A Novel Monomethoxy Polyethylene Glycol–Polylactic Acid Polymeric Micelles with Higher Loading Capacity for Docetaxel and Well-Reconstitution Characteristics and Its Anti-metastasis Study
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- Li Yunfei
- State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Chinese Academy of Medical Sciences
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- Yang Feifei
- State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Chinese Academy of Medical Sciences
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- Chen Wei
- State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Chinese Academy of Medical Sciences
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- Liu Jiaoyang
- Pharmacy School, Yanbian University
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- Huang Wei
- State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Chinese Academy of Medical Sciences
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- Jin Mingji
- State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Chinese Academy of Medical Sciences
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- Gao Zhonggao
- State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Chinese Academy of Medical Sciences Department of Bioengineering, University of Utah
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抄録
Docetaxel (DTX) is hydrophobic, and its available formulations (Taxotere® & Duopafei®) require Tween80 and ethanol vehicle to allow parental administration. DTX-loaded poly(D,L-lactide)-b-polyethylene glycol–methoxy (mPEG-b-PDLLA) polymeric micelle (PM) is a Tween80-free formulation of DTX, which has been extensively studied but rarely involved with industrialization issues. In this work, novel DTX-PM with improved loading capacity and well-reconsitution ability was developed. The freeze-dried DTX-PM was analyzed by HPLC, transmission electron microscopy (TEM) and dynamic light scattering (DLS) to determine the DTX loading, micelle morphology and size respectively. The in vitro cytotoxic activity of DTX-PM in 4T1 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the corresponding in vivo study was assessed in BALB/c mice bearing 4T1 tumor through intravenous administration. The DTX-loading and efficiency into the micelles were 20.74±1.23% and 93.7±1.03% respectively, which was much higher than ever reported PM. The DTX-PM was spherical with a mean particle size of 16.62±0.31 nm, which suggested that they were able to selectively accumulate in solid tumors by enhanced permeability and retention (EPR) effect. Another important characteristic of DTX-PM is the long term storage and reuses as aqueous injection solution. Many kinds of lyoprotectants were also investigated and dextrose was found to an excellent one. Compared with Duopafei®, DTX-PM showed better cytotoxicity and anti-metastasis ability against 4T1 cells in vitro and in vivo. In conclusion, DTX-PM significantly enhanced drug-loading capacity of DTX and had well-reconsitution ability, which could be a promising drug delivery system for clinic.
収録刊行物
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- CHEMICAL & PHARMACEUTICAL BULLETIN
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CHEMICAL & PHARMACEUTICAL BULLETIN 60 (9), 1146-1154, 2012
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679155852800
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- NII論文ID
- 130001852534
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- NII書誌ID
- AA00602100
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- COI
- 1:STN:280:DC%2BC38bmvVSnug%3D%3D
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- ISSN
- 13475223
- 00092363
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- NDL書誌ID
- 023900138
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- PubMed
- 22976323
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可