Journal of Chinese Pharmaceutical Sciences ›› 2018, Vol. 27 ›› Issue (8): 530-539.DOI: 10.5246/jcps.2018.08.054

• Original articles • Previous Articles     Next Articles

Preparation and characterization of dual pH-sensitive polymer-doxorubicin conjugate micelles

Yang Zou, Yao Jin, Yuanhang Zhou, Chuyu He, Yunqiang Deng, Shidi Han, Chuhang Zhou, Xinru Li, Yanxia Zhou, Yan Liu*   

  1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2018-04-21 Revised:2018-06-16 Online:2018-09-04 Published:2018-07-05
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  • Supported by:

    National Natural Science Foundation of China (Grant No. 81673366) and the National Key Science Research Program of China (973 Program, Grant No. 2015CB932100).


In the present study, we designed and fabricated pH-sensitive polymeric micelles based on the conjugate of poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) with doxorubicin (PEOz-PLA-imi-DOX) to efficiently inhibit tumor cell growth. Hence, PEOz-PLA-imi-DOX was successfully synthesized by connecting DOX to the hydrophobic end of pH-sensitive PEOz-PLAvia acid cleavable benzoic imine linker and characterized by 1H NMR spectrum and thin layer chromatography. The critical micelle concentration of PEOz-PLA-imi-DOX was determined to be (14.84±3.85) mg/L. The conjugate micelles (denoted as PP-DOX-PM) formed by PEOz-PLA-imi-DOX using film-hydration method were characterized to have a nano-scaled size of about 21 nm in diameter, and the drug loading content was 1.67%. PP-DOX-PM showed pH-dependent drug release behavior with gradually accelerated release of DOX with decrease of pH value, illustrating the micelles’ distinguishing feature of endo/lysosomal pH from physiological pH by accelerating drug release. As anticipated, PP-DOX-PM maintained the cytotoxicity of DOX against MDA-MB-231 cells. Collectively, PP-DOX-PM might have great potential for effective suppression of tumor growth. 

Key words: Doxorubicin, Acid-cleavable imine, Polymer-drug conjugate, pH-sensitive polymeric micelles, In vitro release

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