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The precise and effective detection of neurotransmitters (NTs) is crucial for clinical investigation of neuronal processes, and timely monitoring of NT-related chronic diseases. However, sensitive detection of specific NT with unprecedented selectivity is highly challenging due to similarities in chemical and electronic structures of various interfering neurochemicals. Herein, an anionic conjugated polyelectrolyte Poly[(9,9-bis(4'-sulfonatobutyl)fluorene-co-alt-1,4-phenylene) sodium], PFPS was rationally designed and synthesized for amplified detection and point-of-care (PoC) determination of monoamine neurotransmitter, serotonin (5-Hydroxy tryptamine or 5-HT, also diagnostic biomarker of carcinoid tumor) in human blood plasma. The PFPS displayed a remarkable sensing response with an exceptionally high fluorescence quenching constant of 1.14×10 5  M -1 and an ultralow detection limit of 0.67 μM or 0.142 ppm, much below the clinical range. Furthermore, a smartphone-enabled portable platform was constructed for real-time onsite detection of 5-HT by quantification of visual fluorescence response of PFPS into RGB values using a color recognizer android application. The smartphone platform could be readily applied for convenient, non-invasive PoC testing of 5-HT levels in complex biological fluids accurately and is expected to revolutionize clinical diagnosis and personalized health care devices., (© 2024 Wiley-VCH GmbH.)

Sodium alginate (SA) and chito oligosaccharide (COS) are widely used food additives in the food industry, and exploring their interaction to form polyelectrolyte complexes (PECs) may provide insights into food development. In the present study, the effects of viscosity-average molecular weight (M v ) and relative amounts of SA on the formation of sodium alginate/chito oligosaccharide polyelectrolyte (SCP) complexes were investigated. The results showed that the electrostatic interaction between -COOH and -NH 2 and the hydrogen bonding between OH, were attributed to the formation of the SCP complexes. Then the formation and properties of SCP complexes were greatly dependent on the M v and the relative amount of SA. SA with M v of ≥2.16 × 10 6  Da could form spherical SCP complexes, while the SA/COS ratio (w/w) ≥ 0.8 was not conducive to the formation of SCP complexes. Moreover, the SCP complexes were more stable in the gastric environment than in the intestinal condition. In addition, 1.73 × 10 7  Da was the optimal M v of SA for SCP complexes formation. This study contributed to a comprehensive understanding of the interaction between SA and COS, and shed light on the potential application of SA and COS formulation to develop new food products., Competing Interests: Declaration of competing interest The authors declare that we do not have any potential conflicts of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polyoxometalates (POMs), molecular metal oxide anions, are inorganic clusters with promising antiviral activity. Herein we report increased anti-HIV-1 activity of a POM when electrostatically combined with organic counter-cations. To this end, Keggin-type cerium tungstate POMs have been combined with organic methyl-caffeinium (Caf) cations, and their cytotoxicity, antiviral activity and mode of action have been studied. The novel compound, Caf 4 K[β 2 -CeSiW 11 O 39 ]×H 2 O, exhibits sub-nanomolar antiviral activity and inhibits HIV-1 infectivity by acting on an early step of the viral infection cycle. This work demonstrates that combination of POM anions and organic bioactive cations can be a powerful new strategy to increase antiviral activity of these inorganic compounds., (© 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

We reported an efficient multicomponent polyannulation for in situ generation of heteroaromatic hyperbranched polyelectrolytes by using readily accessible internal diynes and low-cost, commercially available arylnitriles, NaSbF 6 , and H 2 O/AcOH. The polymers were obtained in excellent yields (up to 99 %) with extraordinary high molecular weights (M w up to 1.011×10 6 ) and low polydispersity indices. The resulting polymers showed good processibility and high quantum yields with tunable emission in the solid state, making them ideal materials for highly ordered fluorescent photopatterning. These hyperbranched polyelectrolytes also possessed strong ability to generate reactive oxygen species, which allowed their applications in efficient bacterial killing and customizable photodynamic patterning of living organisms in a simple and cost-effective way., (© 2021 Wiley-VCH GmbH.)

Microbial keratitis (MK) is a vision-threatening disease and the fourth leading cause of blindness worldwide. In this work, we aim to develop moxifloxacin (MXN)-loaded chitosan-based cationic mucoadhesive polyelectrolyte nanocapsules (PENs) for the effective treatment of MK. PENs were formulated by polyelectrolyte complex coacervation method and characterized for their particle size, surface charge, morphology, mucoadhesive property, in-vitro and ex-vivo release, ocular tolerance, and antimicrobial efficacy studies. The pharmacodynamic study was conducted on rabbit eye model of induced keratitis and it is compared with marketed formulation (MF). Developed PENs showed the size range from 230.7 ± 0.64 to 249.0 ± 0.49 nm and positive surface charge, spherical shape along with appropriate physico-chemical parameters. Both in-vitro and ex-vivo examination concludes that PENs having more efficiency in sustained release of MXN compared to MF. Ocular irritation studies demonstrated that no corneal damage or ocular irritation. The in-vivo study proved that the anti-bacterial efficacy of PENs was improved when compared with MF. These results suggested that PENs are a feasible choice for MK therapy because of their ability to enhance ocular retention of loaded MXN through interaction with the corneal surface of the mucous membrane.

