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

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).

Ultrasonic Film Rehydration Synthesis of Mixed Polylactide Micelles for Enzyme-Resistant Drug Delivery Nanovehicles

“…The intravenous route of administration of PTX is the major method for treatment [ 72 , 73 , 78 , 79 ]. For this purpose, different carriers of amphiphilic and polymeric structures are developing [ 9 , 11 , 15 , 18 , 46 , 61 , 72 , 78 ].…”

“…In contrast to surfactant-based micelles, the CMC of polymer micelles is several magnitudes lower, and some polymer micelles with “frozen” structures do not decompose at all after dilution [ 44 , 45 ]. Polymer micelles are prospective nanocarriers for drug delivery with prolonged circulation in the human body—the hydrophilic part of the block copolymer is responsible for the “masking” of micelles from the reticuloendothelial system and preventing the adsorption of proteins [ 46 , 47 ]. Polymeric micelles are able to avoid capillary filtration [ 48 ] and kidney filtration [ 49 ].…”

Glycopolymer and Poly(β-amino ester)-Based Amphiphilic Block Copolymer as a Drug Carrier

“…Therefore, using sugar moieties as ligands of either GLUTs or CD44 to actively target cancer cells is becoming one of the important strategies in cancer therapy. − Glycopolymers are synthetic macromolecules having pendant sugar moieties and widely used to target cancer cells. ,− They are usually utilized as the hydrophilic segment of amphiphilic block copolymers to fabricate micelles as drug carriers. , One of these glycopolymers is poly­(2-deoxy-2-methacrylamido- d -glucose) (PMAG) mostly obtained by reversible addition fragmentation chain transfer (RAFT) polymerization and has been extensively studied in delivery applications. Since PMAG is hydrophilic, it is usually combined with hydrophobic segments including poly­( l -lysine- co - L -phenylalanine), poly­[( N -(2-aminoethyl) methacrylamide], poly­[ N -[3-( N,N -dimethylamino) propyl] methacrylamide], and poly­( O -cholesteryl methacrylate) to fabricate core–shell micelles. Such polymeric micelles are useful in both passive targeting due to their sizes (enhanced permeation and retention effect) and active targeting via glucose groups leading to decreased systemic toxicity and side effects.…”

“… 51 , 52 One of these glycopolymers is poly(2-deoxy-2-methacrylamido- d -glucose) (PMAG) mostly obtained by reversible addition fragmentation chain transfer (RAFT) polymerization and has been extensively studied in delivery applications. Since PMAG is hydrophilic, it is usually combined with hydrophobic segments including poly( l -lysine- co - L -phenylalanine), 53 poly[( N -(2-aminoethyl) methacrylamide], 54 poly[ N -[3-( N,N -dimethylamino) propyl] methacrylamide], 55 and poly( O -cholesteryl methacrylate) 56 to fabricate core–shell micelles. Such polymeric micelles are useful in both passive targeting due to their sizes (enhanced permeation and retention effect) 57 and active targeting via glucose groups 40 leading to decreased systemic toxicity and side effects.…”

ROS‐Responsive Glycopolymeric Nanoparticles for Enhanced Drug Delivery to Macrophages

“…Moreover, Smith et al showed that polyplexes utilizing poly(methacrylamidoglucopyranose) (PMAG) as a stabilizing block displayed greater colloidal stability than those with PEG as the stabilizing block. PMAG is one of the most prominent glycopolymers used for drug delivery, and it has been incorporated in a variety of nanoparticle formulations for hydrophobic drug delivery, [36] stimuli-responsive drug delivery, [37] and more. However, there has yet to be any investigation of ROS-responsive PMAG nanoparticles that can achieve targeted drug delivery to macrophages.…”