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pH-responsive nanosized-micelles based on poly(monomethylitaconate)-co-poly(dimethylaminoethyl methacrylate) and cholesterol side chains effect on pH change-induced release of piroxicam

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Abstract

Novel double hydrophilic poly(monomethylitaconate)-co-poly(N,N-dimethylaminoethyl methacrylate) (PMMI-co-PDMAEMA) synthesized via free radical polymerization of corresponding monomers with defined molar ratios in the presence of K2S2O8 as an initiator in an aqueous solution. The resulting copolymer was subsequently converted to a cholesterol conjugate (PMMICholC6-co-PDMAEMA) by esterification reaction with 6-cholesteryl-1-hexanol (CholC6). Two copolymers self-assembled into micelles by simply adjusting the solution pH at room temperature. The non-conjugated polymer had a sharp transition at pH 5. TEM and DLS studies showed that both micelles were spherical in shape with a mean diameter around 85 and 26 nm, respectively. Piroxicam (PX) as a hydrophobic model drug was encapsulated into micelles. The results indicated that PMMICholC6-co-PDMAEMA micelles were able to load more amounts of drug than PMMI-co-PDMAEMA micelles which could be attributed to the strong hydrophobic interactions of cholesterol molecules in the core. In vitro release studies demonstrated that PX release from PMMI-co-PDMAEMA micelles was significantly fast at physiological pH compared with mildly acidic pH 4.5. However, at pH 4.5, PMMICholC6-co-PDMAEMA micelles, with core-shell-corona structure, released loaded drug molecules faster than pH 7.4 which contained a relatively steady drug release profile. In summary, cholesterol-modified micelles could be introduced as stable and effective pH responsive nanocarriers to make a promising system for enhancing the efficacy of hydrophobic drugs in cancer cells for improved cancer therapy.

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Acknowledgments

The authors would like to thank Research Vice Chancellor of Azarbaijan Shahid Madani University for financial support of this research. The authors’ warm thanks are also extended to Dr. H. Razmi and Mr. Rahim Mohammad-Rezaei for their useful spectroscopic assistances and Mr. B. Ramazani for him English assistance.

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Authors and Affiliations

  1. Chemistry Department, Science Faculty, Azarbaijan Shahid Madani University, P.O. Box: 53714-161, 5375171379, Tabriz, Iran

    Massoumeh Bagheri & Zhaleh Pourmoazzen

  2. Polymer Laboratory, Organic Chemistry department, Chemistry Faculty, Tabriz University, Tabriz, Iran

    Ali Akbar Entezami

Authors
  1. Massoumeh Bagheri
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  2. Zhaleh Pourmoazzen
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  3. Ali Akbar Entezami
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Correspondence to Massoumeh Bagheri.

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Bagheri, M., Pourmoazzen, Z. & Entezami, A.A. pH-responsive nanosized-micelles based on poly(monomethylitaconate)-co-poly(dimethylaminoethyl methacrylate) and cholesterol side chains effect on pH change-induced release of piroxicam. J Polym Res 20, 231 (2013). https://doi.org/10.1007/s10965-013-0231-4

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  • DOI: https://doi.org/10.1007/s10965-013-0231-4

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