Today, biocompatible and bioinspired well-defined copolymers with the ability to form nanoparticles are of great interest as potential drug delivery systems. In this study, we report the synthesis of novel biocompatible copolymers from monomers with different activity and capable of forming gradient copolymers by RAFT polymerization. In particular, the copolymerization of N-vinylsuccinimide (VSI) and O-cholesteryl (meth)acrylate (Ch (M)A) mediated by S,S'-dibenzyl trithiocarbonate (DBTTC) has been thoroughly studied by varying the monomer ratio and the ratio of monomer to RAFT agent. Important dependencies such as molecular weight and monomer conversion versus time, and molar fraction of monomer units as a function of monomer conversion were investigated. The obtained copolymers were thoroughly characterized using a number of physicochemical methods such as 1H NMR, 1H-13C HSQC and ATR-IR-spectroscopy, size-exclusion chromatography, static and dynamic light-scattering, as well as thermogravimetric analysis. In addition, the reactivity ratios of VSI and ChMA were determined and the dyad and triad compositions of the copolymers were calculated from the obtained values. The synthesized P(VSI-co-Ch(M)A) were subjected to selective hydrolysis of succinimide ring to convert it into succinamic acid. This approach yields a set of bioinspired amphiphilic copolymers based on Nvinylsuccinamic acid (VSAA) and Ch(M)A. The synthesized series of P(VSI-co-Ch(M)A) and P(VSAA-co-Ch(M)A) were used to obtain nanoparticles by nanoprecipitation or self-assembly via direct dissolution in aqueous medium. In addition, the method of surface hydrolysis of VSI units in pre-formed P(VSI-co-Ch(M)A) nanoparticles was applied to produce nanoparticles with hydrophilic negatively charged surface and enhanced stability. All techniques were optimized to prepare nanoparticles with characteristics suitable for systems considered for drug delivery. Successful loading of the antitumor drug irinotecan into nanoparticles was achieved with high encapsulation efficacies. The storage stability of empty and irinotecan loaded nanoparticles were studied in various media (water, saline solution, serum containing cell culture medium) under room and refrigerator conditions. The developed empty nanoparticles exhibited low rate of uptake by macrophages and low cytotoxicity to irinotecan-sensitive colon cancer cells (Caco-2). In turn, the irinotecan-loaded nanoparticles demonstrated inhibitory activity against Caco-2 cells comparable to the free drug.

N-Methyl-N-vinylacetamide–N-methyl-N-vinylamine copolymer of 85 : 15 mol

New copolymers of vinylphosphonic and p-methacrylamidobenzoic acids of varying compositions were synthesized via free radical copolymerization. The structure of the obtained polymers was confirmed by NMR and FTIR spectroscopy. As the proportion of vinylphosphonic acid in the initial reaction mixture increased, the yield of the copolymer and its molecular mass both decreased. The synthesized copolymers were found to form stable soluble luminescent complexes in dilute aqueous solutions, with a concentration range of 0.002 to 0.02 mg/ml. An increase in the concentration of vinylphosphonic acid moieties in copolymers was accompanied by a noticeable decrease in the luminescence intensity. The new copolymers' ability to bind efficiently with lanthanide ions renders them a promising material for the design of polymeric contrast agents, preparations for radioimmunotherapy and photodynamic therapy.

Radical copolymerization of coumarin with N-vinylamides (N-vinylpyrrolidone, N-vinylformamide, and N-methyl-N-vinylacetamide) initiated by 2,2′-azobisisobutyronitrile in bulk at 65°C has been studied. The comonomer reactivity ratios for the monomer pairs N-vinylformamide/coumarin (r1 = 0.22±0.03, r2 = 0) and N-methyl-N-vinylacetamide/coumarin (r1 = 0.08±0.01, r2 = 0) have been determined. Water-soluble copolymers of N-vinylamides with salts of oxycinnamic acid have been synthesized via alkaline hydrolysis of the obtained coumarin copolymers.

