Polymer Complex Formation Research Articles

PH-sensitive semi-interpenetrating network of microcrystalline cellulose and methacrylic acid hydrogel for the oral delivery of insulin

Insulin is commonly administered to diabetic patients subcutaneously and has shown poor patient compliance. Due to this, research has been carried out extensively to find molecules that could deliver insulin orally. In this context, a new type of pH-responsive hydrogel, composed of microcrystalline cellulose and methacrylic acid-based hydrogels, has been developed and studied for the oral delivery of insulin. These hydrogels were prepared by free radical polymerization using potassium persulphate as initiator and N, N’-methylenebisacrylamide as a cross-linker. These pH-sensitive hydrogels showed swelling in distilled water as high as 5800 %. The hydrogels were investigated for swelling in saline and glucose solutions, and pH sensitivity was confirmed by swelling in solutions of different pH. The morphological shape was established by SEM, and the structure was analyzed by FTIR. Thermal degradation was investigated by TGA. In vitro release studies have confirmed pH sensitivity, showing lower insulin release at pH 1.2 than at pH 6.8. The encapsulation efficiency was determined to be 56.00 ± 0.04 %. It was further validated by in-vivo investigations for which insulin was loaded into hydrogels and administered orally to healthy and diabetic Wistar rats at 40 IU/kg, showing maximum hypoglycemic effect at 6 h, which was sustained for 24 h. In the stomach’s acidic environment, the gels remained unaffected due to the formation of intermolecular polymer complexes. Insulin remained in the gel and was protected from proteolytic degradation. Thus, pH-responsive methacrylic acid-based hydrogels are promising for biomedical applications, especially oral drug delivery.

Sorption of the Cu, Gd, V, Mn, and Fe elements by hydrogels with identification of their complexes in the solid phase of the polymer ligand using EPR

The search for new sorbents for the concentration of substances is among the important tasks of analytical chemistry regarding the monitoring of water bodies in modern times. It is necessary to regularly control water supply sources, and the quality of natural water is also an indicator of the health of ecosystems. The use of sorbents when collecting water for analysis simplifies the preparation of complex samples, allowing to use a solid concentrate to determine the absorbate and quickly record the results using multi-element in situ instrumental methods. We suggested using cross-linked polyacrylates (CLPs) based on polyacrylamide as a new type of sorbent for these purposes. Unlike traditional sorbents, hydrogels noticeably swell in water (рН 4-7), which allows conducting the sorption of elements not only on the surface but also inside CLP granules. Sorption is conducted in a static mode by placing a weighed portion of CLP in a certain volume of water sample and by further drying in air at 70-100°C. The purpose of this work was to obtain and study solid polymer concentrates of CLP using EPR spectroscopy in order to confirm the sorption of elements in CLP for the further development of methods for the preparation of samples of various water bodies. To do this, we obtained individual and binary polymer complexes of paramagnetic elements Cu(II), Gd(III), V(IV), Mn(II), and Fe(III) from model solutions of their salts (from 10-7 (INAA) to 10-3 (EPR) mol/dm3) and dried them To confirm the sorption and reliable binding of elements into polymer complexes, we used ESR spectroscopy at 293 K. The experimentally obtained new EPR spectra were compared with the theoretical ones. Complex EPR spectra were simulated using original software developed at the Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences. It was shown that upon drying CLPs completely disengaged from water molecules, while the sorption of metals depended on the рН and grew with an increase in the solution’s рН. In case of joint presence, metal ions formed more complex compounds as compared to individual sorption. The hyperfine structure constant (HSC) was calculated for the spectra of complexes with CLPs and g-factor was calculated for all samples. It was determined that in the course of the formation of metal complexes with CLPs, the nearest coordination sphere was greatly distorted, while the nature of the distortion of the ligand environment depended on the element. In case of the Cu(II) and V(IV) system, we observed additivity of the EPR spectra, but in case of Cu and Gd(III) it was not recorded. In any case, the formation of strong and stable polymer complexes was confirmed. Sorption concentration using CLPs was proposed as a method of sample preparation of natural and technogenic water systems by transferring the determined ions into a solid hydrogel concentrate in order to be further analysed using multi-element instrumental methods (for example, X-ray fluorescence analysis (XRF), instrumental neutron activation analysis (INAA), etc.).

