TY - JOUR
T1 - PEG-derivatized embelin as a dual functional carrier for the delivery of paclitaxel
AU - Huang, Yixian
AU - Lu, Jianqin
AU - Gao, Xiang
AU - Li, Jiang
AU - Zhao, Wenchen
AU - Sun, Ming
AU - Stolz, Donna Beer
AU - Venkataramanan, Raman
AU - Rohan, Lisa Cencia
AU - Li, Song
PY - 2012/7/18
Y1 - 2012/7/18
N2 - Embelin, identified primarily from the Embelia ribes plant, has been shown to be a natural small molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP). It is also a potent inhibitor of NF-κB activation, which makes it a potentially effective suppressor of tumor cell survival, proliferation, invasion, angiogenesis, and inflammation. However, embelin itself is insoluble in water, which makes it unsuitable for in vivo applications. In this work, we developed a novel micelle system through conjugating embelin to a hydrophilic polymer, poly(ethylene glycol) 3500 (PEG3.5K) through an aspartic acid bridge. The PEG3.5k-embelin2 (PEG 3.5k-EB2) conjugate readily forms micelles in aqueous solutions with a CMC of 0.0205 mg/mL. Furthermore, PEG3.5k-EB 2 micelles effectively solubilize paclitaxel (PTX), a model hydrophobic drug used in this study. Both drug-free and drug-loaded micelles were small in size (20-30 nm) with low polydispersity indexes. In vitro cytotoxicity studies with several tumor cell lines showed that PEG 3.5k-EB2 is comparable to embelin in antitumor activity and synergizes with PTX at much lower doses. Our results suggest that PEG-derivatized embelin may represent a novel and dual-functional carrier to facilitate the in vivo applications of poorly water-soluble anticancer drugs such as PTX.
AB - Embelin, identified primarily from the Embelia ribes plant, has been shown to be a natural small molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP). It is also a potent inhibitor of NF-κB activation, which makes it a potentially effective suppressor of tumor cell survival, proliferation, invasion, angiogenesis, and inflammation. However, embelin itself is insoluble in water, which makes it unsuitable for in vivo applications. In this work, we developed a novel micelle system through conjugating embelin to a hydrophilic polymer, poly(ethylene glycol) 3500 (PEG3.5K) through an aspartic acid bridge. The PEG3.5k-embelin2 (PEG 3.5k-EB2) conjugate readily forms micelles in aqueous solutions with a CMC of 0.0205 mg/mL. Furthermore, PEG3.5k-EB 2 micelles effectively solubilize paclitaxel (PTX), a model hydrophobic drug used in this study. Both drug-free and drug-loaded micelles were small in size (20-30 nm) with low polydispersity indexes. In vitro cytotoxicity studies with several tumor cell lines showed that PEG 3.5k-EB2 is comparable to embelin in antitumor activity and synergizes with PTX at much lower doses. Our results suggest that PEG-derivatized embelin may represent a novel and dual-functional carrier to facilitate the in vivo applications of poorly water-soluble anticancer drugs such as PTX.
UR - http://www.scopus.com/inward/record.url?scp=84863938550&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863938550&partnerID=8YFLogxK
U2 - 10.1021/bc3000468
DO - 10.1021/bc3000468
M3 - Article
C2 - 22681537
AN - SCOPUS:84863938550
VL - 23
SP - 1443
EP - 1451
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 7
ER -