Cellulose is one of the main renewable polymers whose properties are very attractive in many fields, including biomedical applications. The modification of nanocrystalline cellulose (NCC) opens up the possibility of creating nanomaterials with properties of interest as well as combining them with other biomedical polymers. In this work, we proposed the covalent modification of NCC with amphiphilic polyanions such as modified heparin (Hep) and poly(αL-glutamic acid) (PGlu). The modification of NCC should overcome two drawbacks in the production of composite materials based on poly(ε-caprolactone) (PCL), namely, (1) to improve the distribution of modified NCC in the PCL matrix, and (2) to provide the composite material with osteoconductive properties. The obtained specimens of modified NCC were characterized by Fourier-transform infrared spectroscopy and solid-state 13C nuclear magnetic resonance spectroscopy, dynamic and electrophoretic light scattering, as well as thermogravimetric analysis. The morphology of PCL-based composites containing neat or modified NCC as filler was studied by optical and scanning electron microscopy. The mechanical properties of the obtained composites were examined in tensile tests. The homogeneity of filler distribution as well as the mechanical properties of the composites depended on the method of NCC modification and the amount of attached polyanion. In vitro biological evaluation showed improved adhesion of human fetal mesenchymal stem cells (FetMSCs) and human osteoblast-like cells (MG-63 osteosarcoma cell line) to PCL-based composites filled with NCC bearing Hep or PGlu derivatives compared to pure PCL. Furthermore, these composites demonstrated the osteoconductive properties in the experiment on the osteogenic differentiation of FetMSCs.

Water-soluble copolymers of p-methacrylamidobenzoic acid (MABA) with neutral comonomers ( N -vinylpyrrolidone (VP), N -methyl- N -vinylacetamide (MVAA), N -methacryloyl glucosamine (MAG)) and anionic comononer sodium styrene sulfonate (NaSS) were synthesized by radical copolymerization. The interactions between the prepared copolymers and Tb 3+ ions in aqueous solutions were studied; the significant influence of chemical structure of a comonomer on luminescence intensity of Tb 3+ complexes with the copolymers was revealed. The luminescence intensity of Tb 3+ complexes with the copolymers containing N -vinylamide units (VP, MVAA) is three times more intense than that observed for the complexes between Tb 3+ and MAG-containing copolymers. In the case of NaSS-containing copolymers, the luminescence intensity is controlled by the values of binding constants between Tb 3+ and MABA and the content of MABA units in a copolymer. The studied copolymers and their complexes with Tb 3+ have low cytotoxicity and a pronounced antiviral activity against human respiratory syncytial virus.

Polymeric hydrogels based on sulfo-containing comonomers are promising materials for biotechnological application, namely, for use as a system for delivering water and minerals during seed germination in conditions of an unstable moisture zone. In this work, cryogels based on 3-sulfopropyl methacrylate and 2-hydroxyethyl methacrylate copolymers were obtained by the cryotropic gelation method. The morphology, specific surface area, and swelling behaviors of cryogels are found to depend on the total concentration of monomers in the reaction system and the content of the gel fraction in cryogels. Cryogels formed in the presence of nanodiamonds are shown to exhibit high biological activity during the germination of Lepidium sativum L. variety Ajur seeds, which manifests itself by stimulating seed germination and a significant increase in the raw weight of sprouts. These results indicate that sulfonic cryogels have a high potential to improve seed germination and plant growth, proving that such cryogels can be used as environmentally friendly materials for agricultural applications.