Complex formation of 1D-coordination poly-mers based on arendiyl-bisphosphinic acid

Within the framework of the density functional theory and the ab initio pseudopotential, we have obtained the spatial distributions of the valence electrons density, the electron energy spectra and the atom charge states of 1D-coordination polymers based on arendiyl-bisphosphinic acids and metal ions. Formation of one-dimensional polymer chains takes place under participation of strong intermolecular bonds.

Donor–acceptor polymer complex formation in solution confirmed by spectroscopy and atomic-scale modelling

Donor polymer PBDB-T and acceptor polymer PF5-Y5 form D–A complexes in solution, as confirmed by combined absorption, excitation, and emission spectroscopy of blend solutions.

Tailoring a UCST-LCST-pH Multiresponsive Window through a Single Polymer Complex of Chitosan-Hyaluronic Acid.

Multistimuli-responsive polymers are important for controlled release. Owing to the fact that these polymers are derived from vinyl-based monomers, their decoration with other molecules is limited. Polysaccharides, especially chitosan (CS) and hyaluronic acid (HA), are pH-responsive biopolymers, whose chemical structures contain reactive functional groups for feasible chemical modifications to obtain add-on functions. The present work demonstrates the introduction of polymers with upper critical solution temperature (UCST) and lower critical solution temperature (LCST) performances onto CS and HA, respectively. By simply varying the mole ratio between the CS-containing UCST polymer and the HA-containing LCST polymer along with adjusting the pH, a polymer system with a UCST-LCST-pH multiresponsive window can be obtained. This multiresponsive window enables us to control the encapsulation and release with repeatability as evidenced from a model study on lysozyme. The present work, for the first time, shows a simple approach to obtain multiresponsive biodegradable polymers through the formation of a single polymer complex to tailor a specific multiresponsive window.

Structural and spectroscopic studies of Na+ – Quercetin-5′-sulfonic acid polymeric complexes obtained via solvothermal synthesis

New sodium complexes of quercetin-5′-sulfonic acid (HQSA) have been obtained. The aqua complex of the general formula [NaQSA∙(H2O)2]·2H2O (1) was a starting compound for solvothermal syntheses of acetone and dimethylsulfoxide (S) complexes: [NaQSA(S)](S) (2 – acetone) and [NaQSA(S)]∙2(S) (3a and 3b – DMSO). The fourth complex obtained from the reaction of HQSA excess used in the reaction with NaOH is [Na(QSA)2·2H2O][(EtOH)2H] (4). The molecular and crystal structures of 1 – 4 were determined by X-ray crystallography. The sodium cations are coordinated by six or seven oxygen atoms; Na+ coordinating groups are sulfonic, hydroxyl, and carbonyl of the QSA− anion. The bridging role of some functional groups causes the formation of polymeric complexes. The coordination spheres are completed by oxygen atoms from the coordinating water (in 1 and 4), acetone (2) or DMSO molecule (3a and 3b). In each structure non-coordinating interstitial solvate molecules are also present; they are two H2O (1), acetone (2), two DMSO (3a and 3b), and the hydrogen bisethanol cation [EtOH…H+…EtOH] (4). The last of these is a rare type of Zundel type cation. Unstable complexes (2 and 3), that decompose under normal conditions, are formed and they have a structure of intercalation clathrates. The solvating molecules, located between 1D or 2D polymeric complexes, play a unique role as a network bonding agent. Theoretical calculations showed charge separation between Na+ and SO3−. The FTIR and Raman spectra are consistent with the solved crystal structures and, importantly, enable the identification of acetone and DMSO molecules in the powder samples.

