Due to the simple one-step preparation method and a promising application in biomedical research, amphiphilic gradient copoly(2-oxazoline)s are gaining more and more interest compared to their analogous block copolymers. In this work, the curcumin solubilization ability was tested for a series of amphiphilic gradient copoly(2-oxazoline)s with different lengths of hydrophobic side-chains, consisting of 2-ethyl-2-oxazoline as a hydrophilic monomer and 2-(4-alkyloxyphenyl)-2-oxazoline as a hydrophobic monomer. It is shown that the length of the hydrophobic side-chain in the copolymers plays a crucial role in the loading of curcumin onto the self-assembled nanoparticles. The kinetic stability of self-assembled nanoparticles studied using FRET shows a link between their integrity and cellular uptake in human glioblastoma cells. The present study demonstrates how minor changes in the molecular structure of gradient copoly(2-oxazoline)s can lead to significant differences in the loading, stability, cytotoxicity, cellular uptake, and pharmacokinetics of nano-formulations containing curcumin. The obtained results on the behavior of the complex of gradient copoly(2-oxazoline)s and curcumin may contribute to the development of effective next-generation polymeric nanostructures for biomedical applications.

Cassovia New Industry Cluster Tr SNP 1 04001 Košice Slovakia

Center for Interdisciplinary Biosciences Technology and Innovation Park P J Safarik University in Košice Jesenna 5 04154 Košice Slovakia

Department for Biomaterials Research Polymer Institute of the Slovak Academy of Sciences Dubravska Cesta 9 845 41 Bratislava Slovakia

Department of Biophysics Faculty of Science P J Safarik University in Košice Jesenna 5 04154 Košice Slovakia

Institute of Animal Biochemistry and Genetics Centre of Biosciences Slovak Academy of Sciences Dubravska Cesta 9 840 05 Bratislava Slovakia

Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovskeho Nam 2 162 06 Prague Czech Republic

SAFTRA Photonics s r o Moldavska Cesta 51 04011 Košice Slovakia

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