Oncotarget

Research Papers:

Oral nano-delivery of anticancer ginsenoside 25-OCH3-PPD, a natural inhibitor of the MDM2 oncogene: Nanoparticle preparation, characterization, in vitro and in vivo anti-prostate cancer activity, and mechanisms of action

Sukesh Voruganti _, Jiang-Jiang Qin, Sushanta Sarkar, Subhasree Nag, Ismail A. Walbi, Shu Wang, Yuqing Zhao, Wei Wang and Ruiwen Zhang

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Oncotarget. 2015; 6:21379-21394. https://doi.org/10.18632/oncotarget.4091

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Abstract

Sukesh Voruganti1,*, Jiang-Jiang Qin1,*, Sushanta Sarkar1, Subhasree Nag1, Ismail A. Walbi1, Shu Wang3, Yuqing Zhao4, Wei Wang1,2, Ruiwen Zhang1,2

1Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA

2Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA

3Nutritional Science Program, Texas Tech University, Lubbock, TX 79409, USA

4School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China

*These authors have contributed equally to this work

Correspondence to:

Ruiwen Zhang, e-mail: ruiwen.zhang@ttuhsc.edu

Wei Wang, e-mail: wwei.wang@ttuhsc.edu

Keywords: molecular targeting efficiency, MDM2, ginsenoside, PEG-PLGA nanoparticles, oral delivery

Received: March 16, 2015     Accepted: May 12, 2015     Published: May 24, 2015

ABSTRACT

The Mouse Double Minute 2 (MDM2) oncogene plays a critical role in cancer development and progression through p53-dependent and p53-independent mechanisms. Both natural and synthetic MDM2 inhibitors have been shown anticancer activity against several human cancers. We have recently identified a novel ginsenoside, 25-OCH3-PPD (GS25), one of the most active anticancer ginsenosides discovered thus far, and have demonstrated its MDM2 inhibition and anticancer activity in various human cancer models, including prostate cancer. However, the oral bioavailability of GS25 is limited, which hampers its further development as an oral anticancer agent. The present study was designed to develop a novel nanoparticle formulation for oral delivery of GS25. After GS25 was successfully encapsulated into PEG-PLGA nanoparticles (GS25NP) and its physicochemical properties were characterized, the efficiency of MDM2 targeting, anticancer efficacy, pharmacokinetics, and safety were evaluated in in vitro and in vivo models of human prostate cancer. Our results indicated that, compared with the unencapsulated GS25, GS25NP demonstrated better MDM2 inhibition, improved oral bioavailability and enhanced in vitro and in vivo activities. In conclusion, the validated nano-formulation for GS25 oral delivery improves its molecular targeting, oral bioavailability and anticancer efficacy, providing a basis for further development of GS25 as a novel agent for cancer therapy and prevention.


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