Development of chitosan/sodium carboxymethyl cellulose-based polyelectrolyte complex of dexamethasone for treatment of anterior uveitis.

Anterior uveitis is one of the most prevalent forms of ocular inflammation caused by infections, trauma, and other idiopathic conditions if not treated properly, it can cause complete blindness. Therefore, this study aimed to formulate and evaluate dexamethasone sodium phosphate (DSP) loaded polyelectrolyte complex (PEC) nanoparticles (NPs) for the treatment of anterior uveitis. DSP-loaded PEC-NPs were formed through complex coacervation by mixing low molecular weight chitosan and the anionic polymer carboxy methyl cellulose. The formulations were optimized using Box-Behnken design and evaluated the effect of independent variables: Chitosan concentration, CMC concentration, and pH of chitosan solution on the dependent variables: particle (PS), Polydispersity Index (PDI), pH of the formulation, and % entrapment efficacy (%EE). The PS, PDI, ZP, and pH of the optimized formulation were found 451±82.0995nm, 0.3807±0.1862, +20.33±1.04mV and 6.8367±0.0737 respectively. The %EE and drug loading of formulation were 61.66±4.2914% and 21.442±1.814% respectively. In vitro drug release studies of optimized formulation showed the prolonged release up to 12 hours whereas, the marketed formulation showed the burst release 85.625 ± 4.3062% in 1 hour and 98.1462± 3.0921% at 6 h, respectively. FTIR studies suggested the effective incorporation of the drug into the PEC-NPs formulation whereas DSC and XRD studies showed the amorphized nature of the drug in the formulation. TEM study showed self-assembled, nearly spherical, core-shell nanostructures. The corneal permeation study showed higher permeation of the drug from PEC-NPs compared to the marketed formulation. HET-CAM test of the optimized formulation revealed non-irritant and safe for ocular administration. Therefore, DSP-loaded PEC-NPs are an effective substitute for conventional eye drops due to their ability to increase bioavailability through longer precorneal retention duration and sustained drug release. .

Lactoferrin-Based Heteroprotein Systems, From Their Formation Mechanism, Properties, To Applications.

Lactoferrin (LF) is an important iron-binding glycoprotein found in milk and mucosal secretions. The alkaline lactoferrin can interact with some acidic proteins to form heteroprotein systems with multifunctional properties and a wide range of applications. Lactoferrin can interact with animal and plant proteins mainly through the electrostatic forces, dipolar attraction, and hydrophobic interactions. In this review, the types of heteroprotein complexes formed by the complex coacervation of lactoferrin with other proteins are introduced, including the preparation, structure, and applications. The factors affecting the formation of heteroprotein complexes are described, such as pH, ionic strength, mixing ratio, total protein concentration, and temperature. The issues and challenges in the formation of heteroprotein complexes are also discussed.

Pea protein - gum Arabic gel addition as ingredient to increase protein, fiber and decrease lipid content in muffins without impair the texture and intestinal microbiota.

This study evaluated the use of a protein-polysaccharide gel (PGEL) as a muffin ingredient, and its effect on the nutritional, textural, and gut microbiome profiles. PGEL was generated by complex coacervation with Pea protein and Gum Arabic. A mixture design was performed with different flour, lipids, and PGEL proportions, where Tx9 (26 % PGEL) showed improved physicochemical characteristics. Optimization was performed using 3 variables, hardness, protein content, and in vitro protein digestibility, to generate an optimal muffin with PGEL (PGEL-Muffin). PGEL-Muffin had a positive effect in its nutritional content and texture (protein: 12.03 %, fiber: 7.90 %, lipids: 9.23 %, and hardness: 4.41 N) compared to a muffin without protein addition (Control) and a muffin with added pea protein powder (Powder-Muffin). PGEL-Muffin did not modify gut microbiome using an ex-vivo system after 4-days of administration. PGEL ingredient could be an opportunity to develop nutritionally improved products without a negative impact on textural properties.

Coacervation-Driven Semipermeable Nanoreactors for Enzymatic Cascade-Mediated Cancer Combination Therapy with Enhanced Efficacy.

