Search

Abstract: Aim of this paper was that to prepare biocompatible, polyaspartamide based copolymers containing spermine or spermine/hydrophobic side chains able to condense nucleic acids and to transfect mammalian cells. Copolymers were prepared starting from α,β-poly-(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) and exploiting the reactive hydroxyl groups in the polymeric side chains by subsequent activation reactions to obtain PHEA-Spermine (PHEA-Spm) and PHEA-Spermine-Butyramide (PHEA-Spm-C4). Molecular, physico-chemical and biological characterization of copolymers and interpolyelectrolyte complexes with plasmid DNA was performed. Experimental results evidenced that these copolymers are able to form complexes with plasmid DNA already at low polycation/DNA weight ratio ranging from 0.75/1 to 2/1. Interpolyelectrolyte complexes with decreased size were obtained when increasing the polycation/DNA weight ratio, until nanosized dimensions were reached. Copolymers as well as complexes were not haemolytic and non toxic in vitro. In vitro cell transfection with PHEA derivatives showed good biocompatibility and high transfection efficiency (luciferase) in cancer cells in comparison with commercially available, but toxic transfection agents. [Copyright &y& Elsevier]

Abstract: The formation of a novel interpolyelectrolyte complex (IPEC) between basic butylated methacrylate copolymer and kappa-carrageenan was investigated and the product formed was characterized. Turbidity measurements and elemental analyses pointed to a 1:1 interaction of the repeating units. These results and FT-IR confirmed IPEC formation. Electronic microscopy images, particle size determination by image analysis and N2 (77K) adsorption measurements were consistent with a porous material. This IPEC formed presented very good flowability and compactibility. Two maxima were observed in the swelling behaviour as a function of pH. The performance of the IPEC as a matrix for controlled release of drugs was evaluated, using ibuprofen as a model drug. Release profiles were properly represented by a mathematical model, which indicates that the system releases ibuprofen in a zero-order manner. These profiles could be controlled by conveniently modifying the proportion of the IPEC in the tablets. [Copyright &y& Elsevier]

Abstract: Static/structural characteristics of non-covalent complexes, formed by terminally charged hyperbranched polymers and oppositely charged neutralizing linear polyelectrolytes, are examined by means of Brownian dynamics computer simulations. Excluded-volume, electrostatic and hydrodynamic interactions are taken into account in implicit solvent. Three pairs of complexes consisting of linear chains and hyperbranched molecules each bearing different molecular weight and distinctly diverse topologies are examined under conditions of varying electrostatic interactions. The findings from the present work demonstrate that through an appropriate modification of internal structure and external stimuli, key attributes of such complexes like size, shape and local density distribution, can be tuned at desired levels, rendering them promising candidates for a wide range of pertinent nanoscale applications. [Copyright &y& Elsevier]

Abstract: Controlled/‘living’ radical polymerization methods, including the versatile reversible addition–fragmentation chain transfer (RAFT) polymerization process, are rapidly moving to the forefront in construction of drug and gene delivery vehicles. The RAFT technique allows an unprecedented latitude in the synthesis of water soluble or amphiphilic architectures with precise dimensions and appropriate functionality for attachment and targeted delivery of diagnostic and therapeutic agents. This review focuses on the chemistry of the RAFT process and its potential for preparing well-defined block copolymers and conjugates capable of stimuli-responsive assembly and release of bioactive agents in the physiological environment. Recent examples of block copolymers with designed structures and segmental compositions responsive to changes in pH or temperature are reviewed and hurdles facing further development of these novel systems are discussed. [Copyright &y& Elsevier]

Artificial polymeric carriers for bioactive compounds, such as drugs and genes, are increasingly being reported in the literature. Most are poly- electrolytes aimed at being injected into body fluids that are composed of charged macromolecules (proteins, glycoproteins, poly(glycosamino glycane)s, polynucleotides, etc.). Many interactions can occur and lead to dramatic phenomena, such as polyelectrolyte complexation or substitution, cell aggregation and hemolysis. For the purpose of modeling and better understanding these interactions and their effects, a library of polyanions of the poly(L-lysine citramide)-type was interacted with the polycation poly(L-lysine) in aqueous media. Different fractions of complexes were generated by successive additions of aliquots of the polycation solution to the polyanion library solution by a titrating process. The two components, the polycation and the complex population of polyanions, were separated from the collected complex fractions by affinity chro- matography and then analyzed by aqueous SEC. Molecular weight selectivity was shown, the high molecular weight polyanion macromolecules precipitated first, while complexes involving smaller molecules were found to remain in solution. The data show the potential of affinity chromatography for studying inter-polyelectrolyte complexes and emphasizes the critical role that polydispersity can play when therapeutic charged macromolecules are injected into blood. [ABSTRACT FROM AUTHOR]

