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

Qi Wang; Na Wei; Xiaofeng Liu; Kathy Qian Luo

doi:10.18632/oncotarget.14481

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Research Papers:

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

Qi Wang, Na Wei, Xiaofeng Liu and Kathy Qian Luo _

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Oncotarget. 2017; 8:12013-12030. https://doi.org/10.18632/oncotarget.14481

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Abstract

Qi Wang1, Na Wei1, Xiaofeng Liu1, Alex Chang2, Kathy Qian Luo3

1School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore

2Department of Oncology, Johns Hopkins Singapore, Singapore

3Faculty of Health Sciences, University of Macau, Taipa, Macau, China

Correspondence to:

Kathy Qian Luo, email: [email protected]

Keywords: anticancer drugs, acetyltanshinone IIA, bioavailability, mPEG-PLGA, toxicity, pharmacokinetics

Received: November 30, 2016 Accepted: December 16, 2016 Published: January 04, 2017

ABSTRACT

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 (AUC_0-24h) 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.

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Research Papers:

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

Abstract