Poly(lactic acid) and Nanocrystalline Cellulose Methacrylated Particles for Preparation of Cryogelated and 3D-Printed Scaffolds for Tissue Engineering

Different parts of bones possess different properties, such as the capacity for remodeling cell content, porosity, and protein composition. For various traumatic or surgical tissue defects, the application of tissue-engineered constructs seems to be a promising strategy. Despite significant research efforts, such constructs are still rarely available in the clinic. One of the reasons is the lack of resorbable materials, whose properties can be adjusted according to the intended tissue or tissue contacts. Here, we present our first results on the development of a toolbox, by which the scaffolds with easily tunable mechanical and biological properties could be prepared. Biodegradable poly(lactic acid) and nanocrystalline cellulose methacrylated particles were obtained, characterized, and used for preparation of three-dimensional scaffolds via cryogelation and 3D printing approaches. The composition of particles-based ink for 3D printing was optimized in order to allow formation of stable materials. Both the modified-particle cytotoxicity and the matrix-supported cell adhesion were evaluated and visualized in order to confirm the perspectives of materials application

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

In this research, the development and investigation of novel nanoobjects based on biodegradable random polypeptides and synthetic non-degradable glycopolymer poly(2-deoxy-2-meth-acrylamido-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(Lysco-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 for VEGF siRNA Delivery into Retinal Epithelial Cells

Polyethyleneimine, poly-L-lysine, chitosan and some others cationic polymers have been thoroughly studied as nucleic acid delivery systems in gene therapy. However, the drug release from these systems proceeds at a very low rate due to extremely high binding between a carrier and gene material. To reduce these interactions and to enhance drug release, we developed a set of amphiphilic polypeptides containing positively and negatively charged amino acids as well as a hydrophobic one. The copolymers obtained were characterized by size-exclusion chromatography, static light scattering, HPLC amino acid analysis and (HNMR)-H-1 spectroscopy. All copolymers formed particles due to a self-assembly in aqueous media. Depending on polypeptide composition, the formation of particles with hydrodynamic diameters from 180 to 900 nm was observed. Stability of polymer particles, loading and release efficiency were carefully studied. Cellular uptake of the particles was efficient and their cytotoxicity was negligible. The application of polymer carriers, containing siRNA, to vascular endothelial growth factor (VEGF-A165) silencing of ARPE-19 cells was successful. The gene silencing was confirmed by suppression of both messenger RNA and protein expression.Peer reviewe

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

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

Polypeptide self-assembled nanoparticles as delivery systems for polymyxins B and E

Polymyxins are peptide antibiotics that are highly efficient against many multidrug resistant pathogens. However, the poor stability of polymyxins in the bloodstream requires the administration of high drug doses that, in turn, can lead to polymyxin toxicity. Consequently, different delivery systems have been considered for polymyxins to overcome these obstacles. In this work, we report the development of polymyxin delivery systems based on nanoparticles obtained from the self-assembly of amphiphilic random poly(L-glutamic acid-co-D-phenylalanine). These P(Glu-co-DPhe) nanoparticles were characterized in terms of their size, surface charge, stability, cytotoxicity, and uptake by macrophages. The encapsulation efficiency and drug loading into P(Glu-co-DPhe) nanoparticles were determined for both polymyxin B and E. The release kinetics of polymyxins B and E from nanoformulations was studied and compared in buffer solution and human blood plasma. The release mechanisms were analyzed using a number of mathematical models. The minimal inhibitory concentrations of the nanoformulations were established and compared with those determined for the free antibiotics. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Preface to “Advances in Bio-Based and Biodegradable Polymeric Composites”

The use of polymers for various purposes is increasing every year [...