The micellization of ionic amphiphilic diblock copolymers, polyisobutylene-block-poly(methacrylic acid) (PIB-b-PMAA), with a constant degree of polymerization of the non-ionic block (DPn=20) and various degrees of polymerization of the polyelectrolyte block (DPn=100–425) was examined in aqueous media by means of fluorescence spectroscopy using pyrene as a polarity probe. The molar values of the critical micellization concentration (cmc) were found to be around 2×10−6 mol/l, being nearly independent of the length of the polyelectrolyte block as well as pH (in the range 6–9) and ionic strength (≤0.5 M NaCl) while the specific cmc values varied from 20 to 100 mg/l. Small-angle neutron scattering (SANS) and dynamic light scattering (DLS) experiments provided evidence that aggregation numbers and hydrodynamic radii of the formed copolymer micelles are sensitive to variations of pH and ionic strength, indicating that these micelles might be ‘dynamic’ rather than ‘frozen’ ones. It was also shown by means of a combination of turbidimetry, analytical ultracentrifugation, fluorescence spectroscopy, SANS, and DLS that the formed copolymer micelles mixed with a strong cationic polyelectrolyte, poly(N-ethyl-4-vinylpyridinium bromide) at charge ratio Z=[+]/[−] not exceeding a certain critical value ZM<1, generate peculiar water-soluble micellar complex onion-like species, each containing a two-phase hydrophobic nucleus and a hydrophilic corona. The nucleus consists of a PIB core and a shell assembled from the fragments of water-insoluble interpolyelectrolyte complex. The corona is formed by the excess fragments of poly(sodium methacrylate) blocks not involved in complexation with poly(N-ethyl-4-vinylpyridinium bromide). [Copyright &y& Elsevier]

Interactions of a major whey protein, β-lactoglobulin (BLG), with an anionic polysaccharide, dextran sulfate (DS), were investigated by nephelometric titration and high-sensitivity differential scanning calorimetry at pH 2.5–7.0 and NaCl concentrations of 0–500 mM. The pH-dependences of the light scattering of the BLG−DS system revealed a maximum. Its position was dependent on the polysaccharide/protein ratio and salt concentration. Thermodynamic parameters of the denaturation of BLG in mixtures with DS were determined at different pH and salt concentrations. Conformational stability of BLG in the BLG–DS complexes was shown to either increase or decrease depending on the solution conditions and complex composition. The binding curves of BLG to DS were calculated from the light scattering and calorimetric data and analyzed using various binding models including the Langmuir and McGhee–von Hippel models as well as a stoichiometric interpolyelectrolyte reaction. Mechanisms responsible for changes in the BLG oligomer structure and conformational stability induced by the complex formation with the polysaccharide were proposed. [Display omitted] • BLG–DS complexes form at pH 3.0–pI BLG and NaCl concentration up to 0.5 M. • The complex formation can result in the dissociation of BLG dimer. • Stability of BLG is defined by charge-charge or charge-dipole interactions with DS. • Stoichiometric BLG–DS complexes are formed at high ionic strength. [ABSTRACT FROM AUTHOR]

