Search Results (127)

Background/Objectives: Supramolecular hydrogels formed by low-molecular-weight gelators present a chemically heterogeneous transport environment whose molecular-scale dynamics remain poorly understood. This study aimed to investigate how drug physicochemistry governs transport within a liquid-crystalline C18ADPA hydrogel at the molecular scale. Methods: Pulsed-field gradient NMR spectroscopy was used to measure self-diffusion coefficients of five model drugs (5-fluorouracil, acetylcholine, paracetamol, prednisolone, and amphotericin B) spanning a broad range of size, polarity, and charge state, in both free solution and the hydrogel matrix at pH 5.37. Results: Observed drug diffusion coefficients deviated substantially from classical obstruction theory predictions, demonstrating that transport is governed by host–guest chemical affinity rather than molecular size. The three water-soluble drugs exhibited bimodal diffusion, with relative amplitudes providing a direct estimate of bound and free drug fractions. Prednisolone co-diffused with the gelator scaffold, consistent with hydrophobic bilayer partitioning, while amphotericin B diffused at rates consistent with the structured interfacial water layer. The gel pH (5.37) emerged as an active determinant of transport: drug charge states at this pH from permanent cation (acetylcholine) to near-zwitterion (amphotericin B) correlated directly with the observed transport behavior. The near-zwitterionic character of amphotericin B at pH 5.37, arising from its carboxyl pKa (~5.5), suggests a previously unreported electrostatic interfacial trapping mechanism. Conclusions: The liquid-crystalline bilayer architecture creates chemically distinct microdomains that selectively recruit drugs based on hydrophobicity, hydrogen-bonding capacity, and pH-dependent charge state, providing a molecular-scale framework for rational formulation design in supramolecular drug delivery. Full article

Low-molecular-weight gelators (LMWGs) have attracted growing attention as versatile alternatives to conventional polymeric thickeners and gelators, owing to their ability to form three-dimensional fibrillar networks through non-covalent self-assembly and to undergo reversible sol–gel transitions in response to external stimuli. Among the various stimuli that can be exploited, pH represents a particularly attractive trigger given its direct relevance to biological and physiological environments. This review focuses on three categories of pH-responsive LMWGs that have shown notable progress over the past decade yet remain relatively underexplored in the literature. First, N-oxide-type hydrogelators are discussed, with emphasis on amide amine oxide-based surfactants and pyridine-N-oxide frameworks. The pH-dependent protonation of the N-oxide moiety modulates intermolecular hydrogen bonding, thereby governing self-assembly and gel formation. The structural versatility of these gelators enables rational tuning of aggregate morphology and confers clear pH and temperature responsiveness. Second, recent advances in phenylboronic acid-based LMWGs are highlighted. Although boronic acid derivatives have long been studied as dynamic crosslinking units in polymeric hydrogels, 3-isobutoxyphenylboronic acid was recently identified as the first example of phenylboronic acid functioning as an LMWG, in which gelation is driven primarily by hydrogen bonding and pH responsiveness is exploited for stimuli-triggered gel disruption rather than gel formation. Third, pH-responsive orthogonal self-assembly systems are reviewed. Representative examples include multicomponent hybrid hydrogels combining pH-activated LMWGs with polymer gelators for controlled drug release, pH-triggered self-sorting of two LMWGs without any polymeric component, and bio-based orthogonal hydrogels composed of a glucolipid LMWG and cellulose nanocrystals. For each system, both advantages and remaining limitations are critically assessed. Collectively, this review aims to provide a timely overview of emerging trends in pH-responsive LMWG research and to offer perspectives on the rational design of next-generation stimuli-responsive soft materials. Full article

The development of new advanced functional materials from low-molecular-weight gelators and their new potential applications have occupied a considerable place in research. The present study involves the design of dipeptide-based organogelators with enhanced hydrogen bonding network potentials and phase-selective capacities, possessing a minimum gelation concentration of 0.2–0.4% w/v in different fluids. Seven new dipeptide organogelators were prepared based on a one-step reaction from two-component salt forms, the combination of Nε-alkanoyl-L-lysine ethyl ester with N-alkanoyl-L-amino acids (L-alanine, L-leucine, and L-phenylalanine), with high yields of up to 90. All the gel materials were extremely stable at room temperature, having a shelf life of several months, and formed gels in pharmaceutical fluids such as ethyl palmitate, ethyl myristate, and ethyl laurate, 1,2-propanediol, and liquid paraffin (oils widely used in pharmaceutical formulations), which meet the criteria of biological materials delivery. Their gelation properties were evaluated by rheological measurements. A very significant breakthrough in the current study is that organogels remove the toxic dye, crystal violet (CV), from water in a phase-selective manner with an extremely low gelator concentration. The dye and gelators are successively recovered via ethanol precipitation after the completion of the phase extraction process. Molecular dynamic calculations provide evidence for the 3D structures of the gels. Full article

