TY - JOUR

T1 - Bio-inspired amphiphilic block-copolymers based on synthetic glycopolymer and poly (amino acid) as potential drug delivery systems

AU - Levit, Mariia

AU - Zashikhina, Natalia

AU - Vdovchenko, Alena

AU - Dobrodumov, Anatoliy

AU - Zakharova, Natalya

AU - Kashina, Anna

AU - Rühl, Eckart

AU - Lavrentieva, Antonina

AU - Scheper, Thomas

AU - Tennikova, Tatiana

AU - Korzhikova-Vlakh, Evgenia

N1 - Funding information: The research was supported financially by the Russian Foundation for Basic Research (RFBR, research project no. 18-33-01018) and the G-RISC scholarship program for A. Vdovchenko and N. Zashikhina (projects #B-2017a-2 and #C-2018b-5, respectively). ER acknowledges DFG for funding (grant no. RU 420/12-1).

PY - 2020/1/10

Y1 - 2020/1/10

N2 - 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.

AB - 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.

KW - Blend

KW - Nanocomposites

KW - Physical properties

KW - Poly(vinylidene fluoride)

KW - Polyamide 6

KW - Drug delivery systems

KW - Amphiphilic block copolymers

KW - Poly(amino acids)

KW - Nanoparticles

KW - Modification of terminal groups

KW - Paclitaxel

KW - Redox-responsive systems

KW - Synthetic glycopolymers

UR - http://www.scopus.com/inward/record.url?scp=85082653219&partnerID=8YFLogxK

U2 - 10.3390/polym12010183

DO - 10.3390/polym12010183

M3 - Article

C2 - 32284516

VL - 12

SP - 1

EP - 27

JO - Polymers

JF - Polymers

SN - 2073-4360

IS - 1

M1 - 183

ER -