Utilizing enzyme cascades as a promising approach for targeted cancer therapies holds significant potential, yet its clinical effectiveness is substantially hindered by functional losses during delivery. Complex coacervation emerges as an intriguing strategy for designing functional nanoreactors. In this study, a noteworthy achievement is presented in the development of lactobionic acid-modified tumor microenvironment (TME)-responsive polyelectrolyte complex vesicles (HGS-PCVs) based on bioinspired homopolypeptoids, which serve as a facile, intelligent, and highly efficient nanoreactor tunable for glucose oxidase, hemoglobin, and sorafenib (SRF) to hepatic cancer cells. The TME-responsive permeability of HGS-PCVs enables the selective entry of glucose into their interior, triggering an enzymatic cascade reaction within the tumor. This intricate process generates toxic hydroxyl radicals while concurrently lowering the pH. Consequently, this pH shift enhances the SRF release, effectively promoting ferroptosis and apoptosis in the target cancer cells. Further, the administration of the HGS-PCVs not only initiates immunogenic cell death but also plays a crucial role in inducing the maturation of dendritic cells within lymph nodes. It stimulates an adaptive T-cell response, a crucial mechanism that contributes to impeding the growth of distant tumors in vivo, demonstrating the promising potential of PCVs for cancer immunotherapy.

Emerging encapsulation strategies for vitamin A fortification in food sector: an overview.

Micro- and nano-encapsulation techniques, such as microfluidization, spray drying, and centrifugal extrusion, have been widely utilized in various industries, including pharmaceuticals, food, cosmetics, and agriculture, to improve the stability, shelf life, and bioavailability of active ingredients, such as vitamin A. Emulsion-based delivery platforms offer feasible and appropriate alternatives for safeguarding, encapsulating, and transporting bioactive compounds. Therefore, there is a need to enrich our basic diet to prevent vitamin A deficiency within a population. This review focused on addressing vitamin A shortages, encapsulation techniques for improving the delivery of vital vitamins A and their food applications. Additionally, more studies are required to guarantee the security of nano-delivery strategies, as they proliferate in the food and beverage sector.

Coenzyme Q10-loaded microcapsules stabilized by glyceryl monostearate and soy protein isolates-flaxseed gum: Characterization, in vitro release and digestive behavior.

This study aimed to stabilize microcapsules with core materials of glyceryl monostearate (GMS) and octyl and decyl glycerate, and wall materials of soy protein isolates (SPI) and flaxseed gum (FG) by complex coacervation method to overcome the drawbacks of coenzyme Q10 (CoQ10). It was demonstrated by the study that the obtained microcapsules were irregular aggregates. Differential scanning calorimetry and x-ray diffraction patterns indicated that CoQ10 was entrapped inside the disordered semisolid cores of microcapsules. The CoQ10 loading and encapsulation efficiency analysis revealed that GMS and FG helped CoQ10 better encapsulated inside the microcapsules. The in vitro release curve showed a "burst" release of CoQ10 absorbed on the surface of microcapsules for the first 180 min, followed by a sustained release of the encapsulated CoQ10. GMS and FG contributed to the sustained release and the release mechanism of the microcapsules was Fickian diffusion. The in vitro simulated digestion demonstrated that the constructed microcapsules improved the bio-accessibility of CoQ10. Finally, due to the protection of GMS and FG, microcapsules had good storage stability. In conclusion, this study emphasized the potential of using new microcapsules to deliver and protect lipophilic ingredients, providing valuable information for developing functional foods with higher bioavailability.

Complexation of Olive Protein with Soluble Dietary Fibers: A Way to Improve the Functional Properties of Proteins and Efficiently Utilize Olives.

High-value resources beyond oil extraction for the olive industry need to be developed due to increased olive production. Soluble dietary fibers (SDFs) and olive proteins (OPIs) are important components of olives. However, the commercial production process partially damages OPIs' emulsifying and foaming properties. Thus, the preparation of SDF-OPI complexes would help protect and even improve the emulsifying and foaming properties. The effects of pH and thermal-ultrasonic treatment on the complexation were explored, which showed that the SDF-OPI complexes prepared at pH 5 exhibited superior solubility (p < 0.05). SDF addition noticeably improved OPI thermal stability, emulsifying properties, and foaming properties. Moreover, the complexes prepared by thermal-ultrasonic treatment exhibited higher emulsion stability and lower emulsification activity than those prepared without thermal-ultrasonic treatment. In the acidic system, the electrostatic interaction was considered the main driving factor, assisted by the hydrophobic interaction. Additionally, after thermal-ultrasonic treatment, the covalent binding was observed by infrared spectroscopy. These results revealed the interaction mechanism between SDF and OPI, and the complexes significantly enhanced the functional properties of OPI. This study provides a reference for the high-value utilization of olives, thus broadening their potential uses in the food sector and beyond.

