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Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: Preparation and comparison with other paclitaxel systems in vitro and in vivo
Lu, Jingkai1; Chuan, Xingxing1; Zhang, Hua1; Dai, Wenbing1; Wang, Xinglin2; Wang, Xueqing1; Zhang, Qiang1
关键词Paclitaxel Pegylated Paclitaxel Peg-pla Taxol Nanoparticles Antitumor Effect
刊名INTERNATIONAL JOURNAL OF PHARMACEUTICS
2014-08-25
DOI10.1016/j.ijpharm.2014.05.032
471期:1-2页:525-535
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]POLYMERIC MICELLE FORMULATION ; DRUG-DELIVERY SYSTEMS ; PHASE-II TRIAL ; CREMOPHOR-FREE ; GENEXOL-PM ; LUNG-CANCER ; EFFICACY ; PRODRUGS ; SOLUBILITY ; CONJUGATE
英文摘要

Previously, PEGylated paclitaxel (PEG-PTX) was found not favorable as a polymer prodrug because of its poor antitumor efficiency. But surprisingly, it was found in our study that PEG-PTX could form a novel nanoparticle system with free PTX. To address how this system works, we compared PTX loaded PEG-PTX nanoparticles (PEG-PTX/PTX) with PTX loaded PEG-PLA micelles (PEG-PLA/PTX) or PTX injection available (Taxol((R))) in vitro and in vivo. Firstly, it was found that PEG-PTX/PTX was more stable in aqueous solution than PEG-PLA/PTX in terms of PTX crystal formation and drug release. Then it was demonstrated that coumarin loaded PEG-PTX nanoparticles had a much higher uptake in MCF-7 cells compared to coumarin loaded PEG-PLA micelles. The in vivo imaging study revealed that DIR or DID (near infrared fluorescent substances) loaded PEG-PTX nanoparticles distributed more in tumors in MCF-7 tumor bearing mice than DIR or DID loaded PEG-PLA micelles and solvent system of Taxol((R)). In the efficacy study with MCF-7 tumor bearing mice, PEG-PTX/PTX showed significantly higher antitumor activity than PEG-PLA/PTX at the same PTX dosage. At the dose of 10 mg free PTX per kg, PEG-PTX/PTX displayed similar efficacy as Taxol((R)) but less toxicity evaluated by the loss of body weight. With the increase of free PTX to 15 mg/kg, PEG-PTX/PTX showed significantly better efficacy than Taxol((R)). In conclusion, with favorable characteristics in stability, cellular uptake, cytotoxicity, biodistribution, safety and efficacy, PEG-PTX/PTX seems highly potential as a nanocarrier for PTX delivery. (C) 2014 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000338423600059
项目编号81130059 ; 81273456 ; 2012CB724002
资助机构National Natural Science Foundation of China ; National Basic Research Program of China
引用统计
被引频次:37[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56392
专题北京大学药学院
北京大学药学院_药剂学系
作者单位1.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Tianjin Inst Pharmaceut Res, State Key Lab Drug Delivery Technol & Pharmacokin, Tianjin 300193, Peoples R China
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GB/T 7714
Lu, Jingkai,Chuan, Xingxing,Zhang, Hua,et al. Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: Preparation and comparison with other paclitaxel systems in vitro and in vivo[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2014,471(1-2):525-535.
APA Lu, Jingkai.,Chuan, Xingxing.,Zhang, Hua.,Dai, Wenbing.,Wang, Xinglin.,...&Zhang, Qiang.(2014).Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: Preparation and comparison with other paclitaxel systems in vitro and in vivo.INTERNATIONAL JOURNAL OF PHARMACEUTICS,471(1-2),525-535.
MLA Lu, Jingkai,et al."Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: Preparation and comparison with other paclitaxel systems in vitro and in vivo".INTERNATIONAL JOURNAL OF PHARMACEUTICS 471.1-2(2014):525-535.
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