Journal of Polymer Research

, 20:295

pH-responsive micelles composed of poly(ethylene glycol) and cholesterol-modified poly(monomethyl itaconate) as a nanocarrier for controlled and targeted release of piroxicam


  • Zhaleh Pourmoazzen
    • Chemistry Department, Faculty of ScienceAzarbaijan Shahid Madani University
    • Chemistry Department, Faculty of ScienceAzarbaijan Shahid Madani University
  • Ali Akbar Entezami
    • Polymer Laboratory, Organic Chemistry Department, Faculty of ChemistryTabriz University
  • Kazem Nejati Koshki
    • Faculty of Advanced Biomedical SciencesTabriz University of Medical Sciences
Original Paper

DOI: 10.1007/s10965-013-0295-1

Cite this article as:
Pourmoazzen, Z., Bagheri, M., Entezami, A.A. et al. J Polym Res (2013) 20: 295. doi:10.1007/s10965-013-0295-1


A novel monomethyl itaconate-based copolymer (PEG-PMMI-CholC6) bearing cholesteryl (CholC6) and poly(ethylene glycol) (PEG) side chains with specific degrees of side-chain substitution (DSChol = 4.85 and DSPEG = 16.41) was synthesized by performing a reaction involving cholesterol-containing poly(monomethyl itaconate) (PMMI-CholC6) and polyethylene glycol monomethyl ether (PEG, MW∼ 2000). In aqueous solution, reversible pH-responsive micelle-like aggregates of PMMI-CholC6 and PEG-PMMI-CholC6 amphiphilic copolymers formed, with their phase transitions occurring around pH 3.8 and 5.12, respectively. The presence of the PEG groups improved the hydrophilicity of the copolymer and suppressed excessive micelle aggregation. The critical micelle concentration (CMC) of the PEG-PMMI-CholC6 copolymeric micelles at pH 5.12 was about 1 mg/L. DLS and TEM studies revealed that the spherical micelles had mean diameters of <50 nm, which increased in basic solution. On the other hand, upon increasing the pH, the zeta potential decreased from −0.645 to −47.1 due to increased negative charge on the surfaces of the micelles. These pH-responsive micelles were then loaded with piroxicam (PX), a hydrophobic anticancer drug. High drug entrapment efficiencies (>40 %) of the PEG-PMMI-CholC6 micelles were observed due to the enhanced surface hydrophilicity of these micelles. In vitro release studies performed in buffer solutions at pH 1.2, 4.5, and 7.4 indicated that the PEG-PMMI-CholC6 delivery system can act as a stable nanocarrier allowing controlled drug release at target sites in the pH range 4.5–7.4. Interestingly, MTT assays indicated that the PEG-PMMI-CholC6 micelles did not inhibit HeLa cells regrowth, even at high micellar concentrations. These results suggest that PEG-PMMI-CholC6 micelles have great potential to be safely used in tumor-targeting chemotherapy.


Poly(ethylene glycol)Self-assemblyMonomethyl itaconatepH-responsiveAmphiphilic polymersTargeted drug delivery

Copyright information

© Springer Science+Business Media Dordrecht 2013