A DNA condensation code for linker histones.

Linker histones play an essential role in chromatin packaging by facilitating compaction of the 11-nm fiber of nucleosomal "beads on a string." The result is a heterogeneous condensed state with local properties that range from dynamic, irregular, and liquid-like to stable and regular structures (the 30-nm fiber), which in turn impact chromatin-dependent activities at a fundamental level. The properties of the condensed state depend on the type of linker histone, particularly on the highly disordered C-terminal tail, which is the most variable region of the protein, both between species, and within the various subtypes and cell-type specific variants of a given organism. We have developed an in vitro model system comprising linker histone tail and linker DNA, which although very minimal, displays surprisingly complex behavior, and is sufficient to model the known states of linker histone-condensed chromatin: disordered "fuzzy" complexes ("open" chromatin), dense liquid-like assemblies (dynamic condensates), and higher-order structures (organized 30-nm fibers). A crucial advantage of such a simple model is that it allows the study of the various condensed states by NMR, circular dichroism, and scattering methods. Moreover, it allows capture of the thermodynamics underpinning the transitions between states through calorimetry. We have leveraged this to rationalize the distinct condensing properties of linker histone subtypes and variants across species that are encoded by the amino acid content of their C-terminal tails. Three properties emerge as key to defining the condensed state: charge density, lysine/arginine ratio, and proline-free regions, and we evaluate each separately using a strategic mutagenesis approach.

Two Methods Based on Integral Equation Approaches in Analyzing Polyelectrolyte Solutions: Macrophase Separation.

To understand the phase behaviors of polyelectrolyte solutions, we provide two analytical methods to formulate a molecular equation of state for a system of fully charged polyanions (PAs) and polycations (PCs) in a monomeric neutral component, based on integral equation theories. The mixture is treated in a primitive and restricted manner. The first method utilizes Blum's approach to charged hard spheres, incorporating the chain connectivity contribution by charged spheres via Stell's cavity function method. The second method employs Wertheim's multi-density Ornstein-Zernike treatment of charged hard spheres with Baxter's adhesive potential. The pressures derived from these methods are compared to available molecular dynamics simulations data for a solution of PAs and monomeric counterions as a limiting case. Two-phase equilibrium for the system is calculated using both methods to evaluate the relative strength of phase segregation that leads to complex coacervation. Additionally, the scaling exponents for a selected solution near its critical point are examined.

Encapsulation of ß-carotene in gelatin-gum Arabic-sodium carboxymethylcellulose complex coacervates: Enhancing surimi gel properties and exploring 3D printing potential.

This study investigates the utilization of functional additives (ß-carotene microcapsules) and 3D printing technology for the production of innovative surimi products. The ß-carotene microcapsules were prepared using different ratios of gelatin (Ge), gum Arabic (Ara), and carboxymethylcellulose sodium (CMC). Among these ratios, the ratio of 5:5:1 (Ge:Ara:CMC) resulted in more stable microcapsules spherical structures and better environmental stability. Subsequently, different concentrations (5-20 %) of the obtained ß-carotene microcapsules were added to surimi samples. As the concentration increased, there was an improvement in the gel strength of the surimi. However, no significant changes were observed when the concentration was 15 % (p > 0.05). All samples exhibited shear thinning behavior. The addition of microcapsules improved the resilience and thixotropy of surimi, making it more suitable for 3D printing applications. The inclusion of ß-carotene microcapsules in surimi products not only meets the nutritional needs of consumers, but also provides valuable insights for the development of functional surimi products.

Embedding Bioprinting of Low Viscous, Photopolymerizable Blood-Based Bioinks in a Crystal Self-Healing Transparent Supporting Bath.