The growth of microbial multidrug resistance is a problem in modern clinical medicine. Chemical modification of active pharmaceutical ingredients is an attractive strategy to improve their biopharmaceutical properties by increasing bioavailability and reducing drug toxicity. Conjugation of antimicrobial drugs with natural polysaccharides provides high efficiency of these systems due to targeted delivery, controlled drug release and reduced toxicity. This paper reports a two-step synthesis of colistin conjugates (CT) with succinyl chitosan (SucCS); first, we modified chitosan with succinyl anhydride to introduce a carboxyl function into the polymer molecule, which was then used for chemical grafting with amino groups of the peptide antibiotic CT using carbodiimide chemistry. The resulting polymeric delivery systems had a degree of substitution (DS) by CT of 3–8%, with conjugation efficiencies ranging from 54 to 100% and CT contents ranging from 130–318 μg/mg. The size of the obtained particles was 100–200 nm, and the ζ-potential varied from −22 to −28 mV. In vitro release studies at pH 7.4 demonstrated ultra-slow hydrolysis of amide bonds, with a CT release of 0.1–0.5% after 12 h; at pH 5.2, the hydrolysis rate slightly increased; however, it remained extremely low (1.5% of CT was released after 12 h). The antimicrobial activity of the conjugates depended on the DS. At DS 8%, the minimum inhibitory concentration (MIC) of the conjugate was equal to the MIC of native CT (1 µg/mL); at DS of 3 and 5%, the MIC increased 8-fold. In addition, the developed systems reduced CT nephrotoxicity by 20–60%; they also demonstrated the ability to reduce bacterial lipopolysaccharide-induced inflammation in vitro. Thus, these promising CT-SucCS conjugates are prospective for developing safe and effective nanoantibiotics.

Type I interferons, particularly IFNα-2b, play essential roles in eliciting adaptive and innate immune responses, being implicated in the pathogenesis of various diseases, including cancer, and autoimmune and infectious diseases. Therefore, the development of a highly sensitive platform for analysis of either IFNα-2b or anti-IFNα-2b antibodies is of high importance to improve the diagnosis of various pathologies associated with the IFNα-2b disbalance. For evaluation of the anti-IFNα-2b antibody level, we have synthesized superparamagnetic iron oxide nanoparticles (SPIONs) coupled with the recombinant human IFNα-2b protein (SPIONs@IFNα-2b). Employing a magnetic relaxation switching assay (MRSw)-based nanosensor, we detected picomolar concentrations (0.36 pg/mL) of anti-INFα-2b antibodies. The high sensitivity of the real-time antibodies' detection was ensured by the specificity of immune responses and the maintenance of resonance conditions for water spins by choosing a high-frequency filling of short radio-frequency pulses of the generator. The formation of a complex of the SPIONs@IFNα-2b nanoparticles with the anti-INFα-2b antibodies led to a cascade process of the formation of nanoparticle clusters, which was further enhanced by exposure to a strong (7.1 T) homogenous magnetic field. Obtained magnetic conjugates exhibited high negative MR contrast-enhancing properties (as shown by NMR studies) that were also preserved when particles were administered in vivo. Thus, we observed a 1.2-fold decrease of the T2 relaxation time in the liver following administration of magnetic conjugates as compared to the control. In conclusion, the developed MRSw assay based on SPIONs@IFNα-2b nanoparticles represents an alternative immunological probe for the estimation of anti-IFNα-2b antibodies that could be further employed in clinical studies.

Conducting polymer polyelectrolyte microspheres are typically composed of a cationic conducting polymer and an anionic polymer. The polymer chains inside these microspheres are physically or chemically cross-linked, creating a network that enables high water retention. Poly(3,4-ethylenedioxythiophene) (PEDOT) being an electrically conductive polymer exhibits a high conductivity and has great biotechnological applications. The unique combination of properties of PEDOT containing polyelectrolyte microspheres makes them widely investigated materials for electroresponsive cells, tissue engineering, and bio-sensors. The demand to produce PEDOT with varied properties depending the specific application requires the understanding of the basic principles of template formation. In the present work, we studied the inverse suspension polymerization of p-styrenesulfonic acid in the presence of a cross-linking agent as a synthetic way for the formation of porous polyelectrolyte microspheres. We traced how the nature of the emulsifier affected both the structure of the surface layer of the microspheres and the degree of their cross-linking. The porous structure of polyelectrolyte microspheres obtained is found to promote the polymerization of EDOT in their presence throughout the entire microsphere volume. The structural characteristics of the polyelectrolyte/PEDOT complexes in relation to their electrochemical properties have been studied.

