TY - JOUR
T1 - Oral nano-delivery of anticancer ginsenoside 25-OCH3-PPD, a natural inhibitor of the MDM2 oncogene
T2 - Nanoparticle preparation, characterization, in vitro and in vivo anti-prostate cancer activity, and mechanisms of action
AU - Voruganti, Sukesh
AU - Qin, Jiang Jiang
AU - Sarkar, Sushanta
AU - Nag, Subhasree
AU - Walbi, Ismail A.
AU - Wang, Shu
AU - Zhao, Yuqing
AU - Wang, Wei
AU - Zhang, Ruiwen
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Ginsenoside
KW - MDM2
KW - Molecular targeting efficiency
KW - Oral delivery
KW - PEG-PLGA nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=84940755759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940755759&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.4091
DO - 10.18632/oncotarget.4091
M3 - Article
C2 - 26041888
AN - SCOPUS:84940755759
SN - 1949-2553
VL - 6
SP - 21379
EP - 21394
JO - Oncotarget
JF - Oncotarget
IS - 25
ER -