Protein-based hydrogels have great potential to be used as bioinks for biofabrication-driven tissue regeneration strategies due to their innate bioactivity. Nevertheless, their use as bioinks in conventional 3D bioprinting is impaired due to their intrinsic low viscosity. Using embedding bioprinting, a liquid bioink is printed within a support that physically holds the patterned filament. Inspired by the recognized microencapsulation technique complex coacervation, crystal self-healing embedding bioprinting (CLADDING) is introduced based on a highly transparent crystal supporting bath. The suitability of distinct classes of gelatins is evaluated (i.e., molecular weight distribution, isoelectric point, and ionic content), as well as the formation of gelatin-gum arabic microparticles as a function of pH, temperature, solvent, and mass ratios. Characterizing and controlling this parametric window resulted in high yields of support bath with ideal self-healing properties for interaction with protein-based bioinks. This support bath achieved transparency, which boosted light permeation within the bath. Bioprinted constructs fully composed of platelet lysates encapsulating a co-culture of human mesenchymal stromal cells and endothelial cells are obtained, demonstrating a high-dense cellular network with excellent cell viability and stability over a month. CLADDING broadens the spectrum of photocrosslinkable materials with extremely low viscosity that can now be bioprinted with sensitive cells without any additional support.

Reflectivity and Angular Anisotropy of Liquid Crystal Microcapsules with Different Particle Sizes by Complex Coalescence.

Cholesteric liquid crystal microcapsules (CLCMs) are used to improve the stability of liquid crystals while ensuring their stimulus response performance and versatility, with representative applications such as sensing, anticounterfeiting, and smart fabrics. However, the reflectivity and angular anisotropy decrease because of the anchoring effect of the polymer shell matrix, and the influence of particle size on this has not been thoroughly studied. In this study, the effect of synthesis technology on microcapsule particle size was investigated using a complex coalescence method, and the effect of particle size on the reflectivity and angular anisotropy of CLCMs was investigated in detail. A particle size of approximately 66 µm with polyvinyl alcohol (PVA, 1:1) exhibited a relative reflectivity of 16.6% and a bandwidth of 20 nm, as well as a narrow particle size distribution of 22 µm. The thermosetting of microcapsules coated with PVA was adjusted and systematically investigated by controlling the mass ratio. The optimized mass ratio of microcapsules (66 µm) to PVA was 2:1, increasing the relative reflectivity from 16.6% (1:1) to 32.0% (2:1) because of both the higher CLCM content and the matching between the birefringence of the gelatin-arabic shell system and PVA. Furthermore, color based on Bragg reflections was observed in the CLCM-coated ortho-axis and blue-shifted off-axis, and this change was correlated with the CLCM particle size. Such materials are promising for anticounterfeiting and color-based applications with bright colors and angular anisotropy in reflection.

Fuel-Driven Dynamic Combinatorial Peptide Libraries.

Dynamic combinatorial chemistry (DCC) creates libraries of molecules that are constantly interchanging in a dynamic combinatorial library. When a library member self-assembles, it can displace the equilibria, leading to emergent phenomena like its selection or even its replication. However, such dynamic combinatorial libraries typically operate in or close to equilibrium. This work introduces a new dynamic combinatorial chemistry fueled by a catalytic reaction cycle that forms transient, out-of-equilibrium peptide-based macrocycles. The products in this library exist out of equilibrium at the expense of fuel and are thus regulated by kinetics and thermodynamics. By creating a chemically fueled dynamic combinatorial library with the vast structural space of amino acids, we explored the liquid-liquid phase separation behavior of the library members. The study advances DCCs by showing that peptide structures can be engineered to control the dynamic library's behavior. The work paves the way for creating novel, tunable material systems that exhibit emergent behavior reminiscent of biological systems. These findings have implications for the development of new materials and for understanding life's chemistry.

Understanding emulsifier influence on complex coacervation: Essential oils encapsulation perspective.

