Interactions between Hyaluronic Acid and Chitosan by Isothermal Titration Calorimetry: The Effect of Ionic Strength, pH, and Polymer Molecular Weight.

Hyaluronic acid (HA)/chitosan (CHI) complex coacervates have recently gained interest due to the pH-dependent ionization and semiflexibility of the polymers as well as their applicability in tissue engineering. Here, we apply isothermal titration calorimetry (ITC) to understand the apparent thermodynamics of coacervation for HA/CHI as a function of the pH, ionic strength, and chain length. We couple these ITC experiments with the knowledge of the charge states of HA and CHI from potentiometric titration to understand the mechanistic aspects of complex formation.

Polymeric pH-Responsive Metal-Supramolecular Nanoparticles for Synergistic Chemo-Photothermal Therapy.

Stimuli-responsive drug delivery carriers, particularly those exhibiting pH sensitivity, have attracted significant scholarly interest due to their promising potential in anticancer therapeutic applications. This phenomenon can primarily be ascribed to the inherently acidic nature of tumor microenvironments. However, pH-responsive carriers frequently require the incorporation of functional groups or materials sensitive to pH changes.

Deposition and water repelling of temperature-responsive nanopesticides on leaves.

Pesticides are widely used to increase agricultural productivity, however, weak adhesion and deposition lead to low efficient utilization. Herein, we prepare a nanopesticide formulation (tebuconazole nanopesticides) which is leaf-adhesive, and water-dispersed via a rapid nanoparticle precipitation method, flash nanoprecipitation, using temperature-responsive copolymers poly-(2-(dimethylamino)ethylmethylacrylate)-b-poly(ε-caprolactone) as the carrier. Compared with commercial suspensions, the encapsulation by the polymer improves the deposition of TEB, and the contact angle on foliage is lowered by 40.

Rheology and Gelation of Hyaluronic Acid/Chitosan Coacervates.

Hyaluronic acid (HA) and chitosan (CHI) are biopolyelectrolytes which are interesting for both the medical and polymer physics communities due to their biocompatibility and semi-flexibility, respectively. In this work, we demonstrate by rheology experiments that the linear viscoelasticity of HA/CHI coacervates depends strongly on the molecular weight of the polymers. Moduli for coacervates were found significantly higher than those of individual HA and CHI physical gels.

Chondro-inductive hyaluronic acid/chitosan coacervate-based scaffolds for cartilage tissue engineering.

Injuries related to articular cartilage are among the most challenging musculoskeletal problems because of poor repair capacity of this tissue. The lack of efficient treatments for chondral defects has stimulated research on cartilage tissue engineering applications combining porous biocompatible scaffolds with stem cells in the presence of external stimuli. This work presents the role of rat bone marrow mesenchymal stem cell (BMSC) encapsulated-novel three-dimensional (3D) coacervate scaffolds prepared through complex coacervation between different chitosan salts (CHI) and sodium hyaluronate (HA).

Effect of Protein Surface Charge Distribution on Protein-Polyelectrolyte Complexation.

Charge anisotropy or the presence of charge patches at protein surfaces has long been thought to shift the coacervation curves of proteins and has been used to explain the ability of some proteins to coacervate on the "wrong side" of their isoelectric point. This work makes use of a panel of engineered superfolder green fluorescent protein mutants with varying surface charge distributions but equivalent net charge and a suite of strong and weak polyelectrolytes to explore this concept. A patchiness parameter, which assessed the charge correlation between points on the surface of the protein, was used to quantify the patchiness of the designed mutants.

Hyaluronic Acid/Chitosan Coacervate-Based Scaffolds.

Chitosan-chloride (CHI) and sodium hyaluronate (HA), two semiflexible biopolymers, self-assemble to form nonstoichiometric coacervates. The effect of counterions was briefly investigated by preparing HA/CHI coacervates in either CaCl or NaCl solutions to find only a small difference in their tendency to coacervate. Higher water content in coacervates within CaCl was attributed to the chaotropic nature of Ca ions.

Thermodynamics of complex coacervation.

Isothermal titration calorimetry has routinely been used to understand the thermodynamic characteristics of complexation and coacervation. Most commonly, built-in models that assume independent binding sites have been employed in these studies. However, the non-covalent nature of interactions and steric effects accompanying macromolecules require (i) usage of new models such as overlapping binding sites and Satake-Yang's two-state binding models and (ii) reformed interpretations of the data as two-stage structuring.

Construction of Compact Polyelectrolyte Multilayers Inspired by Marine Mussel: Effects of Salt Concentration and pH As Observed by QCM-D and AFM.

Biomimetic multilayers based on layer-by-layer (LbL) assembly were prepared as functional films with compact structure by incorporating the mussel-inspired catechol cross-linking. Dopamine-modified poly(acrylic acid) (PAADopa) was synthesized as a polyanion to offer electrostatic interaction with the prelayer polyethylenimine (PEI) and consecutively cross-linked by zinc to generate compact multilayers with tunable physicochemical properties. In situ layer-by-layer growth and cross-linking were monitored by a quartz crystal microbalance with dissipation (QCM-D) to reveal the kinetics of the process and the influence of Dopa chemistry.

