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A PEG-Fmoc conjugate as a nanocarrier for paclitaxel

Zhang, Peng
Huang, Yixian
Liu, Hao
Marquez, Rebecca T.
Lu, Jianqin
Zhao, Wenchen
Zhang, Xiaolan
Gao, Xiang
Li, Jiang
Venkataramanan, Raman
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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 (25–30 nm). 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 in vivo 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 > 120 mg PTX/kg) is higher than those for most reported PTX formulations, and in vivo 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.
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Date
2014-08
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Publisher
Elsevier
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Keywords
Micelle, 9-Fluorenylmethoxycarbonyl, Drug-carrier interaction, Drug delivery, Paclitaxel, Cancer therapy
Citation
Zhang, P., Huang, Y., Liu, H., Marquez, R., Lu, J., Zhao, W., … Li, S. (2014). A PEG-Fmoc conjugate as a nanocarrier for paclitaxel. Biomaterials, 35(25), 7146–7156. http://doi.org/10.1016/j.biomaterials.2014.04.108
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