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Thermosensitive mPEG-b-PA-g-PNIPAM Comb Block Copolymer Micelles: Effect of Hydrophilic Chain Length and Camptothecin Release Behavior

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ABSTRACT

Purpose

Block copolymer micelles are extensively used as drug controlled release carriers, showing promising application prospects. The comb or brush copolymers are especially of great interest, whose densely-grafted side chains may be important for tuning the physicochemical properties and conformation in selective solvents, even in vitro drug release. The purpose of this work was to synthesize novel block copolymer combs via atom transfer radical polymerization, to evaluate its physicochemical features in solution, to improve drug release behavior and to enhance the bioavailablity, and to decrease cytotoxicity.

Methods

The physicochemical properties of the copolymer micelles were examined by modulating the composition and the molecular weights of the building blocks. A dialysis method was used to load hydrophobic camptothecin (CPT), and the CPT release and stability were detected by UV–vis spectroscopy and high-performance liquid chromatography, and the cytotoxicity was evaluated by MTT assays.

Results

The copolymers could self-assemble into well-defined spherical core-shell micelle aggregates in aqueous solution, and showed thermo-induced micellization behavior, and the critical micelle concentration was 2.96–27.64 mg L−1. The micelles were narrow-size-distribution, with hydrodynamic diameters about 128–193 nm, depending on the chain length of methoxy polyethylene glycol (mPEG) blocks and poly(N-isopropylacrylamide) (PNIPAM) graft chains or/and compositional ratios of mPEG to PNIPAM. The copolymer micelles could stably and effectively load CPT but avoid toxicity and side-effects, and exhibited thermo-dependent controlled and targeted drug release behavior.

Conclusions

The copolymer micelles were safe, stable and effective, and could potentially be employed as CPT controlled release carriers.

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Acknowledgments and Disclosures

This work is supported by the Natural Science Foundation of China (grant NSFC 21273142), Natural Science Foundation of Shaanxi Province (2012JM6009), and Graduate Education Innovation Funds (2013CXS049).

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Authors and Affiliations

  1. Key Laboratory of Macromolecular Science of Shaanxi Province School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an, 710062, People’s Republic of China

    Xiao-Li Yang, Yan-Ling Luo, Feng Xu & Ya-Shao Chen

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  1. Xiao-Li Yang
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  2. Yan-Ling Luo
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Correspondence to Yan-Ling Luo or Feng Xu.

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Yang, XL., Luo, YL., Xu, F. et al. Thermosensitive mPEG-b-PA-g-PNIPAM Comb Block Copolymer Micelles: Effect of Hydrophilic Chain Length and Camptothecin Release Behavior. Pharm Res 31, 291–304 (2014). https://doi.org/10.1007/s11095-013-1160-y

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  • DOI: https://doi.org/10.1007/s11095-013-1160-y

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