• Benznidazole-loaded multiparticulate drug delivery systems (BZ-MDDS) were in vivo studied. • BZ-MDDS showed trypanocidal efficacy at conventional or low doses of BZ. • BZ-MDDS reduced heart and liver injury, increasing Chagas disease treatment safety. • BZ-MDDS exhibited an improved preclinical performance for Chagas disease treatment. Benznidazole (BZ) is a first-line drug for the treatment of Chagas disease; however, it presents several disadvantages that could hamper its therapeutic success. Multiparticulate drug delivery systems (MDDS) are promising carriers to improve the performance of drugs. We developed BZ-loaded MDDS intended for improving Chagas disease therapy. To assess their efficacy and safety, Trypanosoma (T) cruzi infected BALB/c mice were orally treated with free BZ or BZ-MDDS at different regimens (doses of 50 and 100 mg/kg/day, administered daily or at 2- or 5-days intervals) and compared with infected non-treated (INT) mice. At 100 mg/kg/day, independent of the administration regimen, both treatments were able to override the parasitemia, and at 50 mg/kg/day significantly reduced it compared to INT mice. BZ-MDDS at a dose of 100 mg/kg/day administered every 5 days (BZ-MDDS 100–13d) induced the lowest cardiac parasite load, indicating an improved efficacy with lower total dose of BZ when loaded to the MDDS. Reactive oxygen species produced by leukocytes were higher in INT and mice treated with BZ at 50 mg/kg/day compared to 100 mg/kg/day, likely because of persistent infection. BZ-MDDS treatments markedly reduced heart and liver injury markers compared to INT mice and those receiving the standard treatment. Therefore, BZ-MDDS exhibited enhanced activity against T. cruzi infection even at lower doses and reduced administration frequency compared to free BZ while increasing the treatment safety. They likely avoid undesired side effects of BZ by keeping a sustained concentration, avoiding plasmatic drug peaks. BZ-MDDS evidenced significant improvements in experimental Chagas disease treatment and can be considered as a potential improved therapeutic alternative against this illness. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] In this study, volatile perfume was encapsulated in microcapsules (MCs) via interpolyelectrolyte complexes (IPECs) of oppositely charged polymers, with high encapsulation efficiency, to be delivered in a sustained manner. Positively charged chitosan (CTS) and negatively charged Eudragit® S100 (ES100) were used as eco-friendly biopolymers. Limonene (LMN) was selected as the model perfume. First, the solution of LMN in ethyl acetate and poloxamer 407 (POX407) in acidic solution was emulsified using ultrasonication. CTS and ES100 were added in that particular order to form o/w emulsion. LMN-loaded microcapsules (LMN-MCs) were prepared by adjusting the pH and freeze-drying for solidification. The electrostatic interactions of CTS and ES100 to form IPECs were highly dependent on pH, changing in the microscopic images of emulsion droplets and zeta potential. The NH 3 + group of CTS and the COO– group of ES100 caused the electrostatic interactions at a specific pH. The formation mechanism of LMN-MCs was successfully validated using instrumental analysis, charge density, and energy dispersive X-ray spectrometer (EDS) mapping. Encapsulation efficiency, loading content, and release rates of LMN-MCs varied according to the ratios of CTS and ES100, demonstrating optimal performance at a 1:1 ratio. The current LMN-MCs could provide a simple manufacturing process with high performance in terms of encapsulation efficiency (>94%), drug loading, yield and sustained release of volatile perfume for 120 h. [ABSTRACT FROM AUTHOR]

The formation of interpolyelectrolyte complexes (IPEC) between Eudragit EPO (EPO) and Carbomer 940 (C940) was investigated with a view to their use in peroral controlled-release drug delivery systems. The structure of the synthesized products was investigated using FTIR spectroscopy and MT-DSC methods, which indicated that the synthesized product can be considered to be an IPEC stabilized by a cooperative system of ionic bonds. Based on results of capillary viscosimetry and elemental analysis, the IPEC prepared at pH 4.0 has a characteristic composition with a C940:EPO mole ratio of 1.75:1. [ABSTRACT FROM AUTHOR]

Magnetic compounds, based on magnetite nanoparticles and interpolyelectrolyte complexes (IPEC) were prepared from chitosan (CS) and poly(sodium 4-styrenesulfate) (NaPSS). Two types of composite were obtained: one with positive surface charge and another one with negatively charged surface. The composites were used to adsorb a cationic drug (tetracycline hydrochloride, HTCCl) and an anionic one (sodium cromoglycate, NaCG). Sorption occurred in the form of multiple layers, tending to a saturation value (following Sips isotherm), with saturation sorption concentrations of ca. 0.2 mmol of drug per gram of composite for HTCCl on both positively and negatively charged composites, probably due to the protonation of chitosan by HTCCl. In the case of the anionic drug, it was adsorbed with the same intensity on the composite of opposite charge, while for the composite with negative charge saturation occurred at a value of ca. 0.05 mol per gram of composite. Gibbs free energy of adsorption for dilute solution conditions was estimated, ranging from ‒17 to −3 kJ/mol, and the analysis of thermal degradation kinetics of composites, using the isoconversional approach, indicated that magnetite decreased apparent energy of activation (with values reaching 400 kJ/mol) for the degradation of the organic phase. [ABSTRACT FROM AUTHOR]

