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,Kathy Qian Luo,Alex Chang,Xiaofeng Liu

doi:10.18632/oncotarget.14481

Qi Wang, Na Wei + Show 3 more

Open Access

https://doi.org/10.18632/oncotarget.14481

Copy DOI

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 (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.

Highlights

Worldwide, breast cancer is the predominant cause of female mortality
Fourier transform infrared (FT-IR) spectra further confirmed the successful synthesis of the compound acetyltanshinone IIA (ATA)
A characteristic band of Tanshinone IIA (TIIA) was detected at 2951.09 cm−1, which was assigned to the C-H vibration

Summary

Introduction

Among all types of breast cancers, approximately 65% express high levels of the estrogen receptor (ER) [1,2,3]. The most effective drug to treat ER+ breast cancer are tamoxifen and fulvestrant. Tanshinone IIA (TIIA), a lipophilic pharmacologically active compound extracted from the medicinal herbal plant Radix Salviae miltiorrhizae (Danshen), has been widely used to treat cardiovascular diseases [18,19,20]. Recent pharmacological studies have revealed the anti-cancer effect of TIIA on various types of cancer cells [21,22]. We found that a chemically modified compound of TIIA, acetyltanshinone IIA (ATA), had the potential to be a more effective anti-ER+ breast cancer agent than the current therapeutics [23]

Methods

Results

Conclusion