Strategies for incorporating water-insoluble photosensitisers (PS) in drug delivery systems have been extensively studied. In this work, we evaluate the formation, characterisation, drug sorption studies, and cytotoxicity of chitosan (CHT)/chondroitin sulphate (CS) polyelectrolyte complexes (PECs) coated with polystyrene-block-poly(acrylic acid) (PS-b-PAA) nanoparticles (NPs) loaded with chloroaluminum phthalocyanine (AlClPc). The PECs were characterised by infrared spectroscopy (FTIR), differential scanning calorimetric (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The PS-b-PAA NPs on the PEC surface was confirmed by scanning electron microscopy (SEM). Additionally, optical images distinguished the PEC structures containing PS-b-PAA or PS-b-PAA/AlClPc from the unloaded PEC. Kinetic and equilibrium studies investigate the sorption capacity of the PEC/PS-b-PAA toward AlClPc. The encapsulation efficiency reached 95% at 190 μg mL -1 AlClPc after only 15 min. The Brunauer-Emmett-Teller (BET) isotherm and pseudo-second-order kinetic fitted well to the experimental data. The PS-b-PAA NPs on the PEC surfaces increase the AlClPc bioavailability and the PEC structure stabilizes the PS-b-PAA/AlClPc nanostructures. The materials were cytocompatible upon healthy VERO (kidney epithelial cells), and cytotoxic against colorectal cancerous cells (HT-29 cells). For the first time, we associate PS-b-PAA/AlClPc with a hydrophilic and cytocompatible polysaccharide matrix. We suggest the use of these materials in strategies to treat cancer by using photodynamic therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cationic, π-conjugated oligo-/polyelectrolytes (CCOEs/CCPEs) have shown great potential as antimicrobial materials to fight against antibiotic resistance. In this work, we treated wild-type and ampicillin-resistant (amp-resistant) Escherichia coli ( E. coli ) with a promising cationic, π-conjugated polyelectrolyte (P1) with a phenylene-based backbone and investigated the resulting morphological, mechanical, and compositional changes of the outer membrane of bacteria in great detail. The cationic quaternary amine groups of P1 led to electrostatic interactions with negatively charged moieties within the outer membrane of bacteria. Using atomic force microscopy (AFM), high-resolution transmission electron microscopy (TEM), we showed that due to this treatment, the bacterial outer membrane became rougher, decreased in stiffness/elastic modulus (AFM nanoindentation), formed blebs, and released vesicles near the cells. These evidences, in addition to increased staining of the P1-treated cell membrane by lipophilic dye Nile Red (confocal laser scanning microscopy (CLSM)), suggested loosening/disruption of packing of the outer cell envelope and release and exposure of lipid-based components. Lipidomics and fatty acid analysis confirmed a significant loss of phosphate-based outer membrane lipids and fatty acids, some of which are critically needed to maintain cell wall integrity and mechanical strength. Lipidomics and UV-vis analysis also confirmed that the extracellular vesicles released upon treatment (AFM) are composed of lipids and cationic P1. Such surface alterations (vesicle/bleb formation) and release of lipids/fatty acids upon treatment were effective enough to inhibit further growth of E. coli cells without completely disintegrating the cells and have been known as a defense mechanism of the cells against cationic antimicrobial agents.

Antimicrobial surfaces are important in medical, clinical, and industrial applications, where bacterial infection and biofouling may constitute a serious threat to human health. Conventional approaches against bacteria involve coating the surface with antibiotics, cytotoxic polymers, or metal particles. However, these types of functionalization have a limited lifetime and pose concerns in terms of leaching and degradation of the coating. Thus, there is a great interest in developing long-lasting and non-leaching bactericidal surfaces. To obtain a bactericidal surface, we combine micro and nanoscale patterning of borosilicate glass surfaces by ultrashort pulsed laser irradiation and a non-leaching layer-by-layer polyelectrolyte modification of the surface. The combination of surface structure and surface charge results in an enhanced bactericidal effect against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria. The laser patterning and the layer-by-layer modification are environmentally friendly processes that are applicable to a wide variety of materials, which makes this method uniquely suited for fundamental studies of bacteria-surface interactions and paves the way for its applications in a variety of fields, such as in hygiene products and medical devices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

There are still some key problems in the process of the flame retardant treatment of poly vinyl alcohol (PVA): poor compatibility, deteriorating mechanical properties and potential toxicity to human health and environment. To solve these issues, a green and eco-friendly bio-based polyelectrolyte complex (PEC) formed by chitosan and phytic acid was designed to enhance the flame retardant and mechanical properties of PVA by a facile ultrasonic-assisted solution blending method. Moreover, the mechanical and flame retardant properties could be regulated by varying the ratio of each component in the PEC. Thermogravimetric analysis (TGA) indicated that after the introduction of PEC, PVA/PEC composites maintained better thermal stability and char formation ability. Besides, when the addition of PEC reached 20 wt%, the limited oxygen index (LOI) value of cured PVA increased from 18% to 25.9%, 30.8% and 35.6% for PVA/20(2 : 1) PEC, PVA/20(1 : 2) PEC and PVA/20(1 : 8) PEC, respectively. Moreover, UL-94 V-0 rating was achieved except for the PVA/20(2 : 1) PEC. Compared with pure PVA, the peak heat release rate (pHRR) and the total heat release (THR) of PVA/20(1 : 8) PEC demonstrated a sharp decrease by 69.9% and 45.5%, respectively, in the microscale combustion calorimeter measurements (MCC). These results indicate that PEC can endow PVA with excellent flame retardancy. Furthermore, the microscopic investigations on char residues of all samples by scanning electron microscopy, Fourier transform infrared spectra and Raman spectroscopy revealed the possible flame retardant mechanisms in condensed and gaseous phases. In addition, PVA/PEC composites have better mechanical properties owing to their harder backbones of chitosan, formation of phosphonate bonds and the PVA molecular chain movement blocked by PEC. As a result, the facile processing technology and eco-friendly flame retardants are expected to be applied in practice.

