A PEG-Fmoc conjugate as a nanocarrier for paclitaxel

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• 作者：Peng Zhang^a ; ^b ; ^c ; Yixian Huang^a ; ^b ; ^c ; Hao Liu^d ; ^e ; Rebecca T. Marquez^d ; ^e ; Jianqin Lu^a ; ^b ; ^c ; Wenchen Zhao^b ; Xiaolan Zhang^a ; ^b ; ^c ; Xiang Gao^a ; ^b ; ^c ; Jiang Li^a ; ^b ; ^c ; Raman Venkataramanan^b ; Liang Xu^d ; ^e ; Song Li^a ; ^b ; ^c ; ^{sol4@pitt.edu" class="auth_mail}
• 关键词：Micelle ; 9-Fluorenylmethoxycarbonyl ; Drug&ndash ; carrier interaction ; Paclitaxel ; Drug delivery ; Cancer therapy
• 刊名：Biomaterials
• 出版年：August 2014
• 年：2014
• 卷：35
• 期：25
• 页码：7146-7156
• 全文大小：3428 K

文摘

We report here that a simple, well-defined, and easy-to-scale up nanocarrier, PEG₅₀₀₀-lysyl-(伪-Fmoc-蔚-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 蟺–蟺 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.