Preparation and Application of Chitosan-based Polyelectrolyte Complex Materials: An Overview

Chitosan,a renewable,non-toxic,and natural cationic polyelectrolyte,can be combined with many anionic polyelectrolytes(such as sodium alginate,hyaluronic acid,xylan,and gelatin)via electrostatic forces to form chitosan-based polyelectrolyte composites under certain conditions.This review summarizes various methods of preparing chitosan-based polyelectrolyte composites and analyzes their applications in clinical medicine and agriculture,as well as pharmaceutical,tissue,food,environmental,and textile engineering fields.The future development direction and potential of chitosan-based polyelectrolytes are also discussed.

Polyelectrolyte Complexes between Hyperbranched and Linear Polysaccharides: Fucoidan/Chitosan

Polyelectrolyte complexes(PECs)of hyperbranched(HB)and linear polysaccharides are promising as more effective encapsulation agents compared to PECs formed by linear polysaccharides.We investigated the PECs between the HB anionic polysaccharide fucoidan(FUC)and the cationic linear polysaccharide chitosan(CS).The FUC had a molecular weight(MW)of 30×106.The PECs were prepared in three solvents(water,0.01 and 0.1 mol/L acetic acid)with CS of MW of 15,110 and 170 kDa,and deacetylation degrees(DDA)of 70%and 97%.The structures of the PECs and the initial FUC were investigated by multi-angle static and dynamic light scattering.As the FUC contained 18 wt%of—OSO3 groups and 5 wt%of uronic acid units,it was a“strong-weak”copolyanion,so the HB macromolecules of the FUC formed nanogel particles in 0.1 mol/L AcOH and open branched structures in water,as confirmed by the Kratky plots.After mixing the solutions of original components,the PEC structures underwent an equilibration period,the duration of which increased with the MW of CS.As the charge stoichiometry was approached,the PECs shrank;the fractal dimension approached unity,indicating the side-by-side packing of adjacent FUC branches with the help of CS.Secondary aggregation in the vicinity of the charge compensation was hardly observed,as it occurred in a very narrow region.The PEC content at theζ-potential inversion depended on solvents’pH and the DDA of CS.In the extreme case of core-shell PECs in 0.1 mol/L AcOH,obtained by mixing FUC nanogels with the solutions of high MW CS of 97%DDA,the protruding tails of CS formed a positively charged shell in the whole range of FUC content(10 wt%<WFUC<90 wt%).Scanning electron microscopy and atomic force microscopy images of dried samples were discussed in relation to the light scattering results.

Polyelectrolyte complex-based thermochromic hydrogels containing carbonized polymer dots for smart windows with fast response,excellent solar modulation ability,and high durability

Thermochromic smart windows have gained increasing popularity in light modulation and energy management in buildings.However,the fabrication of flexible thermochromic smart windows with high luminous transmittance(Tlum),tailorable critical temperature(τc),strong solar modulation ability(ΔTsol),and long-term durability remains a huge challenge.In this study,hydrogel-based thermochromic smart windows are fabricated by sandwiching thermochromic hydrogels of polyallylamine hydrochloride,polyacrylic acid,and carbonized polymer dots(CPDs)complexes between two pieces of transparent substrates.Benefiting from the incorporation of nanosized CPDs,the thermochromic hydrogel has an ultrahigh Tlum of~98.7%,a desirableτc of~24.2℃,aΔTsol of~89.3%and a rapid transition time of~3 s from opaque state to transparent state.Moreover,the thermochromic hydrogel exhibits excellent anti-freezing ability,tight adhesion toward various substrates,and excellent self-healing capability.The self-healing capability enables the fabrication of large-area smart windows by welding multiple hydrogel pieces.The smart windows retain their original thermochromic properties after being stored under ambient conditions for at least 147 days or undergoing 10,000 uninterrupted heating/cooling cycles.The model houses with smart windows can achieve a temperature reduction of 9.2℃,demonstrating the excellent indoor temperature modulation performance of the smart windows.

