes and reduce side effects for cancer patients. Oral drug formulations are essential for metronomic chemotherapy. However, the toxicity of orally administrated anticancer drugs was not widely studies. In this study, the toxicity of an oral docetaxel nanoformulation was evaluated to establish the maximum tolerated dose (MTD) and identify the tissue which was affected. Docetaxel is a poorly water-soluble drug with low permeability. Thus, it is very challenging to develop oral docetaxel formulation with sufficient absorption. Recently, our lab has developed a new docetaxel granule that does not have nanoparticles, but upon contact with water the granule generated docetaxel-entrapped in situ self-assembly nanoparticles. FVB mice were administered with docetaxel granule by oral gavage once per day. A dose range from 10 -400 mg/kg of docetaxel granule was tested. Alanine Transaminase activity was measured to evaluate liver function, and blood urea nitrogen was measured for renal function. Finally, kidney, liver and lung were stained with H&E and imaged by a microscopy. The results demonstrated that the MTD of docetaxel granule was 25 mg/kg for once daily. High dose docetaxel granule reduced renal function but not liver function, which was further confirmed by histology analysis.