Synthesis of alkyl‐modified poly(sodium glutamate)s for preparation of polymer‐protein nanoparticles in combination with N,N,N‐trimethyl chitosan |
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| Authors: | David Pahovnik Milijana Grujić Mateja Cegnar Janez Kerč Ema Žagar |
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| Affiliation: | 1. National Institute of Chemistry, Laboratory for Polymer Chemistry and Technology, , SI‐1001 Ljubljana, Slovenia;2. Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, , SI‐1526 Ljubljana, Slovenia;3. University of Ljubljana, Faculty of Pharmacy, , SI‐1000 Ljubljana, Slovenia |
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| Abstract: | The negatively charged, water‐soluble, hydrophobically modified poly(sodium glutamate)s containing different amounts of alkyl grafts were synthesized. First, poly(γ‐benzyl‐L‐glutamate) was prepared by ring‐opening polymerization of the corresponding N‐carboxyanhydride, which was in the next step aminolysed with octylamine. After removal of the remaining benzyl protective groups, the alkyl‐modified poly(sodium glutamate)s [P(Glu‐oa)] were obtained and, together with the oppositely charged N,N,N‐trimethyl chitosan (TMC), used for the preparation of nanoparticles (NPs) of a recombinant granulocyte colony‐stimulating factor (GCSF) protein by polyelectrolyte complexation method. It is observed that, beside electrostatic interaction, the hydrophobic grafts on poly(sodium glutamate)s significantly contribute to association efficiency (AE) with GCSF protein. The addition of TMC solution to the dispersion of GCSF/P(Glu‐oa) complexes results in formation of much more defined NPs with high AE and final protein loading. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2976–2985 |
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| Keywords: | drug delivery systems nanoparticles peptides proteins polyelectrolytes |
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