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Synthesis of folate- pegylated polyester nanoparticles encapsulating ixabepilone for targeting folate receptor overexpressing breast cancer cells

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Abstract

The aim of this study was the preparation of novel polyester nanoparticles based on folic acid (FA)–functionalized poly(ethylene glycol)–poly(propylene succinate) (PEG–PPSu) copolymer and loaded with the new anticancer drug ixabepilone (IXA). These nanoparticles may serve as a more selective (targeted) treatment of breast cancer tumors overexpressing the folate receptor. The synthesized materials were characterized by 1H-NMR, FTIR, XRD and DSC. The nanoparticles were prepared by a double emulsification and solvent evaporation method and characterized with regard to their morphology by scanning electron microscopy, drug loading with HPLC–UV and size by dynamic light scattering. An average size of 195 nm and satisfactory drug loading efficiency (3.5 %) were observed. XRD data indicated that IXA was incorporated into nanoparticles in amorphous form. The nanoparticles exhibited sustained drug release properties in vitro. Based on in vitro cytotoxicity studies, the blank FA–PEG–PPSu nanoparticles were found to be non-toxic to the cells. Fluorescent nanoparticles were prepared by conjugating Rhodanine B to PEG–PPSu, and live cell, fluorescence, confocal microscopy was applied in order to demonstrate the ability of FA–PEG–PPSu nanoparticles to enter into human breast cancer cells expressing the folate receptor.

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Acknowledgments

The authors wish to acknowledge co-funding of this research by European Union-European Regional Development Fund and Greek Ministry of Εducation/EYDE-ETAK through program ESPA 2007-2013/EPAN II/Action “SYNERGASIA” (09SYN-41-659).

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Authors and Affiliations

  1. Department of Chemistry, Aristotle University of Thessaloniki, 54 124, Thessaloniki, Macedonia, Greece

    P. Siafaka, M. Betsiou & D. Bikiaris

  2. Department of Molecular Biology and Genetics, Democritus University of Thrace, Xanthi, Greece

    A. Tsolou, E. Angelou, B. Agianian & M. Koffa

  3. Pharmathen S.A, Pharmaceutical Industry, Dervenakion Str6, 153 51, Attiki, Greece

    S. Chaitidou & E. Karavas

  4. Department of Pharmacy, University of Patras, 26500, Patras, Greece

    K. Avgoustakis

Authors
  1. P. Siafaka
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  2. M. Betsiou
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  4. E. Angelou
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  5. B. Agianian
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Correspondence to D. Bikiaris.

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Siafaka, P., Betsiou, M., Tsolou, A. et al. Synthesis of folate- pegylated polyester nanoparticles encapsulating ixabepilone for targeting folate receptor overexpressing breast cancer cells. J Mater Sci: Mater Med 26, 275 (2015). https://doi.org/10.1007/s10856-015-5609-x

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  • DOI: https://doi.org/10.1007/s10856-015-5609-x

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