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.

Mariia Levit,Eugene Sivtsov,Apollinariia Dzhuzha,Natalia Zashikhina,Tatiana Tennikova,Elena Katernyuk,Alena Vdovchenko,Evgenia Korzhikova-Vlakh,Alexey Gostev,Antonina Lavrentieva

doi:10.3390/ijms222111457

Abstract

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(N-methacrylamido-d-glucose) or poly(N-vinyl succinamic acid) as a hydrophilic fragment and poly(O-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 1H 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).

Highlights

Over the last decade, attention to nanomaterials based on self-assembling amphiphilic polymers has been steadily growing [1,2]
The synthesis of well-defined polymers by radical addition–fragmentation chain-transfer (RAFT) polymerization is limited by the selection of a suitable chain-transfer agent (CTA) as well as a solvent capable of dissolving both the monomer and the resulting product
The synthesis of a diblock-copolymer by RAFT polymerization includes a synthesis of a homopolymer, which further serves as a macro-RAFT agent in RAFT copolymerization with another monomer

Summary

Introduction

Attention to nanomaterials based on self-assembling amphiphilic polymers has been steadily growing [1,2]. With an increase in the concentration of the amphiphilic copolymer in solution, the free energy of the system increases due to unfavorable interactions between water molecules and the hydrophobic fragment of the macromolecule. This leads to the self-induced structuring of polymer macromolecules to decrease the entropy of the system. The formation of spherical or cylindrical polymer micelles, as well as polymer vesicles or polymersomes, is possible [5] All these nanoparticles are suitable for encapsulation of hydrophobic and amphiphilic drugs [6,7,8,9]

Methods

Results

Conclusion