A functional monomer carrying a carboxylate and a protected primary ammonium group is synthesized from itaconic acid. When copolymerized with dimethyl acrylamide and 4-methacryloyloxybenzophenone, cross-linkable polyzwitterions are obtained. These are converted to surface-attached polyzwitterion networks by simultaneous UV-triggered C,H insertion reactions. The resulting polyzwitterion-coated substrates were studied by surface plasmon resonance spectroscopy measurements, ζ potential and various biological assays. They were (expectedly) protein repellent, yet at the same time (and unexpectedly) cell-adhesive and antimicrobially active. This was attributed to stimulus-responsiveness of the polyzwitterion (confirmed by the ζ potential measurements), which enables charge adjustment at different pH values. When protonated, the polyzwitterions become amphiphilic polycations and, in this state, kill bacteria upon contact like their parent structures (polymer-based synthetic mimics of antimicrobial peptides, SMAMPs).

Hypothesis: Flocculation performance using polyelectrolytes is influenced by critical design parameters including molecular weight, amount and sign of the ionic charge, and polymer architecture. It is expected that systematic variation of these characteristics will impact not only flocculation efficiency (FE) achieved but that charge density and architecture, specifically, can alter the flocculation mechanism. Therefore, it should be possible to tune these design parameters for a desired flocculation application., Experiments: Cationic-neutral and polyampholytic copolymers, exhibiting a range of molecular weights (10 3 -10 6 g/mol), varying charge levels (0-100% cationic, neutral and anionic), and random or block copolymer architecture, were applied to dilute suspensions of silica microparticles (control) and Chlorella vulgaris. FE and zeta potential values were determined over a range of flocculant doses to evaluate effectiveness and mechanism achieved., Findings: These different classes of copolymers provide specific benefits for flocculation, with many achieving >95% flocculation. Block copolymer flocculants exhibit a proposed, dominant bridging mechanism, therefore reducing flocculant dosage required for effective flocculation when compared to analogous random copolymer flocculants. Polyampholytic copolymers applied to C. vulgaris generally exhibited a bridging mechanism and increased FE compared to equivalent cationic-neutral copolymers, indicating a benefit of the anionic component on a more, complex, diversely charged suspension., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Vitamin C (VC) is an indispensable nutrient for human health. However, poor chemical stability in gastric environment restricts its full assimilation by intestine. It is important to construct a safe carrier that can protect VC from the gastric fluid and sustainably release it in intestine. Herein, we designed a novel polyelectrolyte complex (PEC) hydrogel through self-assembly of salecan and chitosan. PEC structure formed by electrostatic interactions was confirmed by FT-IR, XRD, XPS and TGA. Their swelling, morphology, rheology, cytocompatibility and biodegradation were well investigated. In particular, VC released in a controlled and pH-dependent manner. The release amount in simulated intestinal fluid (SIF) was significantly higher than simulated gastric fluid (SGF), and can be maintained at high level in blood after 6 h. Release mechanism agreed well with Ritger-Peppas model. The purpose of this study was to develop a smart nutrient delivery platform for targeted release of VC in intestinal condition., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Polyelectrolyte multilayers composed of pharmaceutical grade fucoidan and chitosan have been assembled and studied in terms of their response to physiological solution conditions and the presence of lysozyme. The influence of phosphate buffered saline (PBS) solution on the multilayer was interrogated using attenuated total reflectance (ATR) Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM). The combination of the techniques reveal that the polyelectrolyte multilayers swell when exposed to PBS after build-up and may include a small degree of mass loss as the film swells. The degree of swelling was influenced by the terminating layer of the multilayer. Upon exposure to lysozyme, it was observed that some deswelling occurred, as the enzyme adsorbed onto and permeated into the multilayer. The behaviour of the multilayer as a potential reservoir for lysozyme contrasts with the interaction with bovine serum albumin, which did not penetrate into the multilayer, indicating either exclusion by size or due to the overall net negative charge of the film., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Polyelectrolyte multilayer (PEC) films of sodium alginate (Na-Alg) and poly(4-vinylpyridine) (P 4 VP) were prepared and were loaded with an antibacterial agent, ciprofloxacin HCl (CIP.HCl) aiming to design new hydrophilic films with controlled physicochemical properties and drug release behaviour that may find application as components of transdermal drug delivery systems. The PEC films were characterized by SEM, XRD, TGA, AFM and FTIR spectroscopy. The hydrophilicity of the PEC films was examined by using contact angle measurement. The number of layers and the nature of the outer layer affect the physicochemical characteristics, CIP.HCl loading and release behaviour of the films. The three layer film PEC-3, which is composed of Na-Alg outer layer deposited on a P 4 VP/Na-Alg double layer, is characterized by the lowest roughness (Rq = 16.3 nm) and the most hydrophilic surface with a contact angle value of 38.1° among all other films. Its crystallinity index is 0.36, and starts to degrade at 195 °C. It exhibits 130-135% equilibrium swelling capacity in acid buffer and water respectively. PEC-3 is the film with the highest drug loading capacity and drug loading efficiency values of 3.51% and 87% respectively. A cumulative drug release of 65% is obtained from PEC-3 within 24 h in pH = 1.2 buffer solution., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Injectable shear-thinning hydrogels can be prepared by the non-covalent interactions between hydrophilic polymers. Although electrostatic force is a typical non-covalent interaction, direct mixing of two oppositely charged polyelectrolytes usually leads to a complex coacervate rather than an injectable hydrogel. Herein, a facile approach is proposed to prepare a shear-thinning hydrogel by nanoengineering of polyelectrolytes. Nanosized cationic micelles with electroneutral shells were prepared by mixing methoxyl poly(ethylene glycol)-block-poly(ε-caprolactone) and poly(ε-caprolactone)-block-poly(hexamethylene guanidine) hydrochloride-block-poly(ε-caprolactone) in an aqueous solution. When sodium carboxymethyl cellulose was added into the micellar solution, the outer poly(ethylene glycol) shell of mixed micelles prevented the instant electrostatic interaction between poly(hexamethylene guanidine) hydrochloride segments and sodium carboxymethyl cellulose, resulting in a homogenous shear-thinning electrostatic (STES) hydrogel. Because of the cationic poly(hexamethylene guanidine) hydrochloride segments, this hydrogel exhibits strong antibacterial activity against both Gram-positive and Gram-negative bacteria. Furthermore, the poly(ε-caprolactone) core of the mixed micelles can efficiently encapsulate a hydrophobic drug. In this work, curcumin-loaded STES hydrogel prepared by this method was used as wound dressing material that can promote wound healing even in infected wounds by further reducing bacterial infection via releasing curcumin. The present study provides a facile strategy to prepare shear-thinning antibacterial hydrogels from polyelectrolytes, which has great potential in biomedical application.

