Stability Of Polyelectrolyte Complexes Research Articles

Polyelectrolyte complexes of chitosan and hyaluronic acid or carboxymethylpullulan and their aminoguaiacol derivatives with biological activities as potential drug delivery systems

Polyelectrolyte complexes (PECs) were elaborated from chitosan as cationic polymer and carboxy-methylpullulan (CMP), hyaluronic acid (HA) and their derivatives grafted with aminoguaiacol (G) with different degrees of substitution (DSGA) with the aim of obtaining nanogels for drug delivery. For each couple of polysaccharides, the charge ratios giving the smaller size with the lower PDI were selected to produce PECs. CMP_CHIT and CMP-G_CHIT PECs had smaller sizes (220–280 nm) than HA_CHIT and HA-G_CHIT PECs (280–390 nm). PECs were stable at 4 °C during 28 days at pH 5. In phosphate buffer saline (PBS) at pH 7.4, at 4 °C, a better stability of PECs based on CMP-G derivatives was observed. The hydrophobic associations between aminoguaiacol groups (highlighted by measurements of pyrene fluorescence) led to a better PECs' stabilization in PBS. The PECs' antioxidant and antibacterial activities were demonstrated and related to the DSGA. Diclofenac and curcumin were used as drug models: their loading reached 260 and 53 μg/mg PEC, respectively. The release of diclofenac in PBS at 37 °C followed a quasi-Fickian diffusion mechanism with release constant between 0.88 and 1.04 h−1. The curcumin release followed a slow linear increase in PBS/EtOH (60/40 V/V) with an effect of DSGA.

New insights into physicochemical aspects involved in the formation of chitosan@alginate biobased polyelectrolyte complexes on natural montmorillonite clay surface

The use of alginate@chitosan-based polyelectrolyte complexes (PEC) in encapsulation process is common due to the electrostatic interactions between the two oppositely charged biopolymers. However, the incorporation of montmorillonite (Mt) particles in the complex formation for improving the encapsulation efficiency as well as the physicochemical properties of PEC remains a challenge due to the competitive polymer–polymer and polymer-nanoparticle interactions. This study aimed to investigate the binding mechanism of alginate and chitosan through layer-by-layer approach in the presence of montmorillonite nanoparticles as a function of pH and the addition order of the components. Various techniques were employed to examine the formation of the alginate@chitosan PEC on the surface of Mt, such as zeta potential, conductivity and turbidity measurements. The characterization of the different PEC systems was performed using Fourier Transformed Infrared spectroscopy (FTIR), X-Ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and thermogravimetry analysis (TGA). The results indicate that the formation of the complex is pH-dependent. The highest intercalation of the complex was observed when chitosan was added first at a lower pH, while the intercalation was reduced at neutral pH. Additionally, the thermal stability of PEC was enhanced in the presence of montmorillonite, and was dependent on both pH and the order of addition of the biopolymers. This study provides a new understanding of the complex formation mechanism between alginate and chitosan in the presence of montmorillonite nanoparticles, showing that the combination of biopolymer-based PEC with clay particles can potentially provide a low-cost, more stable and effective nanocomposite for encapsulation and delivery of active agents.

A Novel Family of Stable Polyelectrolyte Complexes Based on Mixed Olefins-Maleic Anhydride Copolymer.

In the present study, the copolymer of mixed olefins included in unetherified gasoline and maleic anhydride (PUGM) was prepared by self-stabilized precipitation polymerization (2SP) and employed for the synthesis of a new family of stable polyelectrolyte complexes (PECs). Polyanionic saponified PUGM partially grafted with methoxy poly(ethylene glycol) (PUGMS-g-mPEG) and polycationic quaternized PUGM (PUGMQ) were both derived from PUGM via the facile modification of anhydride groups. The particle size, zeta potential, morphology, and stability of self-assembled PEC particles were investigated thoroughly. Strikingly, the introduction of long mPEG side chains (Mn = 4000) had a remarkable effect on the self-assembled particles, which displayed a constant particle size of ∼200 nm regardless of varying n+/n-. Moreover, it also enhanced the salt tolerance and long-term stability of PEC particles significantly. Our work not only provides an effective approach to PECs from petroleum resources with low cost but also deepens the understanding of the relationship between the chain structure of polyelectrolytes and the stability of PECs.

