Thermoreversible Gels Research Articles

Ethyl Cellulose-Based Thermoreversible Organogel Photoresist for Sedimentation-Free Volumetric Additive Manufacturing.

Liquid photoresists are abundant in the field of light-based additive manufacturing (AM). However, printing unsupported directly into a vat of material in emerging volumetric AM technologies-typically a benefit due to fewer geometric constraints and less material waste-can be a limitation when printing low-viscosity liquid monomers and multimaterial constructs due to part drift or sedimentation. With ethyl cellulose (EC), a thermoplastic soluble in organic liquids, a simple three-component transparent thermoreversible gel photoresist with melting temperature of ≈64 °C is formulated. The physically crosslinked network of the gel leads to storage moduli in the range of 0.1-10kPa and maximum yield stress of 2.7kPa for a 10 wt% EC gel photoresist. Nonzero yield stress enables sedimentation-free tomographic volumetric patterning in low-viscosity monomer without additional hardware or modification of apparatus. In addition, objects inserted into the print container can be suspended in the gel material which enables overprinting of multimaterial devices without anchors connecting the object to the printing container. Flexural strength is also improved by 100% compared to the neat monomer for a formulation with 7 wt% EC.

Thermoreversible Gels of Poly(l-lactide)/Poly(d-lactide) Blends: A Facile Route to Prepare Blend α-Form and Stereocomplex Aerogels

The demand for biodegradable polymer-based aerogels with superior comprehensive properties has escalated in various fields of application, such as packaging, tissue engineering, thermal insulation, acoustic insulation, and environmental remediation. In this work, we report a facile strategy for enhancing the thermal and mechanical properties of polylactide (PLA) aerogels through the stereocomplex (SC) formation between the opposite enantiomers. Thermoreversible gelation of poly(l-lactide) (PLLA)/poly(d-lactide) (PDLA) blend in crystal complex forming solvent and the subsequent thermal annealing of the gel resulted in crystalline pure SC gel, which, upon solvent exchange with water and freeze-drying, furnished robust SC aerogel. It was found that the SC content could be tuned by varying the annealing temperature of the blend gel and that we could prepare blend aerogels with pure α crystalline form and a mixture of α and SC. Crystalline pure blend α aerogel showed fibrillar morphology, whereas SC aerogel exhibited unique interwoven ball-like microstructures interconnected by PLLA and PDLA chains. The structural evolution during SC formation at the molecular level and the micrometer length scale instigated better properties in the PLA aerogels. When compared with the homopolymer aerogels, the crystalline pure SC aerogel showed an enhanced melting temperature of 227 ± 2 °C (50 °C higher), better thermal stability (onset of degradation was delayed by ∼40 °C), enhanced mechanical strength (compression modulus of 3.3 MPa), and better sound absorption ability. The biodegradability of PLA and the superior properties induced by stereocomplexation make these aerogels potential candidates for applications such as tissue engineering scaffolds, packaging, acoustic insulation, etc.

Thermoproteus uzoniensis 4-α-glucanotransferase catalyzed production of a thermo-reversible potato starch gel with superior rheological properties and freeze-thaw stability

Solid-liquid thermo-reversibility, lacking in raw starch is an important property for gels allowing repeated thermal processing in food. In this work, the Thermoproteus uzoniensis 4-α-glucanotransferase (TuαGT) was used to modify five different starches from potato, corn, rice, wheat, and pea and the thermo-reversibility of the modified starch gels was evaluated by rheological assay. Only modified potato starch (MPS) exhibited thermo-reversibility, which prompted us to perform detailed analyses of the structural and gel properties of this product. The enzymatic modification resulted in a marked decrease in amylopectin side chains with a degree of polymerization (DP) < 23, while the contents of side chains with DP 23–43 increased. These data indicated that TuαGT preferentially extended the outer chains of amylopectin using amylose as a donor, which resulted in 17% increase in the amylopectin molecular weight to 3.0 × 10 7 g/mol. Notably, MPS displayed a delayed retrogradation and improved stability in four freeze-thaw cycles (−70 °C and 25 °C) as compared to the native starch. These analyses supported a model to explain the TuαGT catalyzed conversion of potato starch to a thermo-reversible product. Importantly, the MPS thermo-reversible 6% (w/v) gel showed comparable rheological properties to a 1.5% (w/v) κ-carrageenan hydrocolloid, highlighting the potential of MPS as a substitute to κ-carrageenan and other hydrocolloids of emerging health concerns. This work offers a starch based thermo-reversible gel and a methodological framework to broadens the use of starch into novel application as a food ingredient. • Thermo-reversible gel was prepared from potato starch by modification with TuαGT. • TuαGT had a preference for outer shorter chains in amylopectin. • Thermo-reversible potato starch gel had excellent resistance to retrogradation. • Thermo-reversible potato starch gel had good freeze-thaw stability. • Modified potato starch gel of 6% had the potential to substitute for 1.5% κ-carrageenan.

Thermo-reversible gelation of myofibrillar protein: Relationship between coiled-coil and thermal reversibility

Thermo-reversible gel of myofibrillar protein (MP) can be made by tactics of elaborate deamidation using protein-glutaminase (PG), and this work aimed to disclose the link between thermally reversible gelation of MP and the coiled-coil (CC). Enzymatic deamidation fragmented myofibril filaments and triggered structural reassembly to create small-sized aggregates. The coiling and dissociation of CC structure in the myosin tails is the fundamental structural basis of the PG deamidated MP (DMP) in the dynamic evolution of reversible gelation. After specific inhibition of CC assembly by trifluoroethanol (TFE), the thermo-reversible gel ability of DMP was impaired, which confirmed that the dynamic assembly of CC with temperature response played a key role in the thermo-reversible gelation of DMP. The findings may broaden the molecular basis of natural CC reversible gelation and foster advances for the development of new muscle protein products.

Frictional properties of phase-separated agarose hydrogels in water permeation.

We studied the friction coefficient between the polymer gel network and water f for thermoreversible agarose gels under various conditions of agarose concentration and gelation temperature. Since agarose gels exhibit phase separation below the gelation temperature, f strongly depends on the thermal history. We found that the friction coefficient of the phase-separated agarose gel normalized by the water viscosity, f/η, is expressed as f/η = S/ξνSD where ξSD is the frictional pore size and ν and S are constant parameters. ξSD corresponds to the correlation length of the frozen density fluctuations of the polymers via spinodal decomposition determined from small-angle light scattering. The least-squares analysis of the results shows that the exponent is ν ≃ 2 with the numerical constant of S ≃ 105/2π. The results suggest that the frictional properties of phase-separated agarose gels are dominated by the dilute regions of the bicontinuous gel structure.

A monocarboxylic acid induction strategy to prepare tough and thermo-reversible poly(vinyl alcohol) physical gels with high transparency.

To date, poly(vinyl alcohol) (PVA) gels attract tremendous attention because of their potential applications in a wide variety of fields. Here, a novel monocarboxylic acid induction strategy was developed to fabricate tough and thermo-reversible PVA physical gels by introducing monocarboxylic acids into the PVA/dimethyl sulfoxide (DMSO) system. The obtained PVA gels exhibited appropriate crystalline architectures, leading to superior mechanical properties and high transparency. Furthermore, the role of monocarboxylic acids in the formation of PVA physical gels and the effects of alkyl chain length, concentration, and the induction time of monocarboxylic acids on the properties of PVA physical gels were also investigated.

Effect of isopropyl alcohol and poloxamer 407 on gelation temperature and critical quality attributes of thermo-reversible gel formulation

Effect of isopropyl alcohol and poloxamer 407 on gelation temperature and critical quality attributes of thermo-reversible gel formulation

QIZILABALIĞIN KALSİTONİNİNDƏN ALINMIŞ TERMOREVERSİV GELİN VƏ SPREY FORMASININ İNTRANAZAL MÜQAYİSƏSİ

In the current study, we developed original thermoreversible nasal gel (solgel) formulations of salmon calci-tonin (sCT). The effects of solgel have been confront with histologically with the original intranasal spray in sep-tums of rabbits. Solgel form has ability for a reversible adequate fluidity in the temperature of nasal area in pH 3 and 4. The residence time of the solution, which turns into a gel form, may be longer. Analytical assay was validated to determine the amount of sCT. Histopathological findings of the mucous membranes from rabbit septums were examined by light microscope. Inflammatory cell infiltration in the lamina propria, increase in Goblet cells, decrease in cilia loss and epithelial layer thickness were enumerated. The statistical evaluation were calculated by Krusskal-Wallis test. In the electron microsco py tissue samples were examined and developed formulations were found better than commercial spray histologically. Solgels are formulated to become gels according to the temperature of nasal mucosa (32-34 °C). Content uniformity of each application dose was provided as 450 µg sCT in sprays. Nasal mucosa grading of the groups was evaluated and statistically the dif-ferences were significant (p&lt;0.05). In each deformation group commercial spray had significant changes than our formulations. Also in electron microscop examination, commercial spray group had intense separation of respiratory epithelial cells and ciliary loss however developed formulations were normal. Solgel formulations were comfortable and easy to use. they may be a good alternative for intranasal administrations. Developed solgels were evaluated less harmful to nasal mucosa histologically.

Integration of flexible, recyclable, and transient gelatin hydrogels toward multifunctional electronics

Facing the challenges posed by exponentially increasing e-waste, the development of recyclable and transient electronics has paved the way to an environmentally-friendly progression strategy, where electronics can disintegrate and/or degrade into eco-friendly end products in a controlled way. Natural polymers possess cost and energy efficiency, easy modification, and fast degradation, all of which are ideal properties for transient electronics. Gelatin is especially attractive due to its unique thermoreversible gelation processes, yet its huge potential as a multifunctional electronic material has not been well-researched due to its limited mechanical strength and low conductivity. Herein, we explored versatile applications of gelatin-based hydrogels through the assistance of multifunctional additives like carbon nanotubes to enhance their electromechanical performances. The optimized gelatin hydrogel displays not only a high conductivity of 0.93 S/m, electromagnetic shielding effectiveness of 39.6 dB, and tensile stress tolerance of 263 kPa, but also shows a negative permittivity phenomenon, which may find versatile applications in novel electronics. As a proof of concept, hydrogels were assembled as wearable sensors to sensitively detect static and dynamic pressures and strains generated by solids, liquids, and airflow, as well as diverse body movements. Furthermore, the recyclability, biocompatibility, and degradability of gelatin-based hydrogels were well studied and analyzed. This work outlines a facile method to design multifunctional transient materials for wearable, sustainable, and eco-friendly electronics.

Enabling Solution Processable COFs through Suppression of Precipitation during Solvothermal Synthesis.

Covalent organic frameworks (COFs) are crystalline, nanoporous materials of interest for various applications, but current COF synthetic routes lead to insoluble aggregates which precludes processing for practical implementation. Here, we report a COF synthesis method that produces a stable, homogeneous suspension of crystalline COF nanoparticles that enables the preparation of COF monoliths, membranes, and films using conventional solution-processing techniques. Our approach involves the use of a polar solvent, diacid catalyst, and slow reagent mixing procedure at elevated temperatures which altogether enable access to crystalline COF nanoparticle suspension that does not aggregate or precipitate when kept at elevated temperatures. On cooling, the suspension undergoes a thermoreversible gelation transition to produce crystalline and highly porous COF materials. We further show that the modified synthesis approach is compatible with various COF chemistries, including both large- and small-pore imine COFs, hydrazone-linked COFs, and COFs with rhombic and hexagonal topologies, and in each case, we demonstrate that the final product has excellent crystallinity and porosity. The final materials contain both micro- and macropores, and the total porosity can be tuned through variation of sample annealing. Dynamic light scattering measurements reveal the presence of COF nanoparticles that grow with time at room temperature, transitioning from a homogeneous suspension to a gel. Finally, we prepare imine COF membranes and measure their rejection of polyethylene glycol (PEG) polymers and oligomers, and these measurements exhibit size-dependent rejection and adsorption of PEG solutes. This work demonstrates a versatile processing strategy to create crystalline and porous COF materials using solution-processing techniques and will greatly advance the development of COFs for various applications.

Myofibrillar protein can form a thermo-reversible gel through elaborate deamidation using protein-glutaminase.

Novel thermo-reversible hydrogels that undergo gelation in feedback to external stimuli have numerous applications in the food, biomedical, and functional materials fields. Muscle myofibrillar protein (MP) has long been known for thermally irreversible gelation. Once the reversible gelation of MP is achieved, its scope for research and application will expand. The work reported here achieved, for the first time, a thermo-reversible MP gelation by elaborate deamidation using protein glutaminase (PG). The protein concentration and PG reaction time within windows of 1.0-2.5% and 8h or 12 h were observed to be vital for creating thermo-reversible gels. The gel strength increased with protein concentration. The gel displayed a perforated lamellar microstructure, which resulted in a high water-holding capacity. The rheological results revealed the thermo-reversibility of the gel was robust for up to five cycles of heating and cooling. The thermally reversible gelation is closely related to the reversible assembly between individual α-helix and helical coiled coil. Hydrophobic interactions proved to be predominantly involved in the formation and stabilization of the gel network structure. This work increases the scope of research into the thermo-responsive behavior of MP-based gel. It can foster advances in research into the applications of muscle proteins and into the use of PG as a novel ingredient in the food industry. © 2022 Society of Chemical Industry.

Development and optimization of candesartan cilexetil nasal gel for accentuated intranasal delivery using central composite design

The investigation was intended to create a mucoadhesive thermoreversible gel containing candesartan cilexetil for enhanced nasal drug delivery using a quality by design approach. Thermoreversible gel formulation bearing candesartan cilexitil was developed by cold method. The central composite design was used for the candesartan-loaded nasal gel optimization. The Pluronic® F-127 (poloxamer 407), carbopol 934P, and polyethylene glycol were used as independent variables while gelation temperature and drug content were taken as the dependent variables. The formulation optimized by design was further evaluated for pH, permeation study, and mucoadhesive strength. The optimized thermoreversible nasal gel formulation shows a gelation temperature of 27 ± 1 °C and drug content of 99.13 ± 0.55 %. The viscosity and pH of the optimized formulation were found to be 23.25 ± 0.36 Pa.S and 6.4 ± 0.1 respectively. Conclusion: The developed nasal gel formulation shows the enhanced delivery of candesartan cilexitil due to the presence of the permeation enhancer in comparison to the drug solution. The improved mucoadhesive strength, and the residence time of nasal gel of candesartan cilexitil for hypertension is of potential application and compliance.

Study of polysaccharide gels at Prof. Nishinari's laboratory

Studies performed at Prof. Katsuyoshi Nishinari's laboratory are overviewed. The gelation and gel properties of gellan gum were investigated by rheological and thermal analyses. The change in the elastic modulus of gellan gum gels due to the temperature or immersion in salt solutions was interpreted from the model that Prof. Nishinari proposed. The fracture behavior of the large deformation of gellan gum gels was also explained by this model. The gel of xyloglucan from tamarind seed, in particular, a thermoreversible cold-setting gel that formed in the presence of epigallocatechin gallate or Na-type gellan, was studied. As examples of recent collaborative works with Prof. Nishinari, the gelation of β-glucan extracted from Sparassis crispa, an edible mushroom, and the application of sodium alginate and low methoxy pectin to rice noodles are also described.

Thermoreversible Carbamazepine In Situ Gel for Intranasal Delivery: Development and In Vitro, Ex Vivo Evaluation.

Over the past decade, intranasal (IN) delivery has been gaining attention as an alternative approach to conventional drug delivery routes targeting the brain. Carbamazepine (CBZ) is available as an orally ingestible formulation. The present study aims to develop a thermoreversible in situ gelling system for delivering CBZ via IN route. A cold method of synthesis has been used to tailor and optimize the thermoreversible gel composition, using poloxamer 407 (P407) (15-20% w/v) and iota carrageenan (ɩ-Cg) (0.15-0.25% w/v). The developed in situ gel showed gelation temperatures (28-33°C), pH (4.5-6.5), rheological properties (pseudoplastic, shear thinning), and mucoadhesive strength (1755.78-2495.05 dyne/cm2). The in vitro release study has shown sustained release behavior (24h) for gel, containing significant retardation of CBZ release. The release kinetics fit to the Korsmeyer-Peppas model, suggesting the non-Fickian diffusion type controlled release behavior. Ex vivo permeation through goat nasal mucosa showed sustained release from the gel containing 18% P407 with the highest cumulative drug permeated (243.94µg/cm2) and a permeation flux of 10.16µg/cm2/h. After treatment with CBZ in situ gel, the barrier function of nasal mucosa remained unaffected. Permeation through goat nasal mucosa using in situ gel has demonstrated a harmless nasal delivery, which can provide a new dimension to deliver CBZ directly to the brain bypassing the blood-brain barrier.

Sugar-Based Phase-Selective Supramolecular Self-Assembly System for Dye Removal and Selective Detection of Cu2+ Ions.

Simple, effective, and eco-friendly sugar-based phase-selective gelators were synthesized at a low cost. They showed high gelling ability toward a wide range of solvents at lower concentrations (minimum gelation concentration ∼0.3%). Preliminary tests reveal that these low molecular weight organogelators can immediately and phase-selectively gel benzene, toluene, petrol, and kerosene in water at room temperature. We also identified G13 in toluene as the good gelator, and the corresponding organogel proficiently removes water-soluble dyes from their concentrated aqueous solutions. This efficient removal of toxic organic solvents and dyes from water suggests promising applications in removing organic substances from contaminated water resources. The thermoreversible gel exhibits effective rechargeability up to five cycles of burning and gelation, which imply the flame stability of the gel. Interestingly, these compounds had a high detection ability toward Cu2+ ions with a state change from gel to the solution. The physical justification for gelation mechanisms and the molecular interaction with metal ions were further confirmed by computational studies.

An in vitro assessment of the thermoreversible PLGA-PEG-PLGA copolymer: Implications for Descemet's membrane endothelial keratoplasty.

To explore the use of a thermoreversible copolymer gel coating to prevent donor tissue scrolling in Descemet's membrane endothelial keratoplasty (DMEK). PLGA-PEG-PLGA triblock copolymer was synthesised via ring opening polymerisation. Two formulations were fabricated and gelation properties characterised using rheological analyses. Endothelial cytotoxicity of the copolymer was assessed using a Trypan Blue exclusion assay. Thickness of the copolymer gel coating on the endothelial surface was analysed using anterior segment optical coherence tomography (OCT) (RTVue-100, Optovue Inc.). Gold nanoparticles were added to the copolymer to aid visualisation using OCT. Prevention of Descemet membrane donor scrolling was represented via a novel, in vitro, immersion of copolymer coated donor graft material. Two different formulations of PLGA-PEG-PLGA copolymer were successfully fabricated and the desired peak gelling temperature of 24°C was achieved by polymer blending. Application of 20%, 30% and 40% (wt/vol) polymer concentrations resulted in a statistically significant increase in polymer thickness on the endothelium (p < 0.001). There was no detectable endothelial cytotoxicity. The polymer was easy to apply to the endothelium and prevented scrolling of the DMEK graft. This PLGA-PEG-PLGA thermoreversible copolymer gel could be exploited as a therapeutic aid for preventing DMEK graft scrolling.

Research progress in the preparation, structural characterization, bioactivities, and potential applications of sulfated agarans from the genus Gracilaria.

The genus Gracilaria produces 80% of the world's industrial agar. Agar of this genus is a promising biologically active polymer, which has been used in the human diet and folk medicine, alternative for weight loss, treatment of diarrhea, etc. With more attention paid to the genus Gracilaria-sulfated agarans (GSAs), they exhibited multitudinous health benefits in antioxidant, antiviral, antibacterial, prebiotics, anti-tumor, anticoagulant, and antidiabetic. Various preparation procedures of GSAs making the diversities of structure and biological activity. Therefore, this review summarized the isolation, identification, bioactivity potentials, and applications of GSAs, providing a reference to the development of GSAs in functional food and pharmaceutical industry. PRACTICAL APPLICATIONS: The genus Gracilaria is known as a raw material for agar extraction. GSAs are food-grade agaran with the properties of thermoreversible gels at low concentrations, which are commonly used as an additive for making candies as well as raw material for making soup and snacks. They are used in folk medicine to treat diarrhea and other diseases. As an important bioactive macromolecule, GSAs have various biological activities (such as antioxidant, antiviral, antibacterial, probiotic, anti-tumor, anticoagulant, and antidiabetic activities), and have the potential to be developed as functional food and medicine. They could also be used to create innovative agar-based products such as antibacterial films and drug carriers.

Synthesis and Self-assembly of Novel Nanofeather-like Fluorescent Alkyloxy-Containing Diphenyl Ether Organogelators.

In this study, novel fluorescent low molecular-weight organogelators are derived from diphenyl ethers and substituted with para-alkoxy groups of different aliphatic chain lengths. The present research promotes the preparation of innovative nanofeather-like assemblies from the synthesized diphenyl ether-derived organogelators. The gelation performance of the prepared alkoxy-substituted diphenyl ethers was reported. The synthesis procedure was achieved by using a base-catalyzed reaction of hydroxyl-substituted diphenyl with various alcohols of different aliphatic chain lengths. The chemical structures of the synthesized diphenyl ether derivatives were studied by 1H/13C NMR and infrared spectroscopy. Fluorescence and UV–vis absorption spectral analyses showed solvatochromism. The diphenyl ether derivatives with longer alkoxy terminal substituents showed enhanced thermoreversible gelation activity as compared to the diphenyl ether derivatives with shorter alkoxy terminal substituents. The morphological properties of the self-assembled diphenyl ethers were studied by transmission electron microscopy and scanning electron microscopy, which showed supramolecular architectures of highly ordered nanofeathers, enforced by van der Waals interactions and π-stacks. Depending on the length of the aliphatic tail, different morphologies were detected, including nanofeathers, nanofibers, and nanosheets. The antimicrobial and cytotoxic properties of the prepared diphenyl ether-derived organogelators were examined to confirm their possible use in various fields like drug delivery systems.

Comparative Study on the Models of Thermoreversible Gelation.

A critical survey on the various theoretical models of thermoreversible gelation, such as the droplet model of condensation, associated-particle model, site–bond percolation model, and adhesive hard sphere model, is presented, with a focus on the nature of the phase transition predicted by them. On the basis of the classical tree statistics of gelation, combined with a thermodynamic theory of associating polymer solutions, it is shown that, within the mean-field description, the thermoreversible gelation of polyfunctional molecules is a third-order phase transition analogous to the Bose–Einstein condensation of an ideal Bose gas. It is condensation without surface tension. The osmotic compressibility is continuous, but its derivative with respect to the concentration of the functional molecule reveals a discontinuity at the sol–gel transition point. The width of the discontinuity is directly related to the amplitude of the divergent term in the weight-average molecular weight of the cross-linked three-dimensional polymers. The solution remains homogeneous in the position space, but separates into two phases in the momentum space; particles with finite translational momentum (sol) and a network with zero translational momentum (gel) coexist in a spatially homogeneous state. Experimental methods used to detect the singularity at the sol–gel transition point are suggested.

Thermoreversible gel of green tea extract: Formulation and evaluation for the management of periodontitis

Plant products have been extensively investigated for their application in the treatment of periodontitis owing to their therapeutic benefits with no major side effects. Further, increasing antimicrobial resistance associated with a constant intake of synthetic antimicrobials has led to a change in paradigm towards the use of phytochemical based formulations as antimicrobial therapy in periodontitis. With this background, our present investigation focuses on developing a novel thermoreversible gel of green tea extract (GT) which is well known for its antimicrobial and antioxidant potential. In the first stage, the antimicrobial activity of GT was assessed against a panel of microbes (S. mutans, P. gingivalis, P. intermedia, F. nucleatum and A. actinomycetemcomitans). Antimicrobial activity of GT extract showed MBC value of 1.25 w/v % with desirable antiadhesion (34–69%) and antibiofilm activity (47–69%). In time kill assay, GT demonstrated time dependent killing varying sensitivity against tested pathogens. In the second stage, based on the MBC value, the thermoreversible gel of GT (GTTG) was formulated using thermosensitive polymer poloxamer 407 (19.5% w/v) and mucoadhesive polymer carbopol 934 (0.4%w/v). Formulated GTTG showed gelation temperature of 29 ± 1 °C, gelation time of 44.67 ± 1.15 s, gelation strength of 45 ± 1 g, the viscosity of 1659 ± 86 cPs and mucoadhesive strength of 1960 dyne/cm2. GTTG showed maximum release and permeation of marker phytochemical Epigallocatechin gallate in 48 and 96 h respectively. Finally, formulated GTTG when compared with gold standard antiplaque agent chlorhexidine gel for its antimicrobial potential showed greater zone of inhibition (ZOI) when tested against key periodontal pathogen P. gingivalis. Hence, the formulated novel GTTG could serve as an effective alternative local drug delivery with ease of administration and accurate dosing for the treatment of periodontitis.