Polymer-based CO2 selective membranes offer an energy efficient method to separate CO2 from flue gas. `Top-down' polyelectrolytes represent a particularly interesting class of polymer materials based on their vast synthetic flexibility, tuneable interaction with gas molecules, ease of processability into thin films, and commercial availability of precursors. Recent developments in their synthesis and processing are reviewed herein. The four main groups of post-synthetically modified polyelectrolytes discern ionised neutral polymers, cation and anion functionalised polymers, and methacrylate-derived polyelectrolytes. These polyelectrolytes differentiate according to the origin and chemical structure of the precursor polymer. Polyelectrolytes are mostly processed into thin-film composite (TFC) membranes using physical and chemical layer deposition techniques such as solvent-casting, Langmuir-Blodgett, Layer-by-Layer, and chemical grafting. While solvent-casting allows manufacturing commercially competitive TFC membranes, other methods should still mature to become cost-efficient for large-scale application. Many post-synthetically modified polyelectrolytes exhibit outstanding selectivity for CO2 and some overcome the Robeson plot for CO2/N2 separation. However, their CO2 permeance remain low with only grafted and solvent-casted films being able to approach the industrially relevant performance parameters. The development of polyelectrolyte-based membranes for CO2 separation should direct further efforts at promoting the CO2 transport rates while maintaining high selectivities with additional emphasis on environmentally sourced precursor polymers.

To overcome the high relapse rate of multiple myeloma (MM), a drug delivery coating for functionalization of bone substitution materials (BSM) is reported based on adhesive, catechol-containing and stimuli-responsive polyelectrolyte complexes (PECs). This system is designed to deliver the MM drug bortezomib (BZM) directly to the anatomical site of action. To establish a gradual BZM release, the naturally occurring caffeic acid (CA) is coupled oxidatively to form poly(caffeic acid) (PCA), which is used as a polyanion for complexation. The catechol functionalities within the PCA are particularly suitable to form esters with the boronic acid group of the BZM, which are then cleaved in the body fluid to administer the drug. To achieve a more thorough control of the release, the thermoresponsive poly( N -isoproplyacrylamide- co -dimethylaminoethylmethacrylate) (P(NIPAM- co -DMAEMA)) was used as a polycation. Using turbidity measurements, it was proven that the lower critical solution temperature (LCST) character of this polymer was transferred to the PECs. Further special temperature dependent attenuated total reflection infrared spectroscopy (ATR-FTIR) showed that coatings formed by PEC immobilization exhibit a similar thermoresponsive performance. By loading the coatings with BZM and studying the release in a model system, via UV/Vis it was observed, that both aims, the retardation and the stimuli control of the release, were achieved.

This work presents a salt-responsive interpenetrating network (IPN) hydrogel with effective antimicrobial properties and surface regeneration. The hydrogels were engineered using the double network strategy to form loosely cross-linked zwitterionic poly(sulfobetaine vinylimidazole) (pSBVI) networks into the highly cross-linked cationic poly((trimethylamino)ethyl methacrylate chloride) (pTMAEMA) framework via photopolymerization. The pTMAEMA/pSBVI hydrogel has strong mechanical properties, with a fracture stress 120× higher than single network pTMAEMA hydrogel. In addition, there is inverse correlation between elastic modulus and elastic strain of pTMAEMA/pSBVI hydrogels as a function of ionic strength. The cationic pTMAEMA and zwitterionic pSBVI show opposite swelling behaviors in salt solutions due to the polyelectrolyte effect and antipolyelectrolyte effect. Therefore, the pTMAEMA/pSBVI hydrogel elicits a significant interfacial transition in solutions with different ionic strengths. The IPN hydrogels have switchable lubrication and optical transmittance between deionized water and 1.0 M NaCl solution. The protein adsorption tests further confirmed the switchable interface of salt-responsive IPN hydrogels. In addition, bacterial attachment test on pTMAEMA/pSBVI hydrogels with Staphylococcus epidermidis ( S. epidermidis ) and Escherichia coli ( E. coli ) show bacterial killing rates of the IPN hydrogel over 80% for S. epidermidis and 90% for E. coli after incubating the hydrogels in the bacterial solutions for 24 h. The bacterial release rate from the IPN hydrogel reached 96% after washing with 1.0 M NaCl solution. Furthermore, the excellent reusability of the pTMAEMA/pSBVI hydrogels was demonstrated by the high bacterial killing and bacterial release rates after five kill/release cycles. The work presents a new stimuli-responsive IPN hydrogel with structural modulation, tunable antimicrobial properties, and surface regeneration by ionic strength. Integrating two salt-responsive polymers with mutually independent actions into a single material provides a new direction for smart materials with potential medical and industrial applications.