Versatile and High-Throughput Polyelectrolyte Complex Membranes via Phase Inversion.

High-flux filtration membranes constructed through scalable and sustainable methods are desirable for energy-efficient separations. Often, these criteria are difficult to be reconciled with one another. Polymeric membranes can provide high flux but frequently involve organic solvents in processing steps. Solubility of many polymeric membranes in organic media also restricts their implementation in solvent filtration. In the present work, we report a simple and high-throughput aqueous processing approach for polyelectrolyte complex (PEC) membranes with controllable porosity and stability in various aqueous and organic environments. PECs are materials composed of oppositely charged polymer chains that can form solids in aqueous environments, yet which can be dissolved in very specific salt solutions capable of breaking the interpolymer ion pairs. By exploiting the salt-induced dissolution and subsequent reformation of the complex, nano- to microporous films are rapidly synthesized which resemble membranes obtained through conventional solvent-phase inversion techniques. PECs remain stable in organic solvents because of the low dielectric constant of the environment, which enhances electrostatic interactions, making them suitable for a wide range of water and solvent filtration applications. Here, we elucidate how the polymer-phase behavior can be manipulated to exercise morphological control, test membrane performance for water and solvent filtration, and quantify the mechanical stability of PECs in relevant conditions.

Thermodynamic mechanism of particulation of sodium alginate and chitosan polyelectrolyte complexes as a function of charge ratio and order of addition

This study focused on mechanistic understanding of the effect of charge ratio, order of addition and resulting thermodynamics of interaction on the formation and properties of polyelectrolyte complexes (PECs) from sodium alginate and chitosan at a constant tightly controlled pH 4 where the zeta potential difference was maximum for the formation of PECs. The morphology, particle size and particle size distribution as well as the stability of PECs were investigated as a function of molar charge ratio, and the order of addition. The association binding constant Ka and the stoichiometry of interaction between the two electrolytes, evaluated using Isothermal titration calorimetry, showed that the stoichiometry and enthalpy of reactions were strongly affected by the order of addition and influenced the average particle size and zeta potential of PECs. The addition of alginate (-) into chitosan (+) gave positively charged particles and resulted in stronger interactions characterized by larger enthalpy and entropy of complexation which led to smaller particles. Reversing the order of addition gave negatively charged particles that were larger. Morphologies of complexes studied using scanning electron microscopy (SEM) showed distorted spherical particles for both orders of addition and at most charge ratios. Stability during 8 weeks was found to depend on the order of addition and charge ratio. Alginate in chitosan gave more stable PECs consistent with the thermodynamics of interaction which showed stronger interactions for this order of addition. The particle sizes and size distributions rapidly increased near electrical neutrality during storage at 4 °C where aggregation was facilitated because of electrical neutrality but particles were stable when the net charge was either strongly positive or strongly negative.

Engineering Peptide-Based Polyelectrolyte Complexes with Increased Hydrophobicity.

Polyelectrolyte complexation is a versatile platform for the design of self-assembled materials. Here we use rational design to create ionic hydrophobically-patterned peptides that allow us to precisely explore the role of hydrophobicity on electrostatic self-assembly. Polycations and polyanions were designed and synthesized with an alternating sequence of d- and l-chiral patterns of lysine or glutamic acid with either glycine, alanine or leucine due to their increasing hydrophobicity index, respectively. Two motifs were considered for the oppositely charged patterned peptides; one with equal residues of charged and uncharged amino acids and the other with increased charge density. Mass spectroscopy, circular dichroism, H- and F-NMR spectroscopy were used to characterize the polypeptides. Polyelectrolyte complexes (PECs) formed using the sequences were characterized using turbidity measurements, optical microscopy and infrared spectroscopy. Our results show that the critical salt concentration, a key measure of PEC stability, increased with both increasing charge density as well as hydrophobicity. Furthermore, by increasing the hydrophobicity, the amount of PEC formed increased with temperature, contrary to purely ionic PECs. Lastly, we assessed the encapsulation behavior of these materials using a hydrophobic dye. Concluding that encapsulation efficiency increased with hydrophobic content of the complexes providing insight for future work on the application of these materials for drug delivery.

