The AAPS Journal

, Volume 16, Issue 1, pp 114–124 | Cite as

Design and Evaluation of a PEGylated Lipopeptide Equipped with Drug-Interactive Motifs as an Improved Drug Carrier

  • Peng Zhang
  • Jianqin Lu
  • Yixian Huang
  • Wenchen Zhao
  • Yifei Zhang
  • Xiaolan Zhang
  • Jiang Li
  • Raman Venkataramanan
  • Xiang GaoEmail author
  • Song LiEmail author
Research Article


Micelles are attractive delivery systems for hydrophobic drugs due to their small size and the ease of application. However, the limited drug loading capacity and the intrinsic poor stability of drug-loaded formulations represent two major issues for some micellar systems. In this study, we designed and synthesized a micelle-forming PEG-lipopeptide conjugate with two Fmoc groups located at the interfacial region, and two oleoyl chains as the hydrophobic core. The significance of Fmoc groups as a broadly applicable drug-interactive motif that enhances the carrier–drug interaction was examined using eight model drugs of diverse structures. Compared with an analogue without carrying a Fmoc motif, PEG5000-(Fmoc-OA)2 demonstrated a lower value of critical micelle concentration and three-fold increases of loading capacity for paclitaxel (PTX). These micelles showed tubular structures and small particle sizes (∼70 nm), which can be lyophilized and readily reconstituted with water without significant changes in particle sizes. Fluorescence quenching study illustrated the Fmoc/PTX π–π stacking contributes to the carrier/PTX interaction, and drug-release study demonstrated a much slower kinetics than Taxol, a clinically used PTX formulation. PTX/PEG5000-(Fmoc-OA)2 mixed micelles exhibited higher levels of cytotoxicity than Taxol in several cancer cell lines and more potent inhibitory effects on tumor growth than Taxol in a syngeneic murine breast cancer model (4T1.2). We have further shown that seven other drugs can be effectively formulated in PEG5000-(Fmoc-OA)2 micelles. Our study suggests that micelle-forming PEG-lipopeptide surfactants with interfacial Fmoc motifs may represent a promising formulation platform for a broad range of drugs with diverse structures.


drug-interactive motif micelle paclitaxel slow release 



This work was supported in part by NIH grants (R01GM102989, R21CA173887, and R21CA155983) and a DOD grant (BC09603).

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Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Peng Zhang
    • 1
    • 2
    • 3
  • Jianqin Lu
    • 1
    • 2
    • 3
  • Yixian Huang
    • 1
    • 2
    • 3
  • Wenchen Zhao
    • 2
  • Yifei Zhang
    • 1
    • 2
    • 3
  • Xiaolan Zhang
    • 1
    • 2
    • 3
  • Jiang Li
    • 1
    • 2
    • 3
  • Raman Venkataramanan
    • 2
  • Xiang Gao
    • 1
    • 2
    • 3
    Email author
  • Song Li
    • 1
    • 2
    • 3
    Email author
  1. 1.Center for Pharmacogenetics, School of PharmacyUniversity of PittsburghPittsburghUSA
  2. 2.Department of Pharmaceutical Sciences, School of PharmacyUniversity of PittsburghPittsburghUSA
  3. 3.University of Pittsburgh Cancer InstituteUniversity of PittsburghPittsburghUSA

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