PEG and PEG-peptide based doxorubicin delivery systems containing hydrazone bond

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mPEG and mPEG-peptide based drug delivery systems were prepared by conjugating doxorubicin (DOX) to these carrier molecules via hydrazone bond. The peptide, AT1, with a sequence of CG3H6G3E served as mPEG and doxorubicin attachment site. Histidines were incorporated to the sequence to improve pH responsiveness of the carrier molecule. Hydrodynamic diameters (mean sizes) of mPEG-based drug delivery system (mPEG-HYD-DOX) were measured as 9 ± 0.5 and 7 ± 0.5 nm at pH 7.4 and pH 5.0, respectively. Mean size of the aggregates of the peptide containing drug delivery system, mPEG-AT1-DOX, was determined as 12 ± 2 nm at neutral pH. At pH 5.0, on the other hand, mPEG-AT1-DOX exhibited a size distribution between 20 and 100 nm centered at about 40 nm. Comparison of % DOX release values of the drug delivery systems obtained at pH 7.4 and pH 5.0 indicated that mPEG-AT1-DOX has enhanced pH sensitivity. DOX equivalent absolute IC50 values were obtained as 0.96 ± 0.51, 21.9 ± 5.9, and 5.55 ± 0.75 μg/mL for free DOX, mPEG-HYD-DOX, and mPEG-AT1-DOX, respectively. Considering more pronounced pH sensitivity and cytotoxicity of mPEG-AT1-DOX, the use of both pH responsive functional groups and acid cleavable chemical bond between the carrier molecule and drug can be a promising approach in the design of drug delivery systems for cancer therapy.


pH responsive drug delivery system Doxorubicin Hydrazone bond PEG Peptide Histidine 



The work was financially supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) [grant number 112S554]. İzmir Institute of Technology Biotechnology and Bioengineering Research and Application Center and Research Specialist Özgür Yılmazer are acknowledged for making cytotoxicity tests possible. We thank to Materials Research Center at İzmir Institute of Technology and Research Specialist Mine Bahçeci for AFM experiments. We also thank to Prof. Talat Yalçın and Dr. Ahmet Emin Atik for kindly providing mass spectroscopy data, which were taken at Biological Mass Spectrometry and Proteomics Facility at İzmir Institute of Technology.

Supplementary material

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© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Chemical Engineeringİzmir Institute of TechnologyİzmirTurkey

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