The development of nanotechnology-based antibiotic delivery systems (nanoantibiotics) is an important challenge in the effort to combat microbial multidrug resistance. These systems have improved biopharmaceutical characteristics by increasing local bioavailability and reducing systemic toxicity and the number and frequency of drug side effects. Conjugation of low -molecular -weight antibacterial agents with natural polysaccharides is an effective strategy for developing optimal targeted delivery systems with programmed release and reduced cytotoxicity. This study describes the synthesis of conjugates of colistin (CT) and hyaluronic acid (HA) using carbodiimide chemistry to conjugate the amino groups of CT with the carboxyl groups of HA. The obtained polysaccharide carriers had a degree of substitution (DS) with CT molecules of 3-10 %, and the CT content was 129-377 μg/mg. The size of the fabricated particles was 300-600 nm; in addition, there were conjugates in the form of single macromolecules (30-50 nm). The ζ-potential of developed systems was about -20 mV. In vitro release studies at pH 7.4 and pH 5.2 showed slow hydrolysis of amide bonds, with a CT release of 1-5 % after 24 h. The conjugates retained antimicrobial activity depending on the DS: at DS 8 %, the minimum inhibitory concentration (MIC) of the conjugate corresponded to the MIC of free CT. The resulting systems also reduced CT nephrotoxicity by 20-50 %. These new conjugates of CT with HA are promising for the development of nanodrugs for safe and effective antimicrobial therapy.

Free radical copolymerization is used for the synthesis of novel water-soluble copolymers of vinylphosphonic acid with 2-deoxy-2-methacrylamido-D-glucose or 4-acryloylmorpholine, with varied compositions and molecular masses, as well as for the synthesis of copolymers of vinylphosphonic acid with acrylamide. The obtained copolymers contain 6–97 mol.% of vinylphosphonic acid units, and their molecular masses vary from 5 × 103 to 310 × 103. The monomer reactivity ratios of vinylphosphonic acid and 2-deoxy-2-methacrylamido-D-glucose in copolymerization are determined for the first time, and their values are 0.04 and 9.02, correspondingly. It is demonstrated that the synthesized copolymers form luminescent mixed-ligand complexes with Eu3+, thenoyltrifluoroacetone, and phenanthroline. The influence of the comonomer’s nature on the intensity of the luminescence of complex solutions is revealed.

Boron neutron capture therapy (BNCT) has been recognized as a very promising approach for cancer treatment. In the case of osteosarcoma, boron-containing scaffolds can be a powerful tool to combine boron delivery to the tumor cells and the repair of postoperative bone defects. Here we describe the fabrication and characterization of novel biodegradable polymer composites as films and 3D-printed matrices based on aliphatic polyesters containing closo-borates (CB) for BNCT. Different approaches to the fabrication of composites have been applied, and the mechanical properties of these composites, kinetics of their degradation, and the release of closo-borate have been studied. The most complex scaffold was a 3D-printed poly(ε-caprolactone) matrix filled with CB-containing alginate/gelatin hydrogel to enhance biocompatibility. The results obtained allowed us to confirm the high potential of the developed composite materials for application in BNCT and bone tissue regeneration.

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.

Conductive hydrogels are polymeric materials that are promising for bioelectronic applications. In the present study, a complex based on sulfonic cryogels and poly(3,4-ethylenedioxythiophene) (PEDOT) was investigated as an example of a conductive hydrogel. Preparation of polyacrylate cryogels of various morphologies was carried out by cryotropic gelation of 3-sulfopropyl methacrylate and sulfobetaine methacrylate in the presence of functional comonomers (2-hydroxyethyl methacrylate and vinyl acetate). Polymerization of 3,4-ethylenedioxythiophene in the presence of several of the above cryogels occurred throughout the entire volume of each polyelectrolyte cryogel because of its porous structure. Structural features of cryogel@PEDOT complexes in relation to their electrochemical properties were investigated. It was shown that poly(3,4-ethylenedioxythiophene) of a linear conformation was formed in the presence of a cryogel based on sulfobetaine methacrylate, while minimum values of charge-transfer resistance were observed in those complexes, and electrochemical properties of the complexes did not depend on diffusion processes.