Chitosan-Based Polyelectrolyte Complexes for Doxorubicin and Zoledronic Acid Combined Therapy to Overcome Multidrug Resistance.

This study aimed to develop nanovectors co-encapsulating doxorubicin (Doxo) and zoledronic acid (Zol) for a combined therapy against Doxo-resistant tumors. Chitosan (CHI)-based polyelectrolyte complexes (PECs) prepared by ionotropic gelation technique were proposed. The influence of some experimental parameters was evaluated in order to optimize the PECs in terms of size and polydispersity index (PI). PEC stability was studied by monitoring size and zeta potential over time. In vitro studies were carried out on wild-type and Doxo-resistant cell lines, to assess both the synergism between Doxo and Zol, as well as the restoring of Doxo sensitivity. Polymer concentration, incubation time, and use of a surfactant were found to be crucial to achieving small size and monodisperse PECs. Doxo and Zol, only when encapsulated in PECs, showed a synergistic antiproliferative effect in all the tested cell lines. Importantly, the incubation of Doxo-resistant cell lines with Doxo/Zol co-encapsulating PECs resulted in the restoration of Doxo sensitivity.

Directing the phase behavior of polyelectrolyte complexes using chiral patterned peptides

Polyelectrolyte complexes (PECs) have a broad range of promising applications as soft materials due to their self-assembly and diversity of structure and chemical composition. Peptide polymer PECs are highly biocompatible and biodegradable, making them particularly useful for encapsulation of food additives and flavors, micellar drug delivery, medical and underwater adhesives, fetal membrane patches, and scaffolds for cell growth in tissue engineering. While parameters affecting PEC formation and stability in regards to charge effects are well researched, little is known about the effects of van der Waals interactions, hydrogen bonding, and secondary structure in these materials. Peptide chirality provides a unique opportunity to manipulate PEC phase to modulate the amount of solid-like (precipitate) or liquid-like (coacervate) character by influencing hydrogen bonding interactions among peptide chains. In previous work, we showed that chiral peptides form solid complexes, while complexes with even one racemic peptide were fluid. This raised the interesting question of how long a homochiral sequence must be to result in solid phase formation. In this work, we designed chiral patterned peptides of polyglutamic acid and polylysine ranging from 50 to 90% L-chiral residues with increasing numbers of sequential L-chiral residues before a chirality change. These polymers were mixed together to form PECs. We observed that 8 or more sequential L-chiral residues are necessary to achieve both the appearance of a precipitate phase and sustained β-sheets in the complex, as determined by optical imaging and FTIR Spectroscopy. Less homochiral content results in formation of a coacervate phase. Thus, we show that chiral sequence can be used to control the phase transition of PECs. Understanding how to manipulate PEC phase using chiral sequence as presented here may enable tuning of the material properties to achieve the desired mechanical strength for coatings and polymer brushes, or the most effective molecular release kinetics for drug delivery applications, for example.

Assembly and Reassembly of Polyelectrolyte Complex Formed by Poly(ethylene glycol)-block-poly(glutamate sodium) and S5R4 Peptide

The structure and stability of polyelectrolyte complex are controlled not only by electrostatic interaction but also by hydrogen bonding and hydrophobic interaction if they are present. The complexes formed by such multiple interactions should exhibit different responses to the environmental changes, such as ionic strength and pH. In this work, we designed a positively charged peptide S5R4, which can interact with poly(ethylene glycol)-block-poly(glutamate sodium) (PEG114-PGlu64) via electrostatic interaction, hydrogen bonding, and hydrophobic interaction. In deionized water at pH 7.1, the complexes formed by PEG114-PGlu64 and S5R4 assemble into wormlike micelles, spheres, and even hierarchical “wool balls”, depending on mixing ratio. However, a distinct dissociation–reassembly process is observed when 30 mM NaCl is added to screen the electrostatic interaction. The spheres transform into loose clusters after reassembly. This process is caused by the switch of driving force from electrostatic interaction ...

Synthesis and Characterization of Chitosan-Based Polyelectrolyte Complexes Doped with Xanthene Dyes.

