A PEG-Fmoc conjugate as a nanocarrier for paclitaxel.

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 (13)C 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.

• Authors: 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
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 25 Pg. 7146-56 (Aug 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 24856103 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Drug Carriers
• Micelles
• Polymers
• Paclitaxel

Topics

• Animals
• Cell Line, Tumor
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Female
• Humans
• Male
• Maximum Tolerated Dose
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Micelles
• Nanoparticles (chemistry)
• Paclitaxel (chemistry)
• Polymers (chemistry)