The objective of this research was to explore the viability of pea protein as a substitute for gelatin in the complex coacervation process, with a specific focus on understanding the impact of incorporating an emulsifier into this process. The study involved the preparation of samples with varying polymer mixing ratios (1:1, 1:2, and 2:1) and emulsifier content. As core substances, black pepper and juniper essential oils were utilized, dissolved beforehand in grape seed oil or soybean oil, to minimize the loss of volatile compounds. In total, 24 distinct samples were created, subjected to freeze-drying to produce powder, and then assessed for their physicochemical properties. Results revealed the significant impact of emulsifier addition on microcapsule parameters. Powders lacking emulsifiers exhibited higher water solubility (57.10%-81.41%) compared to those with emulsifiers (24.64%-40.13%). Moreover, the emulsifier significantly decreased thermal stability (e.g., without emulsifier, Ton = 137.21°C; with emulsifier, Ton = 41.55°C) and adversely impacted encapsulation efficiency (highest efficiency achieved: 67%; with emulsifier: 21%).

Persistence of the Antibacterial and Antiviral Effects after Skin Cleansing ~A New Approach to Suppress the Contact Infection~.

Handwashing represents an important personal hygiene measure for preventing infection. Herein, we report the persistence of antibacterial and antiviral effects after handwashing with fatty acid salt-based hand soap. To this end, we developed a new in vitro test method to measure persistence, utilizing coacervation formed by anionic surfactants and cationic polymers to retain highly effective soap components against each bacterium and virus on the skin. Coacervation with fatty acid salts and poly diallyldimethylammonium chloride (PDADMAC) as a cationic polymer allowed the persistence of antibacterial and antiviral effects against E. coli, S. aureus, and influenza virus even 4 h after handwashing. Furthermore, we confirmed an increase in the number of residual components effective against each bacterium and virus on the skin. In summary, the current findings describe an effective approach for enhancing the protective effects of handwashing.

Carbomer Hydrogels with Microencapsulated α-Tocopherol: Focus on the Biocompatibility of the Microcapsules, Topical Application Attributes, and In Vitro Release Study.

The microencapsulation of α-tocopherol based on the complex coacervation of low-molecular-weight chitosan (LMWC) and sodium lauryl ether sulphate (SLES) without harmful crosslinkers can provide biocompatible carriers that protect it from photodegradation and air oxidation. In this study, the influence of the microcapsule wall composition on carrier performance, compatibility with a high-water-content vehicle for topical application, and release of α-tocopherol were investigated. Although the absence of aldehyde crosslinkers decreased the encapsulation efficiency of α-tocopherol (~70%), the variation in the LMWC/SLES mass ratio (2:1 or 1:1) had no significant effect on the moisture content and microcapsule size. The prepared microcapsule-loaded carbomer hydrogels were soft semisolids with pseudoplastic flow behavior. The integrity of microcapsules embedded in the hydrogel was confirmed by light microscopy. The microcapsules reduced the pH, apparent viscosity, and hysteresis area of the hydrogels, while increasing their spreading ability on a flat inert surface and dispersion rate in artificial sweat. The in vitro release of α-tocopherol from crosslinker-free microcapsule-loaded hydrogels was diffusion-controlled. The release profile was influenced by the LMWC/SLES mass ratio, apparent viscosity, type of synthetic membrane, and acceptor medium composition. Better data quality for the model-independent analysis was achieved when a cellulose nitrate membrane and ethyl alcohol 60% w/w as acceptor medium were used.

Recovery of rare earth elements from low-grade coal fly ash using a recyclable protein biosorbent.

Rare earth elements (REEs), including those in the lanthanide series, are crucial components essential for clean energy transitions, but they originate from geographically limited regions. Exploiting new and diverse supply sources is vital to facilitating a clean energy future. Hence, we explored the recovery of REEs from coal fly ash (FA), a complex, low-grade industrial feedstock that is currently underutilized (leachate concentrations of REEs in FA are < 0.003 mol%). Herein, we demonstrated the thermo-responsive genetically encoded REE-selective elastin-like polypeptides (RELPs) as a recyclable bioengineered protein adsorbent for the selective retrieval of REEs from coal fly ash over multiple cycles. The results showed that RELPs could be efficiently separated using temperature cycling and reused with high stability, as they retained ∼95% of their initial REE binding capacity even after four cycles. Moreover, RELPs selectively recovered high-purity REEs from the simulated solution containing one representative REE in the range of 0.0001-0.005 mol%, resulting in up to a 100,000-fold increase in REE purity. This study offers a sustainable approach to diversifying REE supplies by recovering REEs from low-grade coal fly ash in industrial wastes and provides a scientific basis for the extraction of high-purity REEs for industrial purposes.