Limited mechanical robustness and prompt proteolytic degradation preclude wider biomedical application of supramolecular peptide hydrogels. Low-molecular-weight dehydropeptides represent a promising class of hydrogelators, owing to their enhanced proteolytic stability, high self-assembly propensity, biocompatibility, and tunable rheological and drug-release properties. Herein, we prepared a small library of N-succinylated dehydrotripeptides (Suc-L-Xaa-L-Phe-Z-ΔPhe-OMe/-OH; Xaa = Phe or Val), together with the canonical analogs (Suc-L-Phe-L-Phe-L-Phe-OMe/-OH), to assess whether in addition to proteolytic resistance, dehydropeptides offer clear advantages over canonical peptides in terms of self-assembly, gelation efficacy, mechanical performance, and cargo release. Peptide self-assembly, hydrogel formation, and supramolecular organization were investigated by fluorescence and circular dichroism (CD) spectroscopy, molecular dynamic (MD) simulations, Thioflavin T hydrogel staining, ATR-FTIR spectroscopy, transmission electron microscopy (TEM), and rheological measurements. Drug-release performance was evaluated using methyl orange as a model cargo. Overall, the dehydropeptide-based hydrogels displayed enhanced gelation efficacy, improved mechanical properties, and sustained release profiles compared to canonical analogs. Spectroscopic analysis (CD and ATR-FTIR) and molecular dynamic simulations indicated that the dehydropeptides preferentially self-assemble into more ordered supramolecular fibrils, with extended β-sheet-like packing, whereas the canonical peptides predominantly populate more disordered backbone environments. Proteolysis assays with α-chymotrypsin revealed that both canonical and dehydropeptide methyl esters underwent chymotrypsin-catalyzed ester hydrolysis. Importantly, only the canonical dicarboxylic acid underwent further proteolytic degradation. The dehydropeptide dicarboxylic acids revealed fully resistant to proteolysis over extended time periods. These results demonstrate that the incorporation of dehydroamino acid into peptides enables control over supramolecular packing, nanofibrillar network architecture, rheology, and cargo release. This report raises the profile of relatively underexplored dehydropeptide-based soft materials as promising high-performance biomaterials for technological and biomedical applications. Full article

Biopolymers and bioactive peptides of plant origin represent sustainable resources with high potential for the development of functional ingredients with health benefits. An underutilized plant source of antihypertensive peptides is lima bean protein (Phaseolus lunatus); however, these peptides can be inactivated or degraded during their passage through the gastrointestinal tract. This study evaluated chia (Salvia hispanica) mucilage (CM) combined with sodium alginate (Al) as a hybrid encapsulation matrix for ACE-inhibitory peptides (<10 kDa) from P. lunatus. The ionic gelation technique was used, and encapsulation conditions were optimized using a 2³ factorial design that evaluated CM:Al ratios, calcium concentration, and hardening time. The optimal formulation (30:70 CM:Al; 0.05 M CaCl₂; 20 min of hardening time) achieved approximately 48% encapsulation efficiency and maintained the peptides’ ACE-inhibitory (IC₅₀ mg/mL) activity during simulated gastric digestion with controlled intestinal release. The formed capsules demonstrated good flow properties, thermal stability up to 178 °C, and preserved ACE-I activity (0.1 mg/mL IC₅₀) significantly better than alginate alone after in vitro digestion. These findings suggest that CM:Al blends could produce capsules with the ability to protect bioactive peptides with low molecular weight, warranting further investigation through in vivo bioavailability studies and structural characterization to confirm the proposed matrix-enhancing mechanisms. Full article

