Self-Assembly, Drug Encapsulation, and Cellular Uptake of Block and Gradient Copolymers of 2-Methyl-2-oxazine and 2-n-Propyl/butyl-2-oxazoline
MACROMOLECULES(2021)
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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Key words
drug encapsulation,gradient copolymers,self-assembly
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