Polyelectrolytes play an important role in both natural biological systems and human society, and their synthesis, functional exploration, and profound application are thus essential for biomimicry and creating new materials. In this study, we developed an efficient synthetic methodology for in situ generation of azonia-containing polyelectrolytes in a one-pot manner by using readily accessible nonionic reactant in the presence of commercially available cheap ionic species. The resulting polyelectrolytes are emissive in the solid state and can readily form luminescent photopatterns with different colors. The azonia-containing polyelectrolytes possess extraordinary potency of reactive oxygen species (ROS) generation, enabling them to impressively kill methicillin-resistant Staphylococcus aureus (MRSA), a drug resistant superbug, both in vitro and in vivo .

Polyelectrolytes (PELs) - polymers with charged repeat units - have emerged as a useful class of polymers for biomedical applications due to their high aqueous solubility, low aggregation propensity and the opportunity they afford for polyvalent interactions with surfaces. Biodegradability and biocompatibility of PELs are important prerequisites for their utilization in in vivo applications. PELs that can be chemically functionalized with ease prove advantageous for creating diverse biomaterials. Polyaspartic acid (PASA) is a modular and biocompatible synthetic PEL that has all these features. It also shows many positive biomedical attributes such as bone-tissue targeting, muco-adhesive behavior and extended blood circulation time. Cationic PELs derived from PASA are rapidly internalized by mammalian and bacterial cells, and hence have immense utility in therapeutic delivery applications. Polyelectrolyte complexes (PECs) and multilayers (PEMs) formed from PASA PELs have further expanded their biomedical utility. This mini-review highlights some recent literature examples of unique biomedical applications of PELs, PECs and PEMs prepared through the molecular engineering of PASA. It discusses biomineralization modulators, anti-mycobacterial agents, underwater adhesives, mucoadhesive drug and gene delivery agents, and cell encapsulants fabricated using PASA derived PELs.

The aim of this work was to examine the formation and properties of a novel polyelectrolyte complex of drug carrier system for the delivery of doxorubicin (DOX), which consists of hyaluronic acid (HA) coated hydrophobically modified chitosan (CS). Various batches of polyelectrolyte complexes with the molar ratio of deoxycholic acid (DCA) and chitosan (CS) of 0.1, 0.2, 0.3 were prepared, and were termed as CS-DCA 10 , CS-DCA 20 , and CS-DCA 30 respectively. The samples were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), nuclear magnetic resonance hydrogen spectrum ( 1 H NMR) and dynamic light scattering (DLS). Particle sizes of synthesized polyelectrolyte complex nanoparticles (PCNs) were found to be in the range of 280-310 nm, larger than those of uncoated nanoparticles (~150 nm). The PCNs have large zeta potentials (about 26 mV) which make them stable and no sizes' change was determined. DOX could be easily incorporated into the PCNs with encapsulation efficiency (56%) and kept a sustained release manner without burst effect when exposed to PBS (pH 7.4) at 37 °C. Overall, these findings confirmed the potential of these PCNs for drug carrier and prolonged and sustained delivery in the bloodstream., (Copyright © 2018. Published by Elsevier B.V.)

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.

1,4,7,10-Tetraazacyclododecane (cyclen) has a unique cyclic structure that endows it with a number of characteristics, including its cationic nature, easy modification and strong coordination ability toward a wide range of cations. Zn 2+ , which can easily coordinate to cyclen, is an essential metal ion for DNA binding. In this report, Zn(ii)-polycations derived from cyclen were studied as non-viral gene delivery vectors. Polycations were synthesized from diglycidyl ethers and cyclen through ring-opening polymerization, and then Zn(ii)-complexes were obtained by reacting the polycations with Zn(NO 3 ) 2 ·6H 2 O. UV absorption and circular dichroism spectra revealed that the Zn(ii)-complexes may induce apparent conformational changes of DNA, while polycations could not. Agarose gel retardation assay demonstrated that although the Zn(ii)-polycations exhibited slightly lower DNA binding ability compared to their polycation counterparts, they showed better DNA release, which might favor the gene transfection process. In vitro transfection results revealed that the coordination of Zn(ii) may dramatically increase the transfection efficiency of the polymers. In addition, almost all polycations and their Zn(ii)-complexes exhibited better serum tolerance than polyethylenimine (PEI), especially Zn-cyclen-HD. Flow cytometry and BSA adsorption experiments also demonstrated the good serum tolerance of the Zn(ii)-polycations. Meanwhile, such materials also exhibited acceptable cytotoxicities at transfection dosages. These results may afford us clues for developing novel non-viral gene vectors with high efficiency and biocompatibility.

A bioinspired zwitterionic polyelectrolyte coating with excellent hydration ability has been regarded as a promising lubricating candidate for modifying artificial joint cartilage surface. In physiological fluids, the ubiquitous proteins play an important role in achieving outstanding boundary lubrication; however, a comprehensive understanding of the hydration lubrication between polyelectrolyte coatings and proteins still remains unclear. In this work, a facile fabrication of ultrasmooth polyelectrolyte coatings was developed via codeposition of synthesized poly(dopamine methacrylamide- co-2-methacryloyloxyethyl phosphorylcholine) (P(DMA- co-MPC)) and dopamine (DA) in a mild condition. Upon optimization of the feeding ratio of P(DMA- co-MPC) and DA, the as-fabricated PDA/P(DMA- co-MPC) coatings exhibit excellent lubricating properties when sliding with each other (friction coefficient μ = 0.036 ± 0.002, ∼2.8 MPa), as well as sliding with a model protein (bovine serum albumin (BSA)) layer (μ = 0.041 ± 0.005, ∼4.8 MPa) in phosphate-buffered saline (PBS, pH 7.4). Intriguingly, the lubrication in both systems shows Amontons-like behaviors: the friction is directly proportional to the applied load but independent of the shear velocity. Moreover, the PDA/P(DMA- co-MPC) coatings could resist the protein fouling (i.e., BSA) in PBS, which is crucial to prevent the surfaces from being contaminated when applied in biological media, thus maintaining their lubricating properties. Our results provide a versatile approach for facilely fabricating polyelectrolyte coatings with superior lubrication properties to both polyelectrolyte coatings and protein surfaces, with useful implications into the development of novel lubricating coatings for bioengineering applications (e.g., artificial joints).