Cellulose nanofibers (CNF) produced by bacterial were functionalized along the surface with 3-(trimethoxysilyl)propyl methacrylate (TMSPM). The chemical and crystalline structure of the material was confirmed with NMR, FTIR, EDX and XRD methods. Modified CNF were used as a crosslinker and reinforcer for polymerizable deep eutectic solvent (DES) based on acrylic acid and choline chloride. Dispersions of modified nanofibers in DES were applied as UV-curable ink for 3D printing. It was shown that shielding of -OH groups of the cellulose surface with TMSPM increased the quality of 3D printed filaments due to reduced CNF agglomeration. At the same time, surface methacrylic groups copolymerize with acrylic acid forming crosslinked ion gel. Elastic moduli of the prepared ion gels were identical to those of gels based on unmodified CNF and crosslinked with N,N'-methylenebisacrylamide. However, strength and the ultimate elongation of the material prepared in this work were 1.05 ± 0.08 MPa at 2700% that is significantly higher than those of the material prepared with unmodified CNF.

Radical polymerization was used to synthesize and characterize (co)polymers with sodium styrenesulfonate (NaSS), 4-methacryloylamidosalicylic acid (MASA), and N-vinylpyrrolidone, which have a low cytotoxicity and a high antiviral activity against the human respiratory syncytial virus. The interaction of copolymers with Tb3+ ions was studied. The complexes formed in dilute aqueous solutions at a concentration of MASA units c ⩽ 1 · 10−4 mol L−1 demonstrate a strong luminescence. The luminescence intensity is independent of copolymer composition, but increases when the NaSS units are substituted with uncharged N-vinylpyrrolidone units. The obtained Tb3+ polymer complexes are promising luminescent sensors for the visualization of biological objects interacting with copolymers.

Nanotechnology-based modification of known antimicrobial agents is a rational and straightforward way to improve their safety and effectiveness. The aim of this study was to develop colistin (CT)-loaded polymeric carriers based on hyaluronic acid (HA) for potential application as antimicrobial agents against multi-resistant gram-negative microorganisms (including ESKAPE pathogens). CT-containing particles were obtained via a polyelectrolyte interaction between protonated CT amino groups and HA carboxyl groups (the CT-HA complex formation constant [log(CT-)(HA)] was about 5.0). The resulting polyelectrolyte complexes had a size of 210-250 nm and a negative charge (zeta-potential -19 mV), with encapsulation and loading efficiencies of 100% and 20%, respectively. The developed CT delivery systems were characterized by modified release (45% and 85% of CT released in 15 and 60 min, respectively) compared to pure CT (100% CT released in 15 min). In vitro tests showed that the encapsulation of CT in polymer particles did not reduce its pharmacological activity; the minimum inhibitory concentrations of both encapsulated CT and pure CT were 1 mu g/mL (against Pseudomonas aeruginosa).

New copolymers of 2-methacryloyloxyethyl phosphorylcholine with 2-Deoxy-2-methacrylamido-D-glucose, N-vinylpyrrolidone, and N-vinyl-N-methylacetamide were synthesized and characterized; the obtained copolymers contained 10-50 mol% of phosphorylcholine moieties, and their molecular masses ranged from 1.05 x 10(5) to 4.40 x 10(5). Reactivity ratios of the monomers were estimated. Conformational states of the copolymers in aqueous solutions were studied. The synthesized copolymer was grafted onto the surface of carbon fiber biosorbent using gamma-radiation.