Carbon Fibers Decorated by Polyelectrolyte Complexes toward Their Epoxy Resin Composites with High Fire Safety

The achievement of both robust fire-safety and mechanical properties is of vital requirement for carbon fiber （CF） composites. To this end, a facile interracial strategy for fabricating flame-retardant carbon fibers decorated by bio-based polyelectrolyte complexes （PEC） consisting of chitosan （CH） and ammonium polyphosphate （APP） was developed, and its corresponding fire-retarded epoxy resin composites （EP/（PEC@CF）） without any other additional flame retardants were prepared. The decorated CFs were characterized by SEM- EDX, XPS and XRD, indicating that the flame-retardant PEC coating was successfully constructed on the surface of CF. Thanks to the nitrogen- and phosphorous-containing PEC, the resulting composites exhibited excellent flame retardancy as the limiting oxygen index （LOI） increased from 31.0% of EP/CF to 40.5% and UL-94 V-0 rating was achieved with only 8.1 wt% PEC. EP/（PEC8.1@CF） also performed well in cone calorimetry with the decrease of peak-heat release rate （PHRR） and smoke production rate （SPR） by 50.0% and 30.4%, respectively, and the value of fire growth rate （FIGRA） was also reduced to 3.41 kW·m-2- s-1 from 4.84 kW· m-2· s-1, suggesting a considerably enhanced fire safety. Furthermore, SEM images of the burning residues revealed that the PEC coating exhibited the dominant flame-retardant activity in condensed phase via the formation of compact phosphorus-rich char. In addition, the impact strength of the composite was improved, together with no obvious deterioration of flexural properties and glass transition temperature. Taking advantage of the features, the PEC-decorated carbon fibers and the relevant composites fabricated by the cost-effective and facile strategy would bring more chances for widespread applications.

POLYMER COLLOIDS FORMED BY POLYELECTROLYTE COMPLEXATION OF VINYL POLYMERS AND POLYSACCHARIDES IN AQUEOUS SOLUTION

The polyelectrolyte complex formed from the polyanion and polycation was studied by turbidimetry, static and electrophoretic light scattering, and elementary analysis. Sodium salts of polyacrylate （PA） and heparin （Hep） were chosen as the polyanion, and hydrochloric salts of poly（vinyl amine） （PVA） and chitosan （Chts） as the polycation. Although these vinyl polymers and polysaccharides have remarkably different backbone chemical structures and linear charge densities, all the four combinations PA-PVA, PA-Chts, Hep-PVA, and Hep-Chts provide almost stoichiometric polyelectrolyte complexes which are slightly charged owing to the adsorption of the excess polyelectrolyte component onto the neutral complex. The charges stabilize the complex colloids in aqueous solution of a non-stoichiometric mixture, and the aggregation number of the complex colloids increases with approaching to the stoichiometric mixing ratio. The mixing ratio dependence of the aggregation number for the four complexes is explained by the model proposed in the previous study.

Fabrication of channeled scaffolds through polyelectrolyte complex (PEC) printed sacrificial templates for tissue formation

One of the pivotal factors that limit the clinical translation of tissue engineering is the inability to create large volume and complex three-dimensional (3D) tissues, mainly due to the lack of long-range mass transport with many current scaffolds. Here we present a simple yet robust sacrificial strategy to create hierarchical and per-fusable microchannel networks within versatile scaffolds via the combination of embedded 3D printing (EB3DP), tunable polyelectrolyte complexes (PEC), and casting methods. The sacrificial templates of PEC filaments (diameter from 120 to 500 μm) with arbitrary 3D configurations were fabricated by EB3DP and then incorpo-rated into various castable matrices (e.g., hydrogels, organic solutions, meltable polymers, etc.). Rapid disso-lution of PEC templates within a 2.00 M potassium bromide aqueous solution led to the high fidelity formation of interconnected channels for free mass exchange. The efficacy of such channeled scaffolds for in vitro tissue formation was demonstrated with mouse fibroblasts, showing continuous cell proliferation and ECM deposition. Subcutaneous implantation of channeled silk fibroin (SF) scaffolds with a porosity of 76% could lead to tissue ingrowth as high as 53% in contrast to 5% for those non-channeled controls after 4 weeks. Both histological and immunofluorescence analyses demonstrated that such channeled scaffolds promoted cellularization, vasculari-zation, and host integration along with immunoregulation.