Сalixresorcine cavitands bearing lipophilic cationic fragments in the construction of mitochondrial-targeting supramolecular nanoparticles

The development of mitochondrial-targeting therapeutic nanoparticles is one of the crucial tasks of nanotechnology and nanomedicine. Here the study of supramolecular macrocycles decorated by lipophilic cationic mitochondrial-targeting fragments in the formation of supramolecular nanoparticles with the potential mitochondria-dependent apoptosis ability is described. Four cavitands based on tetrapentyl- and tetraundecylcalix[4]resorcines were functionalized with pyridinium (С5-Pyr and C11-Pyr, respectively) and triethylammonium groups (С5-NEt3 and C11-NEt3, respectively). Cavitands demonstrate amphiphilic character with critical association concentration values of 1.21, 1.20, 0.27 and 0.13 mM for С5-Pyr, С5-NEt3, C11-Pyr, and C11-NEt3, respectively (DMSO/Н2О 5/95 v/v, conductometry), and form small self-associates (D2O, DMSO-d6/D2О 5/95 v/v, FT-PGSE NMR method). The supramolecular modification of cavitands self-associates by the formation of polymer complexes with biocompatible polymer alginate sodium (AlgNa) was carried out. It was found that the size and stability of polymer complexes depends on the cavitand choice; the average hydrodynamic diameter of particles is 142 nm for С5-Pyr + AlgNa, 122 nm for С5-NEt3 + AlgNa and C11-NEt3 + AlgNa, and 615 nm for C11-Pyr + AlgNa complexes (DLS method). The formation of polymer complexes mainly is the result of electrostatic interaction and leads to the binding of cavitands by alginate in the form of self-associates (electrophoretic light scattering method, IR, fluorimetry). It was shown that pentylcavitands С5-Pyr and С5-NEt3 show higher hemotoxicity and cytotoxicity against normal (Chang liver cells) and tumor cells (M-HeLa cells) than undecylcavitands C11-Pyr and С11-NEt3. It was found that cavitand С5-NEt3 reduces the mitochondrial membrane potential and leads to the increase of ROS in M-HeLa cells (Flow cytometry analysis). However С5-NEt3 + AlgNa complex loses the ability to reduce the membrane potential of mitochondria, the possible reason of which is discussed.

A new method for the synthesis of polynuclear carboxylate complexes of technetium (II, III)

Acetates of actinides and their fission products were essential for the development of radiochemical industries using acetate precipitation technology. Despite this, the literature describes only the synthesis of species containing technetium in the oxidation state +3 and higher. New synthetic routes for the preparation of technetium +2.5 carboxylate polymer clusters using readily available technetium (IV) oxide as a precursor are developed in the present study. The crystal structure of synthesized complexes is studied by X-ray diffraction analysis (XRD) at different temperatures, and the coefficients of thermal expansion along the axes of the crystal lattice and in the direction of the polymer chain growth are determined. Matrix assisted laser desorption/ionization–time of flight (MALDI–ToF) mass-spectrometry showed stability of technetium carboxylates under conditions of laser ionization, which allows suggesting the possibility of technetium coatings deposition from the gas phase. Based on the obtained experimental results a reaction mechanism for the formation of tetracarboxylate oligomeric and polymer complexes of technetium was proposed. Stable oligomeric tetracarboxylate technetium clusters formed in acetic acid solutions can be used to create radiopharmaceuticals.

Preparation and characterization of poly-Schiff base cobaltcopper phthalocyanine bimetallic complex

Schiff bases can undergo coordination reactions with metals to form polymer complexes. The method of synthesizing Schiff base is simple and easy to operate. This article mainly synthesizes mononuclear metal copper phthalocyanine and polymer o-phthalimide salicylaldehyde Schiff base cobalt-copper phthalocyanine bimetallic complex, and the Schiff base complex. It is analyzed and characterized by infrared, ultraviolet and scanning electron microscopy.

