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pH-sensitive micelles self-assembled from polymer brush (PAE-g-cholesterol)-b-PEG-b-(PAE-g-cholesterol) for anticancer drug delivery and controlled release

Authors Huang X, Liao W, Zhang G, Kang S, Zhang CY

Received 12 December 2016

Accepted for publication 23 February 2017

Published 21 March 2017 Volume 2017:12 Pages 2215—2226

DOI https://doi.org/10.2147/IJN.S130037

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Farooq Shiekh

Peer reviewer comments 3

Editor who approved publication: Professor Israel (Rudi) Rubinstein


Xiangxuan Huang,1 Wenbo Liao,1 Gang Zhang,1 Shimin Kang,1 Can Yang Zhang2

1School of Chemical Engineering and Energy Technology, Dongguan University of Technology, Dongguan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA, USA

Abstract: A novel amphiphilic pH-sensitive triblock polymer brush (poly(β-amino esters)-g-cholesterol)-b-poly(ethylene glycol)-b-(poly(β-amino esters)-g-cholesterol) ((PAE-g-Chol)-b-PEG-b-(PAE-g-Chol)) was designed and synthesized successfully through a three-step reaction, and their self-assembled polymeric micelles were used as hydrophobic anticancer drug delivery carriers to realize effectively controlled release. The critical micelle concentrations were 6.8 µg/mL, 12.6 µg/mL, 17.4 µg/mL, and 26.6 µg/mL at pH values of 7.4, 6.5, 6.0, and 5.0, respectively. The trend of critical micelle concentrations indicated that the polymer had high stability that could prolong the circulation time in the body. The hydrodynamic diameter and zeta potential of the polymeric micelles were influenced significantly by the pH values. As pH decreased from 7.4 to 5.0, the particle size and zeta potential increased from 205.4 nm to 285.7 nm and from +12.7 mV to +47.0 mV, respectively. The pKb of the polymer was confirmed to be approximately 6.5 by the acid–base titration method. The results showed that the polymer had sharp pH-sensitivity because of the protonation of the amino groups, resulting in transformation of the PAE segment from hydrophobic to hydrophilic. Doxorubicin-loaded polymeric micelles were prepared with a high loading content (20%) and entrapment efficiency (60%) using the dialysis method. The in vitro results demonstrated that drug release rate and cumulative release were obviously dependent on pH values. Furthermore, the drug release mechanism was also controlled by the pH values. The polymer had barely any cytotoxicity, whereas the doxorubicin-loaded system showed high toxicity for HepG2 cells as free drugs. All the results proved that the pH-sensitive triblock polymer brush and its self-assembled micelle might be a potential delivery carrier for anticancer drugs with sustained release.

Keywords: pH-sensitive, micelle, anticancer, drug delivery, controlled release

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