TY - JOUR
T1 - A PEG-Fmoc conjugate as a nanocarrier for paclitaxel
AU - Zhang, Peng
AU - Huang, Yixian
AU - Liu, Hao
AU - Marquez, Rebecca T.
AU - Lu, Jianqin
AU - Zhao, Wenchen
AU - Zhang, Xiaolan
AU - Gao, Xiang
AU - Li, Jiang
AU - Venkataramanan, Raman
AU - Xu, Liang
AU - Li, Song
N1 - Funding Information:
This work was supported in part by NIH grants R21CA173887 , RO1CA174305 , and R01GM102989 . We would like to thank Dr. Lisa Rohan for her help in DSC study.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - 9-Fluorenylmethoxycarbonyl
KW - Cancer therapy
KW - Drug delivery
KW - Drug-carrier interaction
KW - Micelle
KW - Paclitaxel
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U2 - 10.1016/j.biomaterials.2014.04.108
DO - 10.1016/j.biomaterials.2014.04.108
M3 - Article
C2 - 24856103
AN - SCOPUS:84902078210
SN - 0142-9612
VL - 35
SP - 7146
EP - 7156
JO - Biomaterials
JF - Biomaterials
IS - 25
ER -