Biocompatible chitosan-based polyelectrolyte complexes (PECs) doped with xanthene dyes (fluorescein, eosin Y, erythrosin B, rhodamine 6G) were synthesized and characterized by scanning electron microscopy, dynamic light scattering, zeta potential measurements, and absorption and luminescence (including polarized, time-resolved, and phosphorescence) spectroscopy. The results are discussed in terms of the mechanism and rigidity of dye-PEC binding, the heavy-atom effect in dyes and PEC stability. Eosin Y is found to be the optimal dopant, providing both a high dye content in PECs and a high quantum yield of fluorescence.

Effects of monovalent and multivalent ions on the stability of a polyelectrolyte complex with entrapped surfactants

In this article, we report the effects of nine different monovalent and multivalent salts on the particle size and stability of refined, positively charged polyelectrolyte complexes (PECs) with entrapped surfactant. Dynamic light scattering and ζ potential measurements of these polymeric particles as a function of various salt concentrations showed that both counter ions and co-ions induced a concentration-dependent increase in the particle size and a decrease in the ζ potential. We found that the anion concentration where the particle size doubled and the maximum anion concentration beyond which particle precipitation occurred (Ca,max) demonstrated a power law dependence on the anion valence. Moreover, for anions of the same valence but different hydration radio, Ca,max decreased in the following order: NO3 → Cl → HPO42− > SO42− > PO43−. However, unlike the case of hard colloids where co-ions have relatively little effect on particle interactions, the co-ions also increased the hydrodynamic radii of our PECs in the following order: K+ ≈ Na+ > Ca2+ > Mg2+ > Al3+. Furthermore, we found that the entrapped surfactants were shielded from the adverse effect of multivalent ions; this established that the monovalent and multivalent ions interacted with the polyelectrolyte shells of the PEC. This behavior was in contrast with the effect of salts on mixtures containing the polyelectrolyte and surfactant components, where the addition of salts typically causes an interaction with the individual components. Because several biomedical and technological applications involving PECs require saline environments, our studies provide insight into how small ions influence the PEC stability in applications involving varying salinities. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42099.

Characterization of polyelectrolytes complexes based on N,N,N-trimethyl chitosan/heparin prepared at different pH conditions

N,N,N-trimethyl chitosan (TMC) was synthesized through the N-methylation of chitosan (CHT) and characterized by FTIR and 1H NMR spectroscopy. Polyelectrolyte complexes (PECs) based on TMC and heparin (HP) were prepared at different pHs (5, 8, 10 and 12) and characterized through FTIR spectroscopy, DSC and TGA curves and WAXS profiles. It was verified that the higher the pH of feed solution used for the PEC formation the higher is the thermal stability of PECs. Under basic conditions, the complexation between TMC and HP was more effective and alterations on WAXS profiles of PECs in relation to the precursor (TMC) were clearly observed. In addition, WAXS profiles show that the PEC crystallinity depends on the pH used for the complexation. These results are consistent with the FTIR, DSC, and TGA data. Due to the more intense electrostatic interactions, at higher pHs the unlike polymers chains (TMC and HP) are close enough to produce more stable PECs.

Design of a stable and methanol resistant membrane with cross-linked multilayered polyelectrolyte complexes for direct methanol fuel cells

Sulfonated poly (arylene ether ketone) bearing carboxyl groups (SPAEK-C) membranes have been prepared as proton exchange membranes for applications in direct methanol fuel cells (DMFCs). Multilayered polyelectrolyte complexes (PECs) which applied as methanol barrier agents are prepared by alternate deposition of the oppositely charged amino-containing poly (ether ether ketone) (Am-PEEK) and the highly sulfonated SPAEK-C via a layer-by-layer method. The cross-linked PEC (c-PEC) is derived from a simple heat-induced cross-linking reaction between Am-PEEK and SPAEK-C. Fourier transform infrared spectroscopy confirms that Am-PEEK and SPAEK-C are assembled successfully in the multilayers. The morphology of the membranes is studied by scanning electron microscopy, which shows the presence of the thin layers coated on the SPAEK-C membrane. After PEC and c-PEC modification, the methanol permeability decreases obviously when compared to that of the pristine membrane. Notably, improved proton conductivities are obtained for the PEC modified membranes in comparison with the pristine membrane. Moreover, the selectivity of these modified membranes is one order of magnitude higher than that of Nafion 117. The thermal stability, oxidative stability, water uptake and swelling of PEC and c-PEC modified membranes are also investigated.

