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

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).

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Bio-Inspired Amphiphilic Block-Copolymers Based on Synthetic Glycopolymer and Poly(Amino Acid) as Potential Drug Delivery Systems

Polymers ◽

10.3390/polym12010183 ◽

2020 ◽

Vol 12 (1) ◽

pp. 183 ◽

Cited By ~ 1

Author(s):

Mariia Levit ◽

Natalia Zashikhina ◽

Alena Vdovchenko ◽

Anatoliy Dobrodumov ◽

Natalya Zakharova ◽

...

Keyword(s):

Amino Acid ◽

Block Copolymers ◽

Raft Polymerization ◽

Amphiphilic Block Copolymers ◽

Breast Adenocarcinoma ◽

Hydrodynamic Diameter ◽

Amphiphilic Copolymers ◽

Lung Carcinoma Cells ◽

Biodegradable Poly ◽

Human Lung Carcinoma

In this work, a method to prepare hybrid amphiphilic block copolymers consisting of biocompatible synthetic glycopolymer with non-degradable backbone and biodegradable poly(amino acid) (PAA) was developed. The glycopolymer, poly(2-deoxy-2-methacrylamido-D-glucose) (PMAG), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Two methods for modifying the terminal dithiobenzoate-group of PMAG was investigated to obtain the macroinitiator bearing a primary aliphatic amino group, which is required for ring-opening polymerization of N-carboxyanhydrides of hydrophobic α-amino acids. The synthesized amphiphilic block copolymers were carefully analyzed using a set of different physico-chemical methods to establish their composition and molecular weight. The developed amphiphilic copolymers tended to self-assemble in nanoparticles of different morphology that depended on the nature of the hydrophobic amino acid present in the copolymer. The hydrodynamic diameter, morphology, and cytotoxicity of polymer particles based on PMAG-b-PAA were evaluated using dynamic light scattering (DLS) and transmission electron microscopy (TEM), as well as CellTiter-Blue (CTB) assay, respectively. The redox-responsive properties of nanoparticles were evaluated in the presence of glutathione taken at different concentrations. Moreover, the encapsulation of paclitaxel into PMAG-b-PAA particles and their cytotoxicity on human lung carcinoma cells (A549) and human breast adenocarcinoma cells (MCF-7) were studied.

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Stimuli responsive amphiphilic block copolymers for aqueous media synthesised via reversible addition fragmentation chain transfer polymerisation (RAFT)

Polymer ◽

10.1016/j.polymer.2005.03.101 ◽

2005 ◽

Vol 46 (18) ◽

pp. 7726-7740 ◽

Cited By ~ 169

Author(s):

Murat Mertoglu ◽

Sébastien Garnier ◽

André Laschewsky ◽

Katja Skrabania ◽

Joachim Storsberg

Keyword(s):

Block Copolymers ◽

Chain Transfer ◽

Aqueous Media ◽

Amphiphilic Block Copolymers ◽

Stimuli Responsive ◽

Reversible Addition

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Synthesis and self-association in aqueous media of poly(ethylene oxide)/poly(ethyl glycidyl carbamate) amphiphilic block copolymers

Polymer ◽

10.1016/j.polymer.2006.05.030 ◽

2006 ◽

Vol 47 (14) ◽

pp. 4905-4915 ◽

Cited By ~ 36

Author(s):

Philip Dimitrov ◽

Alicja Utrata-Wesołek ◽

Stanislav Rangelov ◽

Wojciech Wałach ◽

Barbara Trzebicka ◽

...

Keyword(s):

Block Copolymers ◽

Ethylene Oxide ◽

Aqueous Media ◽

Amphiphilic Block Copolymers ◽

Poly Ethylene Oxide ◽

Self Association ◽

Poly Ethylene ◽

Glycidyl Carbamate

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Synthesis of amphiphilic block copolymers based on poly(dimethylsiloxane) via fragmentation chain transfer (RAFT) polymerization

Polymer ◽

10.1016/j.polymer.2004.04.041 ◽

2004 ◽

Vol 45 (13) ◽

pp. 4383-4389 ◽

Cited By ~ 51

Author(s):

Tommy S.C Pai ◽

Christopher Barner-Kowollik ◽

Thomas P Davis ◽

Martina H Stenzel

Keyword(s):

Block Copolymers ◽

Chain Transfer ◽

Raft Polymerization ◽

Amphiphilic Block Copolymers

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Synthesis of Y-shaped amphiphilic copolymers by macromolecular azo coupling reaction

RSC Advances ◽

10.1039/c4ra14926b ◽

2015 ◽

Vol 5 (13) ◽

pp. 9476-9481 ◽

Cited By ~ 22

Author(s):

Jilei Wang ◽

Yuqi Zhou ◽

Xiaogong Wang ◽

Yaning He

Keyword(s):

Block Copolymers ◽

Coupling Reaction ◽

Amphiphilic Block Copolymers ◽

Amphiphilic Copolymers ◽

Azo Coupling

The synthesis of well-defined AB2 Y-shaped amphiphilic block copolymers by macromolecular azo coupling reaction is reported.

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A facile one-pot strategy for preparation of small polymer nanoparticles by self-crosslinking of amphiphilic block copolymers containing acyl azide groups in aqueous media

Soft Matter ◽

10.1039/c0sm01132k ◽

2011 ◽

Vol 7 (8) ◽

pp. 3956 ◽

Cited By ~ 15

Author(s):

Haiting Zheng ◽

Xiaodong Ye ◽

Hu Wang ◽

Lifeng Yan ◽

Ruke Bai ◽

...