Modification of Cellulose Micro- and Nanomaterials to Improve Properties of Aliphatic Polyesters/Cellulose Composites: A Review

Aliphatic polyesters/cellulose composites have attracted a lot attention due to the perspectives of their application in biomedicine and the production of disposable materials, food packaging, etc. Both aliphatic polyesters and cellulose are biocompatible and biodegradable polymers, which makes them highly promising for the production of “green” composite materials. However, the main challenge in obtaining composites with favorable properties is the poor compatibility of these polymers. Unlike cellulose, which is very hydrophilic, aliphatic polyesters exhibit strong hydrophobic properties. In recent times, the modification of cellulose micro- and nanomaterials is widely considered as a tool to enhance interfacial biocompatibility with aliphatic polyesters and, consequently, improve the properties of composites. This review summarizes the main types and properties of cellulose micro- and nanomaterials as well as aliphatic polyesters used to produce composites with cellulose. In addition, the methods for noncovalent and covalent modification of cellulose materials with small molecules, polymers and nanoparticles have been comprehensively overviewed and discussed. Composite fabrication techniques, as well as the effect of cellulose modification on the mechanical and thermal properties, rate of degradation, and biological compatibility have been also analyzed

Macroporous Polymer Monoliths in Thin Layer Format

Nowadays, macroporous polymer monoliths represent widely used stationary phases for a number of dynamic interphase mass exchange processes such as high-performance liquid chromatography, gas chromatography, electrochromatography, solid-phase extraction, and flow-through solid-state biocatalysis. This review represents the first summary in the field of current achievements on the preparation of macroporous polymer monolithic layers, as well as their application as solid phases for thin-layer chromatography and different kinds of microarray

Nanomedicines Bearing an Alkylating Cytostatic Drug from the Group of 1,3,5-Triazine Derivatives: Development and Characterization

Cancer is still one of the major diseases worldwide. The discovery of new drugs and the improvement of existing ones is one of the areas of priority in the fight against cancer. Dioxadet ([5-[[4,6-bis(aziridin-1-yl)-1,3,5-triazin-2-yl]amino]-2,2-dimethyl-1,3-dioxan-5-yl]methanol) represents one of the promising 1,3,5-triazine derivatives and has cytostatic activity towards ovarian cancer. In this study, we first report the development of dioxadet-bearing nanomedicines based on block-copolymers of poly(ethylene glycol) monomethyl ether (mPEG) and poly(D,L-lactic acid) (PLA)/poly(ε-caprolactone) (PCL) and then conduct an investigation into their characteristics and properties. The preparation of narrow-sized nanoparticles with a hydrodynamic diameter of 100–120 nm was optimized using a nanoprecipitation approach. Thoughtful optimization of the preparation of nanomedicines was carried out through adjustments to the polymer’s molecular weight, the pH of the aqueous medium used for nanoprecipitation, the initial drug amount in respect to the polymer, and polymer concentration in the organic phase. Under optimized conditions, spherical-shaped nanomedicines with a hydrodynamic diameter of up to 230 nm (PDI b-PLA and mPEG-b-PCL, respectively. Deep analysis of the release mechanisms was carried out with the use of a number of mathematical models. The developed nanoparticles were non-toxic towards both normal (CHO-K1) and cancer (A2780 and SK-OV-3) ovarian cells. A cell cycle study revealed lesser toxicity of nanomedicines towards normal cells and increased toxicity towards cancer cells. The IC50 values determined for dioxadet nanoformulations were in the range of 0.47–4.98 μg/mL for cancer cells, which is close to the free drug’s efficacy (2.60–4.14 μg/mL). The highest cytotoxic effect was found for dioxadet loaded to mPEG-b-PCL nanoparticles

Poly(lactic acid) and Nanocrystalline Cellulose Methacrylated Particles for Preparation of Cryogelated and 3D-Printed Scaffolds for Tissue Engineering

Different parts of bones possess different properties, such as the capacity for remodeling cell content, porosity, and protein composition. For various traumatic or surgical tissue defects, the application of tissue-engineered constructs seems to be a promising strategy. Despite significant research efforts, such constructs are still rarely available in the clinic. One of the reasons is the lack of resorbable materials, whose properties can be adjusted according to the intended tissue or tissue contacts. Here, we present our first results on the development of a toolbox, by which the scaffolds with easily tunable mechanical and biological properties could be prepared. Biodegradable poly(lactic acid) and nanocrystalline cellulose methacrylated particles were obtained, characterized, and used for preparation of three-dimensional scaffolds via cryogelation and 3D printing approaches. The composition of particles-based ink for 3D printing was optimized in order to allow formation of stable materials. Both the modified-particle cytotoxicity and the matrix-supported cell adhesion were evaluated and visualized in order to confirm the perspectives of materials application