Background: Toxicity of nanomaterials is one of the most important factors limiting their medical application. Evaluation of in vitro nanotoxicity allows for the identification and elimination of most of the toxic materials prior to animal testing. The current knowledge of the possible side effects of biodegradable nanomaterials, such as liposomes and polymeric organic nanoparticles, is limited. Previously, we developed a potential drug delivery system in the form of nanocapsules with polyelectrolyte, biodegradable shells consisting of poly-l-lysine and poly-l-glutamic acid (PGA), formed by the layer-by-layer adsorption technique., Methods: Hemolysis assay, viability tests, flow cytometry analysis of vascular cell adhesion molecule-1 expression on endothelium, analysis of nitric oxide production, measurement of intracellular reactive oxygen species levels, detection of antioxidant enzyme activity, and analysis of DNA damage with comet assay were performed to study the in vitro toxicity of nanocapsules., Results: In this work, we present the results of an in vitro analysis of toxicity of five-layer positively charged poly-l-lysine-terminated nanocapsules (NC5), six-layer negatively charged PGA-terminated nanocapsules (NC6) and five-layer PEGylated nanocapsules (NC5-PEG). PGA and polyethylene glycol (PEG) were used as two different "stealth" polymers. Of all the polyelectrolyte nanocapsules tested for blood compatibility, only cationic NC5 showed acute toxicity toward blood cells, expressed as hemolysis and aggregation. Neither NC6 nor NC5-PEG had proinflammatory activity evaluated through changes in the expression of NF-κB-dependent genes, iNOS and vascular cell adhesion molecule-1, induced oxidative stress, or promoted DNA damage in various cells., Conclusion: Our studies clearly indicate that PGA-coated (negatively charged) and PEGylated polyelectrolyte nanocapsules do not show in vitro toxicity, and their potential as a drug delivery system may be safely studied in vivo., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Membrane-intercalating conjugated oligoelectrolytes (COEs) are emerging as potential alternatives to conventional, yet increasingly ineffective, antibiotics. Three readily accessible COEs, belonging to an unreported series containing a stilbene core, namely D4, D6, and D8, were designed and synthesized so that the hydrophobicity increases with increasing side-chain length. Decreased aqueous solubility correlates with increased uptake by E. coli. The minimum inhibitory concentration (MIC) of D8 is 4 μg mL -1 against both E. coli and E. faecalis, with an effective uptake of 72 %. In contrast, the MIC value of the shortest COE, D4, is 128 μg mL -1 owing to the low cellular uptake of 3 %. These findings demonstrate the application of rational design to generate efficacious antimicrobial COEs that have potential as low-cost antimicrobial agents., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Neutral conjugated tetraarylethenes OFn (n = 1-3) and the corresponding cationic conjugated oligoelectrolytes OFn+ (n = 1-3) with aggregation-induced emission activity have been designed and synthesized using geminal cross-coupling. OFn+ (n = 1-3) feature ion-induced emission in aqueous solution. They are used for lysosomal fluorescence imaging and tracing of lysosome events.

This work investigates the effect of multifunctional poly (N-isopropyl acrylamide/acrylic acid/N-tert-butylacrylamide) [p(NIPAM-AA-NTBA)] ternary polymer on the sedimentation of kaolin clay - a major fraction of oil sands tailings. A series of linear, uncross-linked p(NIPAM), p(NIPAM/AA), and p(NIPAM/AA/NTBM) were synthesized as random copolymers, where all monomer units were randomly arranged along the polymer backbone and connected by covalent bonds. The ternary copolymer, used as a flocculant, exhibited thermo-sensitivity, anionic nature, and hydrophobic association due to NIPAM, AA, and NTBM, respectively. As the ternary polymer is thermosensitive, it undergoes extended to coil-like conformation, i.e. hydrophilic to hydrophobic transition, above its lower critical solution temperature (LCST). The comonomers NIPAM (above LCST) and NTBM help expel water out of sediments due to their hydrophobicity, while AA promotes charge neutralization of the kaolin clay particles. The effect of number average molecular weight, charge density, and concentration of NTBM on settling behavior of kaolin suspension was examined. Settling test at 50 °C resulted in significantly higher settling rates compared to that at room temperature. Further, the quality of water recovered in each experiment was tested in terms of its turbidity. These results indicate that this novel ternary polymer can be employed to enhance the recovery of water from oil sands tailings containing clays., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this study, negatively charged carboxylic curdlan (Cc) bearing a β-1,3-polyglucuronic acid structure was employed to fabricate nanosized polyelectrolyte complexes (PECs) with positively charged chitosan (CS) in aqueous solution as potential carriers for 5-fluorouracil (5Fu) delivery. Nanosized CS/Cc PECs were formed by the addition of 0.5mg/mL solutions of CS and Cc with a mixing ratio of 1:1 (w/w) at pH 3.0. Under optimized conditions, the prepared CS/Cc PECs showed spherical morphology with an average size of about 180nm and a zeta potential of around 41mV. The 5Fu drug was incorporated into the nanosized CS/Cc PECs and showed excellent encapsulation efficiency (86.47%) and loading content (10.81%). The drug release data in vitro indicated that the nanosized CS/Cc PECs are promising carriers for the sustained release of 5Fu with an anomalous transport mechanism following the Ritger-Peppas model. Besides, the CS/Cc PECs exhibited low cytotoxic activity against SPCA-1 and HeLa cell lines in vitro. This finding suggested that the development of the nanosized CS/Cc PECs offered great promise as an antitumor drug platform., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A novel humic acid and polyquaternium-10 polyelectrolyte complex (PEC) was synthesized utilizing two methods and the solubility and permeability of efavirenz (EFV) were established. Complexation-precipitation and extrusion-spheronization were used to synthesize and compare the drug-loaded PECs. The chemical integrity, thermo-mechanical differences, and morphology between the drug-loaded PECs produced by the two methods were assessed by attenuated total reflectance-Fourier transform infrared, differential scanning calorimetry, and SEM. The extent of drug solubilization was determined using the saturation solubility test while the biocompatibility of both PECs was confirmed by cytotoxicity studies on human adenocarcinoma cells (caco2). Bio-relevant media was used for the solubility and permeability analysis of the optimized PEC formulations for accurate assessment of formulation performance. Ritonavir (RTV) was loaded into the optimized formulation to further corroborate the impact of the PEC on the solubility and permeability properties of a poorly soluble and poorly permeable drug. The optimized EFV-loaded PEC and the RTV-loaded PEC exhibited 14.16 ± 2.81% and 4.39 ± 0.57% increase in solubility, respectively. Both PECs were compared to currently marketed formulations. Intestinal permeation results revealed an enhancement of 61.24 ± 6.92% for EFV and 38.78 ± 0.50% for RTV. Although both fabrication methods produced PECs that enhanced the solubility and permeability of the model Biopharmaceutics Classification System Class II and IV drugs, extrusion-spheronization was selected as most optimal based on the higher solubility and permeability improvement and the impact on caco2 cell viability.