Keyword(s):

Block Copolymers ◽

Aqueous Media ◽

Polymer Nanoparticles ◽

Amphiphilic Block Copolymers ◽

One Pot ◽

Acyl Azide

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Synthesis of amphiphilic block copolymers via ring opening polymerization and reversible addition‐fragmentation chain transfer polymerization

Journal of Polymer Science ◽

10.1002/pol.20200719 ◽

2020 ◽

Vol 59 (1) ◽

pp. 43-58

Author(s):

Patrizia P. Smith ◽

Stephen G. Boyes

Keyword(s):

Block Copolymers ◽

Ring Opening ◽

Chain Transfer ◽

Ring Opening Polymerization ◽

Amphiphilic Block Copolymers ◽

Reversible Addition ◽

Chain Transfer Polymerization

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Synthesis of Cationic Amphiphilic Block Copolymers Poly(4-vinylbenzyltriethylammonium chloride)-b-Poly(styrene) and Their Self-Assembly in Aqueous Solution

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2016.10701 ◽

2016 ◽

Vol 16 (4) ◽

pp. 4239-4246

Author(s):

Zhijiao Dong ◽

Bingbing Yang ◽

Zhifeng Fu ◽

Yan Shi

Keyword(s):

Block Copolymers ◽

Formation Process ◽

Self Assembly ◽

Chain Transfer ◽

Amphiphilic Block Copolymers ◽

The Core ◽

Reversible Addition ◽

The Common ◽

Spherical Micelles ◽

Large Compound

Well defined two kinds of cationic amphiphilic block copolymers Poly(4-vinylbenzyltriethylammonium chloride)-b-Poly(styrene) are synthesized by combining reversible addition fragmentation chain transfer polymerizations and post-polymerization quaternization. Block copolymers are characterized by GPC and 1HNMR. The self-assembly behaviors of the block copolymers are studied, which are characterized by TEM. For Poly(4-vinylbenzyltriethylammonium chloride)13-b-Poly(styrene)136, crew-cut spherical micelles are obtained by using DMF as the initial common solvent, and the majority of the pearl series aggregates and a small amount of rod-like aggregates are all observed by using the mixture of DMF and THF as the initial common solvent. The formation process of rod-like aggregates is proposed in three steps: the micellization of copolymer chains, the formation of pearl series aggregates from the collision and fusion of individual initial spherical micelles, and the transformation from pearl series aggregates to rod-like aggregates. For Poly(4- vinylbenzyltriethylammonium chloride)18-b-Poly(styrene)370, large compound micelles and complicated spherical aggregates and small vesicles are all obtained. The formation process of small vesicles is also proposed in three steps: the formation of initial spherical micelles with some hydrophilic block Poly(4-vinylbenzyltriethylammonium chloride) embedded in the core, the removing of the outer layer common solvent, and solvent nucleation in the center. It should be noted that solvent nucleation is critical, because of the hydrophilic block Poly(4-vinylbenzyltriethylammonium chloride) and the common solvent and water embedded in the core of the initial spherical micelles.

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Multiple and Co-Nanoprecipitation Studies of Branched Hydrophobic Copolymers and A–B Amphiphilic Block Copolymers, Allowing Rapid Formation of Sterically Stabilized Nanoparticles in Aqueous Media

Macromolecules ◽

10.1021/acs.macromol.5b00099 ◽

2015 ◽

Vol 48 (6) ◽

pp. 1883-1893 ◽

Cited By ~ 6

Author(s):

Jane Ford ◽

Pierre Chambon ◽

Jocelyn North ◽

Fiona L. Hatton ◽

Marco Giardiello ◽

...

Keyword(s):

Block Copolymers ◽

Aqueous Media ◽

Amphiphilic Block Copolymers ◽

Rapid Formation

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Synthesis and Characterization of Macroinitiators Based on Polyorganophosphazenes for the Ring Opening Polymerization of N-Carboxyanhydrides

Polymers ◽

10.3390/polym13091446 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1446

Author(s):

Natalia Zashikhina ◽

Marina Vasileva ◽

Olga Perevedentseva ◽

Irina Tarasenko ◽

Tatiana Tennikova ◽

...

Keyword(s):

Amino Acids ◽

Degradation Rate ◽

Aqueous Media ◽

Delivery Systems ◽

In Vitro Cytotoxicity ◽

Side Chains ◽

Amphiphilic Copolymers ◽

Hybrid Copolymers

Among the various biocompatible amphiphilic copolymers, biodegradable ones are the most promising for the preparation of drug delivery systems since they are destroyed under physiological conditions, that, as a rule, reduce toxicity and provide controlled release of the drug. Hybrid graft-copolymers consisting of the main inorganic polyphosphazene chain and polypeptide side chains are of considerable interest for the development of delivery systems with a controlled degradation rate, since the main and side chains will have different degradation mechanisms (chemical and enzymatic hydrolysis, respectively). Variable particle degradation rate, controlled by the adjusting the composition of substituents, will allow selective delivery in vivo and controlled drug release. The present work proposes the preparation of biodegradable macroinitiators based on polyorganophosphazenes for the synthesis of hybrid copolymers. Synthesis of novel biodegradable macroinitiators based on polyorganophosphazenes was performed via macromolecular substitution of a polydichlorophosphazene chain with the sodium alcoholates, amines and amino acids. The composition of copolymers obtained was calculated using NMR. These polyorganophosphazenes bearing primary amino groups can be considered as convenient macroinitiators for the polymerization of NCA of α-amino acids in order to prepare hybrid copolymers polyphosphazene-graft-polypeptide. The developed macroinitiators were amphiphilic and self-assembled in the aqueous media into nanoparticles. Furthermore, the ability to encapsulate and release a model substance was demonstrated. In addition, the in vitro cytotoxicity of synthesized polymers was evaluated using two cell lines.

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