Adsorption and inhibition properties of associates based on water-soluble polymers

It was established on the basis of a set of physico-chemical data that polyelectrolyte complexes (PECs) are formed in a solution containing cation-active oligomers and low-molecular compounds. Here- with, the composition, structure, and stability of PECs depend on the ratio and nature of the initial ingredients. It was shown that the PECs formed in situ feature considerably higher adsorptivity on different interfaces as compared to the initial oligomers. This is due to an increase in the hydrophobicity of macroparticles under association and their enhanced displacement to the interface by the solvent and also an increase in the interaction of the PEC functional groups with the electrode surface due to conformation changes in the surface layer. An inhibiting effect of PECs in the case of Zn(II) ion discharge in polycrystalline electrode and that of Cd(II) on amalgam electrodes is considerably higher than in the case of the initial polyelectrolytes at similar concentrations, which is mainly due to the steric inhibition effect.

Complexation and competitive interpolyelectrolyte reactions involving a poly(N-oxyethyl-4-vinylpyridinium) cation

The interaction of a poly(N-oxyethyl-4-vinylpyridinium) cation with a polymethacrylate anion and DNA in aqueous and water-salt solutions has been studied by fluorescence quenching techniques with the use of pyrenyl-labeled polycarboxylic acid and the intercalating dye ethidium bromide. The presence of an OH group in each positively charged repeating unit of the polycation affects the stability of polyelectrolyte complexes against sodium chloride in a different manner. In the case of DNA, the destabilization of complexes is insignificant in the studied pH range (5.5–9.0). As regards the polymethacrylate anion, the complexes are stabilized and the transition from neutral to weakly acidic solutions causes an appreciable stabilization of the complex owing to formation of a system of hydrogen bonds between OH groups of a polycation and COOH groups of polycarboxylic acid. Despite a much higher stability of complexes based on a weakly ionized poly(methacrylic acid) against salt, in weakly acidic solutions, polycations predominantly bind to highly charged DNA, thus indicating the prevailing role of electrostatic interactions in complexation. The results of this study can be especially useful for designing pH responsive polyelectrolyte systems based on charged biopolymers (including polysaccharides) with controlled stability in water-salt solutions.

Interaction of water-soluble polypyridylphenylene dendrimers with a polymethacrylate anion

Cationic water-soluble dendrimers have been prepared by the alkylation of pyridyl groups in polypyridylphenylene dendrimers of the first four generations, and their interaction with a polymethacrylate anion has been studied. The stability of polyelectrolyte complexes in aqueoussaline solutions has been studied by fluorimetric titration with the use of the pyrenyl-tagged polyanion, and it has been shown that the stability of these complexes significantly increases with the dendrimer generation number and the content of hydrophobic phenylene groups. Based on sedimentation analysis and turbidimetric titration, it is inferred that a significant part of charged groups of dendrimers are inaccessible to interaction with the polyanion and that water-soluble nonstoichiometric polyelectrolyte complexes develop in mixtures of higher generation dendrimers. Modeling results of this study may be useful for designing efficient cationic dendrimer carriers of genetic material and hydrophobic physiologically active compounds.

Synthesis and characterization of soluble chitosan/sodium carboxymethyl cellulose polyelectrolyte complexes and the pervaporation dehydration of their homogeneous membranes

Soluble polyelectrolyte complexes (PECs) between chitosan (CS) and sodium carboxymethyl cellulose (CMCNa) were synthesized in aqueous hydrochloric acid (HCl) and obtained in their solid form. FT-IR, elemental analysis (EA), thermal gravity analysis (TGA), wide-angle X-ray diffraction (WAXD), and viscometry were used to characterize the chemical structure, composition, thermal stability, crystallinity and solution property of PECs, respectively. These PECs could be dissolved in aqueous NaOH and their homogeneous polyelectrolyte complex membranes (HPECMs) were made by solution casting method. Both the surface morphology of HPECMs and the morphology of single PEC aggregate were examined by field emission scanning electron microscope (FESEM), and atomic force microscopy (AFM). Effects of the water content in aqueous ethanol and temperature on the swelling behavior and pervaporation dehydration of HPECM were examined. A good performance of J = 1.14 kg/m 2 h, α = 1062 was obtained with HPECM0.25 in dehydrating 10 wt.% water–ethanol at 70 °C. The swelling behavior and pervaporation performance were interpreted in terms of structure characteristics of both PECs and HPECMs.