• An anionic cross-linked copolymer forms microgel particles after swelling in water. • Reaction of microgel with a linear polycation results in stable aqueous formulation. • Being applied to soil, the formulations give mechanically stable polymer-soil crusts. • Soil, associated with microgels, demonstrates a high water retention capacity. • Microgels are promising for preparing anti-erosion and water-saving formulations. In this article we describe the use of novel aqueous polymer formulations for stabilization of sand and soil against wind erosion and retention of water in polymer-treated sand/soil samples. Two series of formulations were prepared. The first consisted of polyacrylic acid (PAA) and two electrostatic complexes of PAA with cationic poly(diallyldimethylammonium chloride): negatively and positively charge; the second included PAA-based cross-linked copolymer (PAA#) which forms microgel particles upon swelling and two its electrostatic complexes with the polycation: negatively and positively charged. 1 mass% formulations showed the stability against aggregation for 3 months excepting the negative complex with PAA which aggregated within half an hour after preparation. The viscosity of 1 mass% formulations, which lies within a (1.6÷320)×10−6 m2/s interval, allowed their deposition over fine-grained sand and loamy sand soil using a conventional spray machine followed by formation of polymer-sand(soil) crusts. Both for sand and soil, the PAA#-based crusts demonstrated a higher resistance to mxechanical loads in comparison with the crusts formed by linear PAA: up to a 42.5 MPa mechanical strength for sand/PAA# crust against a 12.5 MPa strength for sand/PAA crust. Additionally, the PAA#-based crusts was not impacted by airstream, up to a 190 km per hour air speed, while PAA-based crust was destroyed within a minute. Finally, PAA# alone and its negative complex were characterized by a high swelling (degree of swelling up to 195) that allowed them to maintain a high water retention capacity, being bound to sand and soil. The results are promising for preparing anti-erosion and water-saving formulations, especially in areas with insufficient moisture content, and design of sand-based composite materials. [ABSTRACT FROM AUTHOR]

• Nanocomposites were obtained by thermochemical reduction of Ag+ at 150 °C for 30 min. • The least average size of silver nanoparticles is 4.7 nm for pectin––Ag–chitosan+. • The greatest average size of silver nanoparticles is 9 nm for starch––Ag–starch+. • The greatest antimicrobial activity is the pectin––Ag–chitosan+, and the least starch––Ag–starch+. The effect of the chemical structure of interpolyelectrolyte complexes (IPEC) based on polymers of natural origin (pectin––chitosan+, pectin––cationic starch (starch+), carboxymethylcellulose (CMC–)–cationic β-cyclodextrin (β-CD+), anionic starch (starch–)–cationic starch (starch+) on the structure, morphology, thermomechanical and antimicrobial properties of silver-containing nanocomposites obtained by thermochemical reduction of Ag+ ions in interpolyelectrolyte-metal complexes (IMC) was studied. Thermochemical reduction of Ag+ ions in the IMC bulk for 30 min at 150 °C led to formation of silver-containing nanocomposites and this fact was confirmed by wide-angle X-ray scattering method. Transmission electron microscopy showed that different sized of silver nanoparticles were formed depending on the chemical structure of IPEC. The average size of silver nanoparticles was found to be 4.7 nm for pectin––Ag–chitosan+; 5.3 nm for pectin––Ag–starch+; 6.3 for CMC––Ag–β-CD+ and 9 nm for starch––Ag–starch+, correspondingly. The nanocomposites having smaller average nanoparticle size exhibited higher antimicrobial activity against S. aureus and E. coli strains. Pectin––Ag–chitosan+ nanocomposites formed by thermochemical reduction of Ag+ ions showed that the diameter of the inhibition zone against S. aureus and E. coli strains was 19.7 and 32.6 mm, respectively, whereas these values were 15.6 and 14 mm, respectively, for the same nanocomposites obtained by chemical reduction using ascorbic acid. [ABSTRACT FROM AUTHOR]

