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

doi:10.5246/jcps.2018.08.054

Abstract

Abstract:

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

CLC Number:

R944

Supporting:

Yang Zou, Yao Jin, Yuanhang Zhou, Chuyu He, Yunqiang Deng, Shidi Han, Chuhang Zhou, Xinru Li, Yanxia Zhou, Yan Liu. Preparation and characterization of dual pH-sensitive polymer-doxorubicin conjugate micelles[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(8): 530-539.

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