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

Abstract

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.

Thiolated-Polymer-Based Nanoparticles as an Avant-Garde Approach for Anticancer Therapies—Reviewing Thiomers from Chitosan and Hyaluronic Acid

“…Levit et al also recently demonstrated that NPs consisting of biodegradable poly(amino acid) and poly(2-deoxy-2-methacrylamido-D-glucose) (PMAG) can function as a reliable delivery system for paclitaxel in glutathione-rich conditions [159]. Great results were achieved when evaluated in A549 (human lung carcinoma cells) and MCF-7 (human breast adenocarcinoma) cells.…”

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

“…They can be fully biodegradable, such as poly(lactic acid) [ 14 ] or poly(L-amino acids) [ 8 ], or possess non-biodegradable carbon–carbon backbone bearing cleavable bio-inspired side units, such as saccharide fragments [ 15 ]. In order to increase the lifetime of delivery systems based on amphiphilic copolymers, the hybrid systems that combine biodegradable and non-biodegradable polymer fragments can be a matter of choice [ 16 , 17 ]. Currently, a number of amphiphilic hybrid and fully synthetic copolymers have been synthesized.…”

“…Poly(ethylene glycol) (PEG), polyoxazolines, different polysaccharides, hydrophilic poly(amino acids), and synthetic glycopolymers are usually used as hydrophilic blocks, while aliphatic polyesters (poly(lactic acid) (PLA), polycaprolactone, etc. ), polycarbonates, hydrophobic poly(amino acids), polystyrene, poly(butyl methacrylate), etc., are utilized as hydrophobic blocks [ 17 , 18 , 19 , 20 , 21 , 22 ].…”

“…Moreover, RAFT polymerization is widely used for the synthesis of block-copolymers where a homopolymer, formed during the first step, serves as a macro-RAFT agent for the synthesis of the second block from another monomer [ 39 ]. Recently, the successful syntheses of well-defined glycopolymers [ 24 , 40 ] and their copolymers with poly(diethylene glycol methacrylate) [ 35 ], azobenzene methacrylate [ 41 ], N -(2-aminoethyl)methacrylamide [ 42 ], etc., by RAFT polymerization or a combination of RAFT with other polymerization techniques, such as ring-opening polymerization [ 17 , 43 ] or click reactions [ 23 ], were reported.…”

Self‐Assembled Star‐Shaped sPCL–PEG Copolymer Nanomicelles with pH‐Sensitivity for Anticancer Drug Delivery

“…[ 1–4 ] The increasing interest for amphiphilic copolymers as drug delivery carriers is mainly related to their characteristic self‐assembling tendency. [ 5,6 ] Amphiphilic copolymers can assemble spontaneously into highly ordered nanoscopic core–shell micelles. The hydrophobic segments of amphiphilic copolymer form the core region of the micelle, while the hydrophilic blocks form outer shell.…”