Biocompatible Nanoparticles Based on Amphiphilic Random Polypeptides and Glycopolymers as Drug Delivery Systems

Abstract

In this research, the development and investigation of novel nanoobjects based on biodegradable random polypeptides and synthetic non-degradable glycopolymer poly(2-deoxy-2-methacrylamido-D-glucose) were proposed as drug delivery systems. Two different approaches have been applied for preparation of such nanomaterials. The first one includes the synthesis of block-random copolymers consisting of polypeptide and glycopolymer and capable of self-assembly into polymer particles. The synthesis of copolymers was performed using sequential reversible addition-fragmentation chain transfer (RAFT) and ring-opening polymerization (ROP) techniques. Amphiphilic poly(2-deoxy-2-methacrylamido-D-glucose)-b-poly(L-lysine-co-L-phenylalanine) (PMAG-b-P(Lys-co-Phe)) copolymers were then used for preparation of self-assembled nanoparticles. Another approach for the formation of polypeptide-glycopolymer particles was based on the post-modification of preformed polypeptide particles with an oxidized glycopolymer. The conjugation of the polysaccharide on the surface of the particles was achieved by the interaction of the aldehyde groups of the oxidized glycopolymer with the amino groups of the polymer on particle surface, followed by the reduction of the formed Schiff base with sodium borohydride. A comparative study of polymer nanoparticles developed with its cationic analogues based on random P(Lys-co-D-Phe), as well as an anionic one––P(Lys-co-D-Phe) covered with heparin––was carried out. In vitro antitumor activity of novel paclitaxel-loaded PMAG-b-P(Lys-co-Phe)-based particles towards A549 (human lung carcinoma) and MCF-7 (human breast adenocarcinoma) cells was comparable to the commercially available Paclitaxel-LANS.

Amphiphilic Polypeptides Obtained by the Post-Polymerization Modification of Poly(Glutamic Acid) and Their Evaluation as Delivery Systems for Hydrophobic Drugs

“…The higher IC 50 values determined for PTX nanoformulations can be explained by the gradual accumulation of PTX in the medium due to the drug release as opposed to free PTX, whose concentration in the medium is initially defined and constant. The results obtained in this study are similar to those of the previously reported PTX delivery systems based on glycopolymers [ 31 ] or PEGylated phospholipid microparticles [ 67 ].…”

“…Due to their biocompatibility and biodegradability to non-toxic metabolites, the amphiphilic polypeptides are very promising candidates for the delivery of various drug [ 29 , 30 , 31 , 32 , 33 ]. There are a number of works devoted to the development of the polypeptide-based conjugates and nanoparticles as delivery systems for peptides [ 34 , 35 ], nucleic acids [ 36 , 37 ], cytostatic drugs [ 38 , 39 , 40 ] and some others [ 41 ].…”

Polymyxin B Conjugates with Bio-Inspired Synthetic Polymers of Different Nature

“…Here, PMX B was conjugated with P(Glu-co-Phe) and PGlu to compare the properties of physically loaded and covalently bound PMX B. In addition, two synthetic biocompatible polymers, namely poly(2-deoxy-2-methacrylamido-D-glucose) (PMAG) [30] and copolymer of vinyl succinamic acid and N-vinylsuccinimide (P(VSAA-co-VSI)) [31], were also investigated as carriers for PMX B conjugation. The composition of PMX B polymer conjugates was optimized in terms of conjugation efficacy and physicochemical characteristics of conjugates.…”

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.…”