PEG-derivatized embelin as a dual functional carrier for the delivery of paclitaxel

Yixian Huang, Jianqin Lu, Xiang Gao, Jiang Li, Wenchen Zhao, Ming Sun, Donna Beer Stolz, Raman Venkataramanan, Lisa Cencia Rohan, Song Li

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1443-1451
Number of pages9
JournalBioconjugate Chemistry
Volume23
Issue number7
DOIs
StatePublished - Jul 18 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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