Complex coacervation of hyaluronic acid and chitosan: effects of pH, ionic strength, charge density, chain length and the charge ratio.

Hyaluronic acid (HA) and chitosan (CH) can form nanoparticles, hydrogels, microspheres, sponges, and films, all with a wide range of biomedical applications. This variety of phases reflects the multiple pathways available to HA/CH complexes. Here, we use turbidimetry, dynamic light scattering, light microscopy and zeta potential measurements to show that the state of the dense phase depends on the molar ratio of HA carboxyl to CH amines, and is strongly dependent on their respective degrees of ionization, α and β.

"Bio-glues" to enhance slipperiness of mucins: improved lubricity and wear resistance of porcine gastric mucin (PGM) layers assisted by mucoadhesion with chitosan.

A synergetic lubricating effect between porcine gastric mucin (PGM) and chitosan based on their mucoadhesive interaction is reported at a hydrophobic interface comprised of self-mated polydimethylsiloxane (PDMS) surfaces. In acidic solution (pH 3.2) and low concentrations (0.

Tunable adsorption of bovine serum albumin by annealed cationic spherical polyelectrolyte brushes.

By combining turbidimetric titration, dynamic light scattering (DLS), and zeta potential methods, we demonstrated that the adsorption of bovine serum albumin (BSA) in annealed cationic spherical polyelectrolyte brushes (SPB) can be controlled by modulating the pH, ionic strength, BSA concentration of the mixed solution, and SPB thickness. The SPB consist of a polystyrene core with a diameter around 80 nm and a dense shell of poly (2-aminoethylmethacrylate hydrochloride) (PAEMH) with a thickness from 10 to 60 nm covalently attached on the core surface. Results revealed the existence of three pH regions, corresponding to (1) adsorption of BSA in SPB, (2) aggregation of SPB induced by BSA adsorption, and (3) desorption of BSA from SPB.

Complexation and coacervation of polyelectrolytes with oppositely charged colloids.

Polyelectrolyte-colloid coacervation could be viewed as a sub-category of complex coacervation, but is unique in (1) retaining the structure and properties of the colloid, and (2) reducing the heterogeneity and configurational complexity of polyelectrolyte-polyelectrolyte (PE-PE) systems. Interest in protein-polyelectrolyte coacervates arises from preservation of biofunctionality; in addition, the geometric and charge isotropy of micelles allows for better comparison with theory, taking into account the central role of colloid charge density. In the context of these two systems, we describe critical conditions for complex formation and for coacervation with regard to colloid and polyelectrolyte charge densities, ionic strength, PE molecular weight (MW), and stoichiometry; and effects of temperature and shear, which are unique to the PE-micelle systems.

Protein specificity of charged sequences in polyanions and heparins.

Long-range electrostatic interactions are generally assigned a subordinate role in the high-affinity binding of proteins by glycosaminoglycans, the most highly charged biopolyelectrolytes. The discovery of high and low sulfation domains in heparan sulfates, however, suggests selectivity via complementarity of their linear sulfation patterns with protein charge patterns. We examined how charge sequences in anionic/nonionic copolymers affect their binding to a protein with prominent charge anisotropy.

Heterogeneity of polyelectrolyte diffusion in polyelectrolyte-protein coacervates: a 1H pulsed field gradient NMR study.

Proton pulsed field gradient (PFG) NMR was used to study the diffusion of poly(diallyldimethylammonium chloride) (PDADMAC) in coacervates formed from this polycation and the protein bovine serum albumin (BSA). Application of high (up to 30 T/m) magnetic field gradients in PFG NMR measurements allowed probing the diffusion of PDADMAC on a length scale of displacements as small as 100 nm in coacervates formed at different pH's and ionic strengths, i.e.

Effect of polyelectrolyte structure on protein-polyelectrolyte coacervates: coacervates of bovine serum albumin with poly(diallyldimethylammonium chloride) versus chitosan.

Electrostatic interactions between synthetic polyelectrolytes and proteins can lead to the formation of dense, macroion-rich liquid phases, with equilibrium microheterogeneities on length scales up to hundreds of nanometers. The effects of pH and ionic strength on the rheological and optical properties of these coacervates indicate microstructures sensitive to protein-polyelectrolyte interactions. We report here on the properties of coacervates obtained for bovine serum albumin (BSA) with the biopolyelectrolyte chitosan and find remarkable differences relative to coacervates obtained for BSA with poly(diallyldimethylammonium chloride) (PDADMAC).

Effect of pore size on adsorption of a polyelectrolyte to porous glass.

The adsorption of quaternized poly(vinylpyridine) (QPVP) on controlled pore glass (CPG) size, over the ionic strength range 0.001-0.5 M was found to display nonmonotonic behavior as a function of pore size.

Effects of polyelectrolyte chain stiffness, charge mobility, and charge sequences on binding to proteins and micelles.

The binding affinities of polyanions for bovine serum albumin in NaCl solutions from I = 0.01-0.6 M, were evaluated on the basis of the pH at the point of incipient binding, converting each such pH(c) value into a critical protein charge Zc.