The layer-by-layer assembly of polyelectrolyte multilayers (PEMs) from natural or synthetic polyelectrolytes constitutes a very versatile and simple strategy to modify surfaces and modulate cell behavior. PEMs assembled from natural polyelectrolytes are very appealing for biological and medical applications due to their high biocompatibility. However, PEMs from natural polyelectrolytes display poor cell adhesion as they are soft materials with an elasticity modulus of a few kilopascal. In this report, the authors present results on the modulation of cell adhesion of different immortalized cell lines by PEMs. Two strategies are employed to vary cell adhesion: (1) a heterogeneous polyelectrolyte multilayer is assembled employing a rigid bottom block including a synthetic polyelectrolyte with a soft upper block of natural polyelectrolytes and (2) polyelectrolyte multilayers from natural polyelectrolytes are thermally annealed after assembly. The physicochemical characteristics of the PEMs change upon thermal treatment. Depending on the composition of the polyelectrolyte multilayer, cell adhesion may be enhanced or reduced. Based on the impact on PEM properties and cell adhesion caused by thermal annealing, a temperature gradient is applied to a PEM of poly-l-lysine/alginate to induce a spatial variation of PEM properties, resulting in a gradient in cell adhesion. The strategies shown here can be employed as simple alternatives to tailor PEM properties by means of fully biocompatible procedures.

Three cationic conjugated polyelectrolytes (CPEs) with a common poly(p-phenylene ethynylene) backbone and different galactose-containing side chains were designed and synthesized. These CPEs were characterized and their application in targeted hepatoma cell imaging was demonstrated.

Cellulose-based materials are well-suited for biomedical uses, because of their abundance, renewable nature, biodegradability, and relatively low cost. However, the set of commercially available cellulose esters and ethers is limited in number and diversity, and contains no cationically charged cellulose esters. Herein we report a simple, efficient strategy for synthesizing cationic, water-soluble co-polyelectrolytes from commercial, hydrophobic, renewable-based cellulose esters. Cellulose acetate (degree of substitution (DS) 1.78, CA320S), was the exemplary starting material for preparing these cationic polyelectrolytes by a reaction sequence of phosphine-catalyzed bromination and subsequent displacement by an aromatic amine, affording high reaction conversions. We show that these modification techniques can be carried out with essentially complete regio- and chemoselectivity, proceeding in the presence of multiple ester groups, yet preserving those groups. Availability of these novel polysaccharide-based electrolytes starting from uncharged, commercial, inexpensive cellulose esters may open up multiple new application areas, including in several aspects of gene or drug delivery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

To extend fossil oil supplies, sustainable feed stocks for the production of useful reagents and polymers should be harnessed. In this regard, chemicals derived from plants are excellent candidates. While the vast majority of plant sources used for polymer science only contain C x H y O z , alkaloids such as caffeine, nicotine, and theophylline possess nitrogen functionality that can provide new functions for bioderived polymers and their synthesis. In this context, the chemistry of theophylline, a natural product found in chocolate and tea, is exploited to create a cationic "poly(theophylline)" in a straightforward fashion for the first time. This work demonstrates how this new polymer can be synthesized and used for the creation of narrowly disperse cationic microspheres., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Spider dragline silk is a proteinaceous material that combines superior toughness and biocompatibility, which makes it a promising biomaterial. The distinct protein structure and the fiber formation process contribute to the superior toughness of dragline silk. Previously, we have produced recombinant spider silk-like proteins in transgenic tobacco that are readily purified from plant extracts. The plant-derived spidroin-like proteins consisted of native major ampullate spidroin 1 or spidroin 2 N- and C-termini flanking 8, 16, or 32 copies of their respective consensus block repeats (mini-spidroins). Here, we present the generation of fibers from mini-spidroins (rMaSp1R8 and rMaSp2R8) by polyelectrolyte complex formation using an anionic polyelectrolyte, gellan gum. Mini-spidroins, when treated with acetic acid and cross-linked by glutaraldehyde, formed a thin film at the interface when overlaid with a gellan gum solution. Immediate pulling of the film resulted in autofluorescent fibrous materials from either mini-spidroin alone or a combination of rMaSp1R8 and rMaSp2R8 (70:30). Addition of chitosan to the mini-spidroin solutions permitted continuous fiber production until the spinning dope supply was exhausted. When air-dried as-spun fibers were rehydrated and stretched in water, the fiber diameter decreased and the overall toughness improved. This study showed that spider silk-like fibers can be produced in large quantities through charge attraction that assembles chitosan, mini-spidroins, and gellan gum into fibrous complexes. We speculate that the spider silk self-assembly process in the duct may involve attraction of variously charged chitinous polymers, spidroins, and glycoproteins.

