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Pharmacokinetics in Rats and Efficacy in Murine Ovarian Cancer Model for Solid Lipid Nanoparticles Loading Docetaxel

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Abstract:

Docetaxel was used extensively in ovarian cancer treatment in the combination with platinum compound. However, the serious side effect of clinically available formulation limits its further application. The aim of this work was to evaluate the pharmacokinetic behavior, acute toxicity and in vivo antitumor efficacy in murine ovarian cancer model of docetaxel loaded solid lipid nanoparticles (DSN). The particle size of DSN was 97.4±6.4 nm, and the encapsulation efficiency and loading capacity were 91.1±1.5% and 3.52±0.05%, respectively. The release behavior of docetaxel from DSN showed that only 45% of docetaxel was released within 24 h. The pharmacokinetics and biodistribution showed that the half-life (t1/2) and mean residence time (MRT) of docetaxel in DSN treated rats were significantly elongated because of the redistribution of docetaxel from reticulo-endothelial system (RES) to circulation system. Compared with Taxotere®, DSN showed more potent in vivo anti-ovarian cancer activity with higher maximum tolerated dose (MTD). Our results suggested for the first time that solid lipid nanoparticles could be a potential candidate to enhance the efficacy of anti-ovarian cancer of docetaxel with low toxicity. The systematical study on pharmacokinetics, biodistribution, in vivo anti-tumor activity and MTD of DSN could improve the understanding of increased antitumor activity of DSN in vivo.

Keywords: ANTI-TUMOR EFFICACY; DOCETAXEL; OVARIAN CARCINOMA; PHARMACOKINETICS; SOLID LIPID NANOPARTICLES

Document Type: Research Article

DOI: http://dx.doi.org/10.1166/jnn.2010.2819

Publication date: November 1, 2010

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  • Journal for Nanoscience and Nanotechnology (JNN) is an international and multidisciplinary peer-reviewed journal with a wide-ranging coverage, consolidating research activities in all areas of nanoscience and nanotechnology into a single and unique reference source. JNN is the first cross-disciplinary journal to publish original full research articles, rapid communications of important new scientific and technological findings, timely state-of-the-art reviews with author's photo and short biography, and current research news encompassing the fundamental and applied research in all disciplines of science, engineering and medicine.
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