Self-Assembled Nanoparticles Based on Block-Copolymers of Poly(2-Deoxy-2-methacrylamido-d-glucose)/Poly( N -Vinyl Succinamic Acid) with Poly( O -Cholesteryl Methacrylate) for Delivery of Hydrophobic Drugs

• Published in: International journal of molecular sciences 2021-10, Vol.22 (21), p.11457
• Main Authors: Levit, Mariia, Vdovchenko, Alena, Dzhuzha, Apollinariia, Zashikhina, Natalia, Katernyuk, Elena, Gostev, Alexey, Sivtsov, Eugene, Lavrentieva, Antonina, Tennikova, Tatiana, Korzhikova-Vlakh, Evgenia
• Format: Article
• Language: English
• Subjects: Addition polymerization; Adenocarcinoma; Amino acids; amphiphilic copolymers; Aqueous solutions; bio-inspired copolymers; Biocompatibility; Biodegradation; Biological activity; Biomimetics; Block copolymers; Carbon; Cell Line; Cholesterol; controlled radical polymerization; Copolymers; Cytotoxicity; Drug delivery; Drug delivery systems; Drug Delivery Systems - methods; Dynamic stability; Epithelial cells; Epithelium; Fourier analysis; Glucose; HEK293 Cells; Humans; Hydrophilicity; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Infrared analysis; Infrared spectroscopy; Light scattering; Lung cancer; Macromolecules; Macrophages; Methacrylates - chemistry; Molecular weight; Morphology; Nanomaterials; Nanoparticles; Nanoparticles - chemistry; Nanotechnology; NMR; Nuclear magnetic resonance; Paclitaxel; Paclitaxel - administration & dosage; Photon correlation spectroscopy; polymer nanoparticles; Polymerization; Polymers; Polymers - chemistry; Quantum dots; Reagents; Self-assembly; Thermal stability; Thermogravimetric analysis; Transmission electron microscopy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111457

The self-assembly of amphiphilic block-copolymers is a convenient way to obtain soft nanomaterials of different morphology and scale. In turn, the use of a biomimetic approach makes it possible to synthesize polymers with fragments similar to natural macromolecules but more resistant to biodegradation. In this study, we synthesized the novel bio-inspired amphiphilic block-copolymers consisting of poly( -methacrylamido-d-glucose) or poly( -vinyl succinamic acid) as a hydrophilic fragment and poly( -cholesteryl methacrylate) as a hydrophobic fragment. Block-copolymers were synthesized by radical addition-fragmentation chain-transfer (RAFT) polymerization using dithiobenzoate or trithiocarbonate chain-transfer agent depending on the first monomer, further forming the hydrophilic block. Both homopolymers and copolymers were characterized by H NMR and Fourier transform infrared spectroscopy, as well as thermogravimetric analysis. The obtained copolymers had low dispersity (1.05-1.37) and molecular weights in the range of ~13,000-32,000. The amphiphilic copolymers demonstrated enhanced thermal stability in comparison with hydrophilic precursors. According to dynamic light scattering and nanoparticle tracking analysis, the obtained amphiphilic copolymers were able to self-assemble in aqueous media into nanoparticles with a hydrodynamic diameter of approximately 200 nm. An investigation of nanoparticles by transmission electron microscopy revealed their spherical shape. The obtained nanoparticles did not demonstrate cytotoxicity against human embryonic kidney (HEK293) and bronchial epithelial (BEAS-2B) cells, and they were characterized by a low uptake by macrophages in vitro. Paclitaxel loaded into the developed polymer nanoparticles retained biological activity against lung adenocarcinoma epithelial cells (A549).