Macromolecular Design and Engineering of New Amphiphilic N-Vinylpyrrolidone Terpolymers for Biomedical Applications.

New amphiphilic VP-(di)methacrylate terpolymers of different monomer compositions and topologies have been synthesized by radical polymerization in toluene without any growth regulator of polymer chains. Their structures and properties in solid state and water solution were studied by double-detector size-exclusion chromatography; IR-, 1H, and 13C NMR-spectroscopy; DLS, TEM, TG, and DSC methods. The composition of the VP-AlkMA-TEGDM monomer mixture has been established to regulate the topology of the resulting macromolecules. The studied terpolymers presented on TEM images as individual low-contrast particles and their conglomerates of various sizes with highly ordered regions; in general, they are amorphous structures. None of the terpolymers demonstrated cytotoxic effects for noncancerous Vero and tumor HeLa cells. Hydrophobic D-α-tocopherol (TP) was encapsulated in terpolymer nanoparticles (NPs), and its antioxidant activity was evaluated by ABTS (radical monocation 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)) or DPPH (2,2'-diphenyl-1-picrylhydrazyl) methods. The reaction efficiency depends on the TP-NP type. The IC50 values for the decolorization reaction of ABTS•+ and DPPH inhibition in the presence of initial and encapsulated TP were obtained.

Nanoparticles of N-Vinylpyrrolidone Amphiphilic Copolymers and Pheophorbide a as Promising Photosensitizers for Photodynamic Therapy: Design, Properties and In Vitro Phototoxic Activity.

A series of nanoparticles (NPs) with a hydrodynamic radius from 20 to 100 nm in PBS was developed over the solubilization of hydrophobic dye methyl pheophorbide a (chlorin e6 derivative) by amphiphilic copolymers of N-vinylpyrrolidone with (di)methacrylates. Photophysical properties and biological activity of the NPs aqueous solution were studied. It was found that the dye encapsulated in the copolymers is in an aggregated state. However, its aggregation degree decreases sharply, and singlet oxygen quantum yield and the fluorescence signal increase upon the interaction of these NPs with model biological membranes-liposomes or components of a tissue homogenate. The phototoxic effect of NPs in HeLa cells exceeds by 1.5-2 times that of the reference dye chlorin e6 trisodium salt-one of the most effective photosensitizers used in clinical practice. It could be explained by the effective release of the hydrophobic photosensitizer from the NPs into biological structures. The demonstrated approach can be used not only for the encapsulation of hydrophobic photosensitizers for PDT but also for other drugs, and N-vinylpyrrolidone amphiphilic copolymers show promising potential as a modern platform for the design of targeted delivery vehicles.