Pervaporation dehydration of isopropanol using homogeneous polyelectrolyte complex membranes of poly(diallyldimethylammonium chloride)/sodium carboxymethyl cellulose

Polyelectrolyte complexes (PECs) between poly(diallyldimethylammonium chloride) (PDDA) and sodium carboxymethyl cellulose (CMCNa) with four ionic complexation degrees (ICD) were synthesized and their homogeneous polyelectrolyte complex membranes (HPECMs) were fabricated. Elemental analysis and FT-IR were used to determine the composition and chemical structure of PECs. Thermogravimetric analysis (TGA), wide-angle X-ray diffraction (WAXD) and viscometry were used to characterize the thermal stability, crystallinity and solution properties of PECs, respectively. Field emission scanning electron microscope (FESEM) was used to examine the surface morphology of HPECMs, which were subjected to the pervaporation dehydration of isopropanol. Effects of membrane fabrication methods, cycling of feed temperature and ICD of PECs on pervaporation performance of HPECMs are discussed. Meanwhile, HPECMs were also subjected to dehydration of three other organics and showed very good performance. All these performances are explained in terms of the unique structural characteristics of PECs and HPECMs.

Peroral delivery of insulin using chitosan derivatives: A comparative study of polyelectrolyte nanocomplexes and nanoparticles

Polymeric delivery systems based on nanoparticles (NP) have emerged as a promising approach for peroral insulin delivery. Using a trimethyl chitosan (TMC) and a PEG- graft-TMC copolymer, polyelectrolyte complexes (PEC) and nanoparticles were prepared and their properties were compared. The amount of insulin was quantified by HPLC and the stability of PEC and NP upon exposure to simulated gastrointestinal (GI) fluid was monitored by dynamic laser light scattering. It was shown that polymer/insulin (+/−) charge ratio played an important role in PEC and NP formation. Stable, uniform, and spherical PEC/NP with high insulin association efficiency (AE) were formed at or close to optimized polymer/insulin (+/−) charge ratio, depending on polymer structure. All PEC were more stable in pH 6.8 simulated intestinal fluid (SIF) than NP. The PEC also appeared to play some role in protecting insulin from degradation at higher temperature and with proteolytic enzyme more efficiently than NP. On the basis of these results, polyelectrolyte complexation can be suggested as a potentially useful technique for generating insulin delivery systems for peroral administration.

Effect of Polycation Length on Its Complexation with DNA and with Poly(oxyethylene-block-sodium methacrylate)

Polyelectrolyte complexes of a synthetic polycation with either a genomic DNA or a synthetic poly(oxyethylene-block-sodium methacrylate), POE-b-PMANa, have been studied in aqueous solutions as a function of cation:anion ratio, the degree of polymerization of the polycation, the ionic strength, and temperature using dynamic light scattering and turbidity measurements. The polycation was a copolymer of methacryl oxyethyl trimethylammonium chloride and poly(oxyethylene) monomethyl ether monomethacrylate with 4-5 oxyethylene repeating units, PMOTAC-g-POE. The molar masses of the polycations in a homological series were 0.3, 0.9, and 2.1 x 10(6) g/ mol. The amount of comonomers with poly(oxyethylene) tails in the copolymers was 15 mol %. The molar mass of the POE-b-PMANa was 75000 g/mol and that of the POE-block was 5000 g/mol. The molar mass of the polycation was shown to have a dramatic effect on the stability and size of the complexes formed by either of the polyanions. An increase in the polycation molar mass shifts the cloud point toward the lower polycation content in the complexes, and a macro phase separation occurs in the solutions with the cation to anion molar ratios much below than 1:1. Increasing the ionic strength has a similar effect. Further addition of salt to turbid and phase-separated solutions results in dissociation of the complexes, and the polyions dissolve as individual macromolecules. The effect of POE on the stability of polyelectrolyte complexes is discussed as well.