By means of computer simulation and analytical theory, we first demonstrated that the interpolyelectrolyte complexes in dilute solution can spontaneously form hollow spherical particles with thin continuous shells (vesicles) or with porous shells (perforated vesicles) if the polyions forming the complex differ in their affinity for the solvent. The solvent was considered good for the nonionic groups of one macroion and its quality was varied for the nonionic groups of the other macroion. It was found that if the electrostatic interactions are weak compared to the attraction induced by the hydrophobicity of the monomer units, the complex in poor solvent tends to form "dense core–loose shell" structures of different shapes. The strong electrostatic interactions favor the formation of the layered, the hollow, and the filled structured morphologies with the strongly segregated macroions. Vesicles with perforated walls were distinguished as the intermediate between the vesicular and the structured solid morphologies. The order parameter based on the spherical harmonics expansion was introduced to calculate the pore distribution in the perforated vesicles depending on the solvent quality. The conditions of the core–shell and hollow vesicular-like morphologies formation were determined theoretically via the calculations of their free energy. The results of the simulation and theoretical approaches are in good agreement. [ABSTRACT FROM AUTHOR]

The radiation-chemical synthesis of metal nanoparticles embedded into polymer matrices is an effective tool for preparation of the composite materials with very useful functional properties. This paper presents a review of an original approach to a single-step production of such materials via the radiation-induced reduction of the interpolyelectrolyte complex (IPEC) films containing metal ions under heterogeneous conditions, including the most recent results, and analysis of the prospects of this approach and its implications. First, the properties of IPECs as precursors for nanocomposites are briefly considered. Particular impact is given to the mechanistic aspects and principles of control of the nanoparticle formation and assembling at different stages. A common procedure of the radiation-chemical synthesis of metal polymer nanocomposites in the IPEC matrices implies irradiation of swollen films in an aqueous – organic environment. The kinetics of ion reduction and formation of nanoparticles was monitored by EPR and optical spectroscopy, whereas the obtained nanocomposites were characterized by TEM and diffraction methods. Using IPEC matrices allows us to reveal different stages of formation of metal nanostructures over a wide range of absorbed doses. Furthermore, it is possible to manipulate the processes of nucleation and growth of nanoparticles using both physical and chemical factors. Different kinds of radiation (e-beams, γ- and X-rays) were used in the experiments. It was shown that the penetration depth, dose rate and total absorbed dose had strong effect on the effect on nanoparticle size and their spatial distribution. The most striking feature were found for the processes induced by X-ray radiation. Detailed studies of this particular case revealed a very interesting effect described as radiation-chemical contrast, which is manifested by local intensification of the radiation-induced processes in the vicinity of existing nanoparticles. In addition to metal nanoparticles of different transition and noble metals, it was possible to obtain the bimetallic nanostructures within the IPEC matrix. Such nanocomposites may be potentially used as optical and magnetic materials, sensors, bactericide and fungicide products. The possibility of variation of nanoparticle size and specific properties of the IPEC films is crucially important for particular applications. [ABSTRACT FROM AUTHOR]

At present, a large amount of research from experimental and theoretical points of view has been done on interpolyelectrolyte complexes formed by electrostatic attractive forces and/or interpolymer complexes stabilized by hydrogen bonds. By contrast, relatively less attention has been given to polymer–polymer complex formation with synthetic polyampholytes (PA). In this review the complexation of polyampholytes with polyelectrolytes (PE) is considered from theoretical and application points of view. Formation of intra- and interpolyelectrolyte complexes of random, regular, block, dendritic polyampholytes are outlined. A separate subsection is devoted to amphoteric behavior of interpolyelectrolyte complexes. The realization of the so-called "isoelectric effect" for interpolyelectrolyte complexes of water-soluble polyampholytes, amphoteric hydrogels and cryogels with respect to surfactants, dye molecules, polyelectrolytes and proteins is demonstrated. [ABSTRACT FROM AUTHOR]