The correlation between thermally induced precipitateto-coacervate transition and glass transition in a polyelectrolyte-bolaamphiphile complex

The precipitate and the coacervate are two aggregated states in the polyelectrolyte complexes(PECs).The precipitate-to-coacervate transition and glass transition in PECs have been widely reported in the past.In many cases,the two phenomena are studied independently,although both of them are apparently affected by water and small ions.Here,utilizing a PEC system consisting of poly(acrylic acid)(PAA)and a cationic bolaamphiphile(DBON),we explore the states of PECs as a function of salt,temperature,and the molecular weight of PAAs.By a combination of microscopic observation,time-resolved fluorescence measurements,and differential scanning calorimetry,we identify salt/temperature driven precipitate-to-coacervate transitions of the complexes.The thermally induced morphology transformation from the precipitate to coacervate occurs around the glass transition temperature,indicating a strong correlation between the two processes.As the molecular weight of the PAA increases,the thermal transition temperature becomes higher.This finding offers new insights on the mechanistic interactions that dictate the aggregated states of PECs.Based on the photothermal effect of DBON,we also develop a UV light-induced strategy to mediate the precipitate-to-coacervate transition,providing a fantastic platform to create functional PEC materials.

Self-stabilized chitosan and its complexes with carboxymethyl starch as excipients in drug delivery

This study focuses on the behavior of chitosan(CHI)and its polyelectrolyte complexes with carboxymethyl starch(CMS)used as monolithic matrices with acetaminophen as drug tracer.Two different chitosan grades were tested alone or associated in various ratios with CMS as excipients for tablets obtained by direct compression.The degree of deacetylation(DDA)of CHI,estimated from 1H NMR and FTIR data,was correlated with X-ray diffraction and scanning electron microscopy(SEM)to evaluate structural organization of the monolithic matrices.In vitro drug dissolution assays showed major differences in CHI kinetic profiles between tablets exposed to acidic medium for 2h(to mimick gastric passage)prior to dissolution in simulated intestinal fluid(SIF),and those administered directly to SIF.Prior exposure to acidic SGF conducted to longer dissolution profiles(release completed after 16 h)and preservation of tablet shape,whereas tablets directly incubated in SIF were rapidly disintegrated.The improved properties of chitosan matrices exposed to SGF may be related to an outer compact coating layer(visible in SEM).The effect of self-stabilization of chitosan in acidic medium was compared to that due to formation of polyelectrolyte complexes(PEC)in co-processed polymeric systems(CHI:CMS).The self-formed membrane following exposure to gastric acidity appears to help maintaining tablet integrity and allows higher drug loading,recommending CHI and its complexes with CMS as excipients for drug delivery.

Shear-responsive peptide/siRNA complexes as lung-targeting gene vectors

Particles administrated intravenously will pass through the pulmonary capillary network before being distributed to the body.Therefore,fabrication of vectors sensitive to blood shear and active with blood components should be a practical approach to develop lung-targe ting gene carriers self-regulated by circulatory system.In this work,we designed a series of cationic peptides with the same charge density but varying hydrophobicity and capacity to form hydrogen bonds,and investigated their ability to form co mplexes with siRNA,the behaviours of peptide/siRNA complexes in the presence of serum under shear,and the lung-targeting efficacy of the complexes regulated by blood.The hydrophobic interaction co ntrols the complexation between peptide and siRNA,while the hydrogen bonds are responsible for the binding of peptides to the serum components in blood.In vivo tests show that all the peptide/siRNA complexes can accumulate in lung.However,only the complexes that exhibit weak interaction with serum components and can be broken down by shear avoid the inflammation and death caused by pulmonary embolism.Moreover,the peptide with strong hydrophobicity can retain siRNA in lung without early release of the cargo.Our study provides a step toward the development of adaptive gene carriers under the regulation of circulatory system.

Complexation between DNA and Peptides with Precisely Controlled Charge Density and Distribution

Using three designed peptides with precisely-controlled charge density and three types of DNAs with different length and flexibility, the effect of charge density on the formation of PEC was studied. Highly charged（KKKK）5 interacts strongly with 21 bp ds DNA to form large complex, followed by precipitation; while the medium charged（KGKG）5 only form complex with 21 bp ds DNA at proper ＋/- charge ratios; and no prominent complex between weakly charged（KGGG）5 and 21 bp ds DNA is observed at the same conditions. Similar trend is observed when the peptides form complex with 2000 bp DNA or 21 nt ssD NA. It is also found that the complex formed by adding peptide to DNA is in random coil conformation, but the complex prepared by the inverse order is in molten globule state. Re-dissolution of the complex occurs only when DNA is added to peptides with similar or shorter length.