Microfluidic fast chiral separation of baclofen and phenylalanine enantiomers based on cyclodextrin-electrokinetic chromatography

A green chiral lab-on-a-chip cyclodextrin-based microchip electrophoretic method was developed for enantioseparation of baclofen (BCN) and phenylalanine (Phe) enantiomers for the first time. All BCN and Phe enantiomers were offline labeled with 4-fluoro-7-nitrobenzofurazan (NBD-F) or fluorescein-5-isothiocyanate (FITC) fluorogenic reagents prior to microfluidic injection in a dynamically coated polymethylmethacrylate microchip. The enantioseparation was performed using borate buffer solution (50 mM; pH 9.5) containing a dynamic coating polymer (methylcellulose) and a chiral selector of cyclodextrin (CD) family as the background electrolyte. The combination of sieving properties of methylcellulose polymer and inclusion complex formation properties of the cyclodextrins rendered a novel green pseudo-stationary phase for the microfluidic chiral separation of the studied enantiomers in short separation time. Seven CD chiral selectors were investigated in our study to illustrate the proposed enantioseparation mechanism in the dynamically coated microfluidic channels. The results indicated that use of a modified cyclodextrin, heptakis-(2,6-di-O-methyl)-β-cyclodextrin (HDM-β-CD), resulted in extra interactions with the analytes of interest, leading to extra resolution with high number of theoretical plates. Therefore, HDM-β-CD was able to separate the NBD-labeled and FITC-labeled enantiomers of BCN and Phe within short analytical time. Sensitivity problem of microchip electrophoresis was overcome by application of field-enhanced injection stacking which improved sensitivity to a higher extent by online preconcentration of the labeled enantiomers in the microfluidic channels. The method was fully validated and successfully applied for the assay of BCN enantiomers and Phe enantiomers in their pure racemic mixtures. Moreover, the developed method was applied for precise analysis of BCN enantiomers in pharmaceutical formulations and in biological samples. The extraction recovery values of BCN enantiomers in biological samples were > 87.5% and %RSD < 7.0.

Complex Formation of Sulfobetaine Surfactant and Ionic Polymers and Their Stimuli Responsivity.

We investigated the kinds of complexes sulfobetaine surfactant and ionic polymer formed using lauramidopropyl hydroxysultane (LAPHS) as a sulfobetaine surfactant, poly(sodium styrenesulfonate) (PSSNa) as the anionic polymer and poly[3-(methacrylamido)propyl trimethylammonium chloride] (PMAPTAC) as the cationic polymer. The fundamental properties of LAPHS at various salt concentrations were estimated by various measurements, and it was confirmed that the LAPHS micelles alone did not show temperature responsiveness. The presence of large aggregates in addition to LAPHS micelles was confirmed in the aggregates prepared by adding PSSNa to LAPHS at a charge ratio of 1:0.5, 1:1, and 1:2. However, the aggregates could not be formed when the salt concentration was high or when a monomer was added instead of the polymer. This revealed that the cation part of sulfobetaine, which is the shell of LAPHS micelles, and the anion part of PSSNa electrostatically interacted with each other to form a large aggregate. On the other hand, unlike the case of LAPHS micelles alone and the aggregate consisting of LAPHS micelles and PSSNa, the aggregate of LAPHS micelles and PMAPTAC showed an unprecedented phenomenon of "clear → opaque → clear" with increasing concentration in the concentration range above CMC. The change in the transition temperature due to the change of concentration was a factor. Additionally, we confirmed that the transition temperature was lowered when the concentration was higher than CMC or the salt concentration was increased, and the transition temperature was increased when the PMAPTAC with a high degree of polymerization was added. These results suggested that the LAPHS micelles and the ionic polymer form an aggregate, and the temperature responsivity can be expressed by the interaction with the cationic polymer.

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro.

