Self-Assembly, Drug Encapsulation, and Cellular Uptake of Block and Gradient Copolymers of 2-Methyl-2-oxazine and 2-n-Propyl/butyl-2-oxazoline
- David BabukaDavid BabukaInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho sq. 2, Prague 6 162 06, Czech RepublicDepartment of Biophysics, Institute of Physics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 3, Prague 2 121 16, Czech RepublicMore by David Babuka
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- Kristyna KolouchovaKristyna KolouchovaInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho sq. 2, Prague 6 162 06, Czech RepublicDepartment of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Hlavova 8, Prague 2 128 00, Czech RepublicMore by Kristyna Kolouchova
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- Lenka LoukotovaLenka LoukotovaInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho sq. 2, Prague 6 162 06, Czech RepublicMore by Lenka Loukotova
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- Ondrej SedlacekOndrej SedlacekDepartment of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Hlavova 8, Prague 2 128 00, Czech RepublicDepartment of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Ghent, BelgiumMore by Ondrej Sedlacek
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- Ondrej GroborzOndrej GroborzInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho sq. 2, Prague 6 162 06, Czech RepublicInstitute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo sq. 542, Prague 6 162 06, Czech RepublicInstitute of Biophysics and Informatics, Charles University, First Faculty of Medicine, Salmovská 1, Prague 2 120 00, Czech RepublicMore by Ondrej Groborz
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- Aneta SkarkovaAneta SkarkovaDepartment of Cell Biology, Charles University, Vinicna 7, Prague 12843, Czech RepublicBiotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (BIOCEV), Prumyslova 595, Vestec u Prahy 25242, Czech RepublicMore by Aneta Skarkova
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- Alexander ZhigunovAlexander ZhigunovInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho sq. 2, Prague 6 162 06, Czech RepublicMore by Alexander Zhigunov
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- Ewa PavlovaEwa PavlovaInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho sq. 2, Prague 6 162 06, Czech RepublicMore by Ewa Pavlova
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- Richard Hoogenboom*Richard Hoogenboom*Email: [email protected]Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Ghent, BelgiumMore by Richard Hoogenboom
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- Martin Hruby*Martin Hruby*Email: [email protected]Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho sq. 2, Prague 6 162 06, Czech RepublicMore by Martin Hruby
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- Petr StepanekPetr StepanekInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho sq. 2, Prague 6 162 06, Czech RepublicMore by Petr Stepanek
Abstract
Self-assembled amphiphilic polymers have been extensively studied for various biomedical applications, as they show advantageous properties for diagnosis and therapy. In this work, we extensively compared amphiphilic copolymers of the hydrophilic monomer 2-methyl-2-oxazine (MeOzi) and the thermoresponsive or hydrophobic monomers 2-propyl-2-oxazoline (PrOx) or 2-butyl-2-oxazoline (BuOx) in both block and gradient monomer distributions. Such a head-to-head comparison between block and gradient copolymers, which has thus far been mostly missing in the available literature, should provide important insight into the differences and similarities between these two architectures. We investigated the properties of our polymers using a wide array of analytical methods, including dynamic light scattering (DLS), small-angle neutron (SANS) and X-ray scattering (SAXS), one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy, transmission electron microscopy (TEM), drug loading (DL), cellular uptake, and cytotoxicity studies. Most of the studied polymers formed self-assembled nanoparticles, but their properties varied with the monomer ratio, polymer length, and polymer architecture, and these factors could be used to fine-tune the properties of the polymer to meet the demands of the desired application. Both block and gradient copolymers showed similar critical association concentrations and DL properties for the antituberculosis drug rifampicin. Finally, we confirmed that the nanoparticles could be internalized by macrophages, which indicates great potential for the utilization of these nanoparticles in drug delivery.
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