Microencapsulation of Essential Oils Using Faba Bean Protein and Chia Seed Polysaccharides via Complex Coacervation Method.

The aim of this study was to develop microcapsules containing juniper or black pepper essential oils, using a combination of faba bean protein and chia seed polysaccharides (in ratios of 1:1, 1:2, 2:1). By synergizing these two polymers, our goal was to enhance the efficiency of essential oil microencapsulation, opening up various applications in the food industry. Additionally, we aimed to investigate the influence of different polymer mixing ratios on the properties of the resulting microcapsules and the course of the complex coacervation process. To dissolve the essential oils and limit their evaporation, soybean and rapeseed oils were used. The powders resulting from the freeze-drying of coacervates underwent testing to assess microencapsulation efficiency (65.64-87.85%), density, flowability, water content, solubility, and hygroscopicity. Additionally, FT-IR and DSC analyses were conducted. FT-IR analysis confirmed the interactions between the components of the microcapsules, and these interactions were reflected in their high thermal resistance, especially at a protein-to-polysaccharide ratio of 2:1 (177.2 °C). The water content in the obtained powders was low (3.72-7.65%), but it contributed to their hygroscopicity (40.40-76.98%).

Superstrong Ionogel Enabled by Coacervation-Induced Nanofibril Assembly for Sustainable Moisture Energy Harvesting.

Ionogels have grabbed significant interest in various applications, from sensors and actuators to wearable electronics and energy storage devices. However, current ionogels suffer from low strength and poor ionic conductivity, limiting their performance in practical applications. Here, inspired by the mechanical reinforcement of natural biomacromolecules through noncovalent aggregates, a strategy is proposed to construct nanofibril-based ionogels through complex coacervation-induced assembly. Cellulose nanofibrils (CNFs) can bundle together with poly(ionic liquid) (PIL) to form a superstrong nanofibrous network, in which the ionic liquid (IL) can be retained to form ionogels with high liquid inclusion and ionic conductivity. The strength of the CNF-PIL-IL ionogels can be tuned by the IL content over a wide range of up to 78 MPa. The optical transparency, high strength, and hygroscopicity enabled them to be promising candidates in moist-electricity generation and applications such as energy harvesting windows and wearable power generators. In addition, the ionogels are degradable and the ionogel-based generators can be recycled through dehydration. Our strategy suggests perspectives for the fabrication of high-strength and multifunctional ionogels for sustainable applications.

Microencapsulation of flaxseed oil in pea protein-gum arabic complex coacervates delays lipid digestion in liquid yoghurt.

Flaxseed oil coacervates were produced by complex coacervation using soluble pea protein and gum arabic as shell materials, followed by either spray or electrostatic spray drying and their incorporation to yoghurt. Three yoghurt formulations were prepared: yoghurt with spray-dried microcapsules (Y-SD); with electrospray-dried microcapsules (Y-ES); with the encapsulation ingredients added in free form (Y). The standardised semi-dynamicin vitrodigestion method (INFOGEST) was employed to study the food digestion. The structure was analysed by confocal laser scanning microscopy and particle size distribution. Protein and lipid digestion were monitored by cumulated protein/free NH2 release and cumulated free fatty acids release, respectively. Stable microcapsules were observed during gastric digestion, but there was no significant difference in protein release/hydrolysis among samples until 55 min of gastric digestion. Formulation Y showed less protein release after 74 min (40.46 %) due to the free SPP being available and positively charged at pH 2-4, resulting in interactions with other constituents of the yoghurt, which delayed its release/hydrolysis. The total release of protein and free NH2 by the end of intestinal digestions ranged between 46.56-61.15 % and 0.83-1.57 µmol/g protein, respectively. A higher release of free fatty acids from formulation Y occurred at the end of intestinal digestion, implying that coacervates promoted the delayed release of encapsulated oil. In summary, incorporating protein-polysaccharides-based coacervates in yoghurt enabled the delay of the digestion of encapsulated lipids but accelerated the digestion of protein, suggesting a promising approach for various food applications.