The aim of this study was to develop hydrophobic ionic drug polymer complexes in order to provide sustained drug release from self-emulsifying drug delivery systems (SEDDS). Captopril (CTL) was used as an anionic model drug to form ionic complexes with the cationic polymers Eudragit RS, RL, and E. Complexes of polymer to CTL charge ratio 1:1, 2:1, and 4:1 were incorporated in two SEDDS, namely FA which was 40% Kolliphor RH 40, 20% Kolliphor EL, and 40% castor oil and FB, which was 40% Kolliphor RH 40, 30% glycerol, 15% Kolliphor EL, and 15% castor oil. Blank and complex loaded SEDDS were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential. Resazurin assay was performed on Caco-2 cells to evaluate the biocompatibility of SEDDS. Release of CTL from SEDDS was determined in release medium containing 0.2 mg/mL of 5,5′-dithiobis(2-nitrobenzoic acid) (DNTB) allowing quantification of free drug released into solution via a thiol/disulfide exchange reaction between CTL and DNTB forming a yellow dye. The droplet size of SEDDS FA and SEDDS FB were in the range of 100 ± 20 nm and 40 ± 10 nm, respectively, with a PDI < 0.5. The zeta potential of SEDDS FA and SEDDS FB increased after the incorporation of complexes. Cell viability remained above 80% after incubation with SEDDS FA and SEDDS FB in a concentration of 1% and 3% for 4 h. Without any polymer, CTL was entirely released from both SEDDS within seconds. In contrast, the higher the cationic lipophilic polymer to CTL ratio in SEDDS, the more sustained was the release of CTL. Among the polymers which were evaluated, Eudragit RL provided the most sustained release. SEDDS FA containing Eudragit RL and CTL in a ratio of 1:1 released 64.78 ± 8.28% of CTL, whereas SEDDS FB containing the same complex showed a release of 91.85 ± 1.17% within 1 h. Due to the formation of lipophilic ionic polymer complexes a sustained drug release from oily droplets formed by SEDDS can be achieved. Taking into account that drugs are otherwise instantly released from SEDDS, results of this study might open the door for numerous additional applications of SEDDS for which a sustained drug release is essential.

Selection of best composition of Na+ ion conducting PEO-PEI blend solid polymer electrolyte based on structural, electrical, and dielectric spectroscopic analysis

In this paper, we report the investigation on structural, electrical, dielectric properties, and ion dynamics of novel blend polymer electrolyte matrix (PEO-PEI) complexed with sodium hexafluorophosphate salt. All the solid polymer electrolyte films have been synthesized via solution cast method. The SPE films were characterized by the X-ray diffraction, field emission scanning electron microscope, impedance-dielectric spectroscopy, and thermogravimetric analysis. The morphology of the SPE alters with salt addition and confirms the blend polymer complex formation. The FTIR analysis evidenced the complex formation, and increase in the fraction of free ions is achieved. The ionic conductivity exhibits a maximum at the stoichiometric ratio O/Na = 10 and follows the Arrhenius behavior. The fraction of free ions is maximum for the SPE film with the highest ionic conductivity. The optimum electrolyte possesses a voltage stability window of about 4 V, excellent thermal stability up to 380 °C, and high ionic transference number (~ 1). The complex permittivity and conductivity have been simulated in whole frequency window to extract relaxation time and dielectric strength. The dielectric constant and relaxation time exhibited sequentially a maximum and minimum for the SPE film with the highest ionic conductivity. The loss tangent peak shifts toward high frequency with addition of salt, and it infers the faster ion dynamics in the polymer matrix. Then the ion transport parameters number density of charge carriers (n), ion mobility (μ), and diffusion coefficient (D) have been obtained by three methods (FTIR, impedance spectroscopy, and loss tangent method) and are in absolute correlation with the impedance results. An ion transport mechanism has been proposed based on experimental findings.

Anionic copolymers of acrylamide and polyacrylic acid as hydroaccumulating polymeric materials

A method for hydrogels production by the formation of cross-linked binary polymer complexes is proposed. Necessary conditions for synthesis were determined, providing a high degree of swelling of hydroaccumulating polymeric materials based on anionic copolymers of acrylamide and polyacrylic acid. Chemical interaction of components of polymer complex has been proved by the methods of infrared spectroscopy and potentiometric titration. The possibility of moisture absorption control of hydrogels depending on synthesis conditions and application purpose was shown.

Amino Acid-Substituted Dextran-Based Non-Viral Vectors for Gene Delivery.