In this manuscript, a biscyclic monomer with an epoxide and a thiolactone ring connected by a urethane bond is used for the synthesis of amino acid-functional polyelectrolytes. In a first step, lithium salts of amino acids react selectively with the thiolactone ring by ring-opening, formation of an amide bond, and a thiol group. In a second step and in the presence of a base a polymeric building block is formed by polyaddition of the thiolate to the epoxide ring. The reaction occurs at room temperature in water as solvent. The resulting polymeric building block has a poly(thioether urethane) backbone, with hydroxyl- and amino acid side groups; the connection of the amino acid to the backbone occurs by an amide bond. As proof of concept, a selected series of amino acids and derivatives of such is used: glycine, alanine, tyrosine, glutamic acid, ε-amino caproic acid (as a lysine surrogate), BOC-lysine-O-methyl ester, BOC-lysine, and the dipeptide carnosine. The resulting polymer building blocks with molecular weights of M n = 1830-9590 g/mol are entirely based on both bio-based and biodegradable components. Exemplarily, using the lithium salts of glycine and lysine methyl ester, anionic and cationic polyelectrolyte building blocks are obtained. A mixture of the two polyelectrolyte solutions results in the formation of polyelectrolyte complexes (PECs). With decreasing concentration of the polyelectrolyte solutions, the radii of PECs decrease.

To enhance the glucose sensitivity and self-regulated release of insulin, biobased capsules with glucose-responsive and competitive properties were fabricated based on poly(γ-glutamic acid) (γ-PGA) and chitosan oligosaccharide (CS) polyelectrolytes. First, poly(γ-glutamic acid)-g-3-aminophenylboronic acid) (γ-PGA-g-APBA) and galactosylated chitosan oligosaccharide (GC) were synthesized by grafting APBA and lactobionic acid (LA) to γ-PGA and CS, respectively. The (γ-PGA-g-APBA/GC)5 capsules were then prepared by layer-by-layer (LBL) assembly of γ-PGA-g-APBA and GC via electrostatic interaction. The size and morphology of the particles and capsules were investigated by DLS, SEM, and TEM. The size of the (γ-PGA-g-APBA/GC)5 capsules increased with increasing glucose concentration due to the swelling of the capsules. The capsules could be dissociated at high glucose concentration due to the breaking of the cross-linking bonds between APBA and LA by the competitive reaction of APBA with glucose. The encapsulated insulin was able to undergo self-regulated release from the capsules depending on the glucose level and APBA composition. The amount of insulin release increased with incubation in higher glucose concentration and decreased with higher APBA composition. Moreover, the on-off regulation of insulin release from the (γ-PGA-g-APBA/GC)5 capsules could be triggered with a synchronizing and variation of the external glucose concentration, whereas the capsules without the LA functional groups did not show the on-off regulated release. Furthermore, the (γ-PGA-g-APBA/GC)5 capsules are biocompatible. These (γ-PGA-g-APBA/GC)5 with good stability, glucose response, and controlled insulin delivery are expected to be used for future applications to glucose-triggered insulin delivery.

Conjugated polyelectrolytes (CPEs) are macromolecules with highly delocalized π-conjugated backbones and charged side chains, which are unique types of active materials, with wide applications in optoelectronics, sensing, imaging, and therapy. By attaching specific groups (e.g., recognition elements, magnetic resonance (MR) contrast agents, gene carriers, and drugs) to the side chain or backbone of CPEs, functionalized CPEs have been developed and used for specific biological applications. In this account, we summarize the recent progress of functionalized CPEs with respect to their synthesis and biomedical applications. Future perspectives are also discussed at the end., (© 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polyelectrolyte multilayer (PEM) film formed due to the electrostatic interaction between oppositely charged polyelectrolytes is of considerable interest because of their potential applications as both drug carriers and surface-modifying agents. In this study, in vitro studies were carried out on polyelectrolyte complexes formulated with Eudragit E (EE) and hypromellose acetate succinate (HPMCAS). The complexes of EE and HPMCAS were formulated by non-stoichiometric method. The prepared IPCs were investigated using Fourier transform infrared spectroscopy. Diclofenac sodium (DS) tablets were prepared and were coated with polymer solution of HPMCAS and EE to achieve pH-dependent and sustained-release tablets. Tablets were evaluated for their physical characteristics and in vitro drug release. The results of pharmacokinetic studies in rabbits showed that the selected formulation (F6) exhibited a delayed peak plasma concentration and marked sustained-release effect of drug in the in vivo drug release in comparison with marketed tablet. The suitable combination of PEM film based on EE and HPMCAS demonstrated potential candidate for targeted release of DS in the lower part of the gastrointestinal (GI) tract.

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. Addition of Dopa enhanced the mass adsorption and led to the formation of a more compact structure. An increase of ionic strength induced an increase in mass adsorption in the Dopa-cross-linked multilayers. This is a universal approach for coating of various surfaces such as Au, SiO2, Ti, and Al2O3. Roughness observed by AFM in both wet and dry conditions was compared to confirm the compact morphology of Dopa-cross-linked multilayers. Because of the pH sensitivity of Dopa moiety, metal-chelated Dopa groups can be turned into softer structure at higher pH as revealed by reduction of Young's modulus determined by MFP-3D AFM. A deeper insight into the growth and mechanical properties of Dopa-cross-linked polyelectrolyte multilayers was addressed in the present study. This allows a better control of these systems for bioapplications.