Enhancement of the bioavailability of a novel anticancer compound (acetyltanshinone IIA) by encapsulation within mPEG-PLGA nanoparticles: A study of formulation optimization, toxicity, and pharmacokinetics
Luo, Kathy Qian
Date of Issue2017
School of Chemical and Biomedical Engineering
The Poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (mPEG-PLGA) nanoparticles carrying acetyltanshinone IIA (ATA), a novel anti-breast cancer agent, were prepared by ultrasonic emulsion method to enhance the bioavailability and reduce the toxicity. Systematic optimization of encapsulation process was achieved using an orthogonal design. Drug efficacy analysis showed that ATA nanoparticles were as effective as free ATA against estrogen receptor positive breast cancer cells, but much less toxic towards human endothelial cells. Furthermore, in zebrafish, ATA nanoparticles displayed much lower toxicity than free ATA. More importantly, the blood concentration of ATA nanoparticles indicated by 24 hour-area under the curve (AUC0-24h) was 10 times higher than free ATA. These results indicated the potential of ATA-loaded mPEG-PLGA nanoparticles for the delivery of ATA in a clinical formulation, and their potential for use in tumor therapy in the future.
© 2017 The Author(s) (published by Impact Journals). This paper is licensed under a Creative Commons Attribution 3.0 License. This paper was published in Oncotarget and is made available as an electronic reprint (preprint) with permission of The Author(s) (published by Impact Journals). The published version is available at: [http://dx.doi.org/10.18632/oncotarget.14481]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.