To form bio-inspired non-viral vectors for DNA delivery, the polysaccharide dextran is allowed to react with Boc-amino protected amino acids glycine, β-alanine, and L-lysine activated with 1,1'-carbonyldiimidazole and subsequent dextran ester deprotection. A library of such dextran esters is made available to investigate the relationship between polymer structure, complex formation, stability, toxicity, and transfection. Only dextran esters of β-alanine and L-lysine are able to efficiently interact with DNA as shown by dye exclusion assays, to form nanosized complexes (70-110 nm) with positive zeta potential. With increasing substitution degree and complex charge ratios, the L-lysine esters accomplish more effective binding and protection of DNA against enzymatic degradation than β-alanine esters. However, luciferase reporter gene assays reveal higher transfection for β-alanine than for L-lysine esters due to a more effective DNA release and better suited buffing area of the amino groups triggering the endosomal release. Conclusively, β-alanine-substituted dextran derivatives may serve as promising non-viral vectors.

Preparation and Thermoelectric Properties Study of Bipyridine-Containing Polyfluorene Derivative/SWCNT Composites.

Polymer/inorganic thermoelectric composites have witnessed rapid progress in recent years, but most of the studies have focused on the traditional conducting polymers. The limited structures of traditional conducting polymers restrain the development of organic thermoelectric composites. Herein, we report the preparation and thermoelectric properties of a series of composites films based on SWCNTs and bipyridine-containing polyfluorene derivatives. The value of the power factor around 12 μW m−1 K−2 was achieved for the composite F8bpy/SWCNTs with a mass ratio of 50/50, and the maximum value of 62.3 μW m−1 K−2 was obtained when the mass ratio reached 10/90. Moreover, taking advantage of the bipyridine unit could chelate various kinds of metal ions to form polymer complexes. The enhanced power factor of 87.3 μW m−1 K−2 was obtained for composite F8bpy-Ni/SWCNTs with a mass ratio of 50/50. Finally, the thermoelectric properties of the bipyridine-containing polyfluorene derivative/SWCNT composites were conveniently tuned by chelating with different metal ions.

Intra- and Interpolyelectrolyte Complexes of Polyampholytes.

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.

Conductivity and structural studies of PVA based mixed-ion composite polymer electrolytes

The solid membranes having different ratios of poly-vinyl alcohol (PVA), sodium perchlorate (NaClO4) and lithium perchlorate (LiClO4) were prepared using solution casting technique. The mixed-ion composite polymer electrolytes were characterized by X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR) and conductivity measurement investigations. The XRD study confirms the amorphous nature of the mixed-ion composite polymer electrolytes. FTIR analysis has been used to characterize the structure of polymer which confirms the polymer and salt complex formation. The temperature dependent nature of ionic conductivity of the mixed-ion composite polymer electrolytes was determined by using conductivity meter (EC-035WP ERMA Inc, made in Japan). The ionic conductivity of the electrolyte was found in the range of 10-3 - 10-4 S/cm at room temperature.

New Metal Complexes Derived from Guanidine-Containing Dialdehyde Cellulose

New metal-polymer complexes of iron-containing composites of dialdehyde cellulose with guanidine acrylate or methacrylate have been developed. The structure and properties of these materials have been established by physicochemical testing. The polymeric iron-containing complexes obtained by radical polymerization (in situ) are formed due to intra- and intermolecular coordination of the metal ions with carboxylate oxygen atoms, and amino group nitrogen atoms of the guanidine fragment as well as hydroxyl groups of dialdehyde cellulose. The complexes obtained by mixing the metal salt with polymers in aqueous solution are formed due to replacement of water molecules in the coordination sphere of the solvated metal ions by hydroxyl groups of dialdehyde cellulose and the reaction of metals with carboxylate ions and guanidine groups of the polymer located on the composite surface. Guanidine-containing cellulose composites were found to be effective matrices for stabilizing the size of the growing particles containing a new metallic phase and to form polymer complexes with a narrow size distribution of both micro- and nanoparticles. These results suggest that the synthesized compounds hold promise for reagent transport when using composites as catalysts for various chemical reactions or for targeted delivery of drugs.

Synthesis and Complex Formation of Porphyrin Polymers on the Basis of Methyl Methacrylate

Copolymers of methyl methacrylate with various porphyrin monomers were prepared by radical copolymerization in solution. The yields, molecular weight characteristics of the copolymers and the molar content of porphyrin in the copolymers were determined. Copper and zinc complexes of the synthesized porphyrin polymers were obtained.