Slickwater fracturing has become an adopted technology for enhancing hydrocarbon recovery from unconventional, low-permeability reservoirs such as shale and tight formations, owing to its ability to generate complex fracture networks at a low cost. Polyacrylamide and polyacrylamide-based gels serve as key additives in these fluids, primarily functioning as drag reducers and thickeners. However, downhole environments of high-temperature (>120 °C) and high-salinity (>1 × 10⁴ mg/L) reservoirs pose challenges, leading to thermal degradation and chain collapse of conventional polyacrylamide, which results in performance loss. To address these limitations, synthesis methods including aqueous solution polymerization, inverse emulsion polymerization, and aqueous dispersion polymerization have been developed. This review provides an overview of molecular design methods aimed at enhancing performance stability of polyacrylamide-based polymers under extreme conditions. Approaches for improving thermal stability involve synthesis of ultra-high-molecular-weight polyacrylamide, copolymerization with resistant monomers, and incorporation of nanoparticles. Methods for enhancing salt tolerance focus on grafting anionic, cationic, or zwitterionic side chains onto the polymer backbone. The drag reduction mechanisms and gelation methods of these polymers in slickwater fracturing fluids are discussed. Finally, this review outlines research directions for developing next-generation polyacrylamide polymers tailored for extreme reservoir conditions, offering insights for academic research and field applications. Full article

Gel-based depots are increasingly recognized as platforms to extend the intratissue residence of local anesthetics (LAs) while reducing systemic exposure. Hydrogels, organogels, and emerging bigels represent three distinct architectures defined by their continuous phases and drug–matrix interactions. Hydrogels provide hydrated polymer networks with predictable injectability, tunable degradation, and diffusion- or stimulus-responsive release, enabling sustained analgesia in perineural, peri-incisional, intra-articular, and implant-adjacent settings. Organogels, formed by supramolecular assembly of low-molecular-weight gelators in lipids or semi-polar solvents, strongly solubilize lipophilic LA bases and enhance barrier partitioning, making them suitable for dermal, transdermal, and mucosal applications in outpatient or chronic pain care. Bigels integrate aqueous and lipid domains within biphasic matrices, improving rheology, spreadability, and dual-solubilization capacity, although their use in LA delivery remains at the formulation stage, with no validated in vivo pharmacology. This narrative review synthesizes the design principles, release mechanisms, and translational evidence across these platforms, highlighting domain-specific advantages and barriers related to mechanical robustness, sterilization, reproducibility, and regulatory feasibility. We propose a platform-level framework in which depot selection is aligned with LA chemistry, anatomical context, and clinical objectives to guide the development of workflow-compatible next-generation LA depots. Full article

Supramolecular hydrogels formed by the self-assembly of low-molecular-weight (LMW) agents are promising next-generation biomaterials for drug delivery, tissue engineering, and regenerative medicine. Phenylalanine (Phe) derivatives have emerged as a privileged class of LMW supramolecular gelators due to their strong propensity to self-assemble into emergent hydrogel networks with demonstrated biocompatibility. We have previously reported a series of cationic Phe-derived gelators in which fluorenylmethoxycarbonyl (Fmoc) phenylalanine (Phe), 3-fluorophenylalanine (3F-Phe), and pentafluorophenylalanine (F₅-Phe) are functionalized at the C-terminus with diaminopropane (DAP). These gelators (Fmoc-Phe-DAP, Fmoc-3F-Phe-DAP, and Fmoc-F₅-Phe-DAP) are water-soluble and undergo spontaneous self-assembly and gelation upon an increase in the ionic strength of the solution caused by addition of sodium chloride. Herein, we report the effects of pH on the self-assembly and gelation of Fmoc-Phe-DAP, Fmoc-3F-Phe-DAP, and Fmoc-F₅-Phe-DAP. We also describe the effects that pH has on the emergent properties of these hydrogel networks, including assembly morphology and hydrogel viscoelasticity. These studies indicate that pH has varying effects on the properties of the hydrogels that are also dependent on the molecular structure of the Fmoc-Phe-DAP derivative. Fmoc-Phe-DAP hydrogels are highly sensitive to changes in solvent pH, forming strong hydrogels only near neutral pH. In contrast, hydrogels of Phe derivatives with fluorinated side chains (Fmoc-3F-Phe-DAP and Fmoc-F5-Phe-DAP) have consistent emergent viscoelastic properties across a wider range of acidic to basic pH values. Full article

