A PEG-Fmoc conjugate as a nanocarrier for paclitaxel

Peng Zhang, Yixian Huang, Hao Liu, Rebecca T. Marquez, Jianqin Lu, Wenchen Zhao, Xiaolan Zhang, Xiang Gao, Jiang Li, Raman Venkataramanan, Liang Xu, Song Li

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

We report here that a simple, well-defined, and easy-to-scale up nanocarrier, PEG5000-lysyl-(α-Fmoc-ε-t-Boc-lysine)2 conjugate (PEG-Fmoc), provides high loading capacity, excellent formulation stability and low systemic toxicity for paclitaxel (PTX), a first-line chemotherapeutic agent for various types of cancers. 9-Fluorenylmethoxycarbonyl (Fmoc) was incorporated into the nanocarrier as a functional building block to interact with drug molecules. PEG-Fmoc was synthesized via a three-step synthetic route, and it readily interacted with PTX to form mixed nanomicelles of small particle size (25-30nm). The PTX loading capacity was about 36%, which stands well among the reported micellar systems. PTX entrapment in this micellar system is achieved largely via an Fmoc/PTX π-π stacking interaction, which was demonstrated by fluorescence quenching studies and 13C NMR. PTX formulated in PEG-Fmoc micelles demonstrated sustained release kinetics, and invivo distribution study via near infrared fluorescence imaging demonstrated an effective delivery of Cy5.5-labled PTX to tumor sites. The maximal tolerated dose for PTX/PEG-Fmoc (MTD>120mg PTX/kg) is higher than those for most reported PTX formulations, and invivo therapeutic study exhibited a significantly improved antitumor activity than Taxol, a clinically used formulation of PTX. Our system may hold promise as a simple, safe, and effective delivery system for PTX with a potential for rapid translation into clinical study.

Original languageEnglish (US)
Pages (from-to)7146-7156
Number of pages11
JournalBiomaterials
Volume35
Issue number25
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • 9-Fluorenylmethoxycarbonyl
  • Cancer therapy
  • Drug delivery
  • Drug-carrier interaction
  • Micelle
  • Paclitaxel

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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