Influence of Hydrophobic Side-Chain Length in Amphiphilic Gradient Copoly(2-oxazoline)s on the Therapeutics Loading, Stability, Cellular Uptake and Pharmacokinetics of Nano-Formulation with Curcumin
Shubhashis Datta,
Veronika Huntošová,
Annamária Jutková,
Róbert Seliga,
Juraj Kronek,
Adriána Tomkova,
Lenka Lenkavská,
Mariana Máčajová,
Boris Bilčík,
Barbora Kundeková,
Ivan Čavarga,
Ewa Pavlova,
Miroslav Šlouf,
Pavol Miškovský,
Daniel Jancura
Affiliations
Shubhashis Datta
Center for Interdisciplinary Biosciences, Technology and Innovation Park, P. J. Safarik University in Košice, Jesenna 5, 04154 Košice, Slovakia
Veronika Huntošová
Center for Interdisciplinary Biosciences, Technology and Innovation Park, P. J. Safarik University in Košice, Jesenna 5, 04154 Košice, Slovakia
Annamária Jutková
Department of Biophysics, Faculty of Science, P. J. Safarik University in Košice, Jesenna 5, 04154 Košice, Slovakia
Róbert Seliga
Center for Interdisciplinary Biosciences, Technology and Innovation Park, P. J. Safarik University in Košice, Jesenna 5, 04154 Košice, Slovakia
Juraj Kronek
Department for Biomaterials Research, Polymer Institute of the Slovak Academy of Sciences, Dubravska Cesta 9, 845 41 Bratislava, Slovakia
Adriána Tomkova
Department of Biophysics, Faculty of Science, P. J. Safarik University in Košice, Jesenna 5, 04154 Košice, Slovakia
Lenka Lenkavská
Department of Biophysics, Faculty of Science, P. J. Safarik University in Košice, Jesenna 5, 04154 Košice, Slovakia
Mariana Máčajová
Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dubravska Cesta 9, 840 05 Bratislava, Slovakia
Boris Bilčík
Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dubravska Cesta 9, 840 05 Bratislava, Slovakia
Barbora Kundeková
Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dubravska Cesta 9, 840 05 Bratislava, Slovakia
Ivan Čavarga
Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dubravska Cesta 9, 840 05 Bratislava, Slovakia
Ewa Pavlova
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho Nam. 2, 162 06 Prague, Czech Republic
Miroslav Šlouf
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho Nam. 2, 162 06 Prague, Czech Republic
Pavol Miškovský
Center for Interdisciplinary Biosciences, Technology and Innovation Park, P. J. Safarik University in Košice, Jesenna 5, 04154 Košice, Slovakia
Daniel Jancura
Department of Biophysics, Faculty of Science, P. J. Safarik University in Košice, Jesenna 5, 04154 Košice, Slovakia
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.