Polyacrylamide and polyacrylamide/polysaccharide hydrogels exhibiting high structural and mechanical properties, along with acceptable gelation times and gelant viscosity, are proposed for water shutoff applications in high-temperature reservoirs. The obtained polyacrylamide gels demonstrate an elastic modulus 1.6–2.7 times higher than that of the baseline polyacrylamide–resorcinol–paraform–sulfamic acid gel (17.2 Pa), reaching up to 46.3 Pa, while the polyacrylamide/polysaccharide gels surpass it by a factor of 2.3–5.2, reaching up to 89.9 Pa. The gelation time of the polyacrylamide/polysaccharide gels ranges from 3 to 7 h, with the gelant viscosity varying from 685 to 2098 mPa·s at a shear rate of 100 s⁻¹. Crosslinking of polyacrylamide with polysaccharides was achieved using paraform. Using the gel based on crosslinked polyacrylamide with xanthan as an example, spectral methods characterized the copolymer constituting the basis of the plugging material. Our analysis established that crosslinking occurs between the amide group of polyacrylamide and the hydroxyl group of the polysaccharide. Model reactions with low-molecular-weight analogs (glucose, acetamide, and formaldehyde), coupled with mass spectrometric confirmation of the structure of the resulting products, revealed possible reaction pathways. The crosslinking of polyacrylamide was investigated using a broad range of polysaccharides of plant and microbiological origin. The resulting series of hydrogels, possessing the suite of properties required for water shutoff in high-temperature formations, will enable oil companies (operators) and service firms to select a specific gel-forming system based on project objectives, logistics, and budget constraints. Full article

To address the issues of traditional gels in high-temperature reservoir leakage plugging, such as injection–retention imbalance, poor high-temperature stability, and insufficient thixotropy, this study developed a thixotropic polymer gel system via molecular design and component optimization, aiming to achieve excellent thixotropy, high strength, and wide temperature adaptability (80–140 °C) while clarifying its gelation mechanism. First, the optimal polymer was selected by comparing the high-temperature stability and crosslinking activity of AM/AMPS copolymer (J-2), low-molecular-weight acrylamide polymers (J-3, J-4), and AM/AMPS/NVP terpolymer (J-1). Then, the phenolic crosslinking system was optimized: hexamethylenetetramine (HMTA) was chosen for controlled aldehyde release (avoiding poor stability/dehydration) and catechol for high crosslinking efficiency (enhancing strength via dense crosslinking sites). Urea–formaldehyde resin (UF) was introduced to form a “polymer-resin double network,” improving high-temperature compression resistance and long-term stability. Cyclic shear rheological tests showed the gel system had a larger hysteresis area than the polymer solution, indicating excellent thixotropy before gelation. It gelled completely at 80–140 °C (gelation time shortened with temperature). At 120 °C, its viscosity was 7500 mPa·s, storage modulus (G′) 51 Pa, and loss modulus (G″) 6 Pa, demonstrating good shear thixotropy. The final system (1% J-1, 0.3% catechol, 0.6% HMTA, 15% UF) is suitable for high-temperature reservoir leakage plugging. Full article

Introduction. Larvae of the insect Hermetia illucens can represent an alternative source for low-molecular-weight chitosan (CS) production compared with CS from crustaceans (CS_crustac), making it appealing in terms of pharmaceutical applications. Hence, the performances of CS_larvae and CS_crustac were compared herein by investigating the in vitro features of nanoparticles (NPs) made from each polysaccharide and administered with the antioxidant quercetin (QUE). Methods. X-ray diffraction and FT-IR spectroscopy enabled the identification of each type of CS. Following the ionic gelation technique and using sulfobutylether-β-cyclodextrin as a cross-linking agent, NPs were easily obtained. Results. Physicochemical data, release studies in PBS, and the evaluation of antioxidant effects via the 1,1-diphenyl-2-picrylhydrazyl (DPPH) test were studied for both CS_larvae and CS_crustac. QUE-loaded NP sizes ranged from 180 to 547 nm, and zeta potential values were between +7.5 and +39.3 mV. In vitro QUE release in PBS was faster from QUE-CS_larvae NPs than from CS_crustac, and high antioxidant activity—according to the DPPH test—was observed for all tested NP formulations. Discussion. The agar diffusion assay, referring to Escherichia coli and Micrococcus flavus, as well as the microdilution assay, showed the best performance as antimicrobial formulations in the case of QUE-CS_larvae NPs. QUE-CS_larvae NPs can represent a promising vehicle for QUE, releasing it in a sustained manner, and, relevantly, the synergism noticed between QUE and CS_larvae resulted in a final antimicrobial product. Conclusions. New perspectives for low-molecular-weight CS are disclosed by adopting renewable sources from insects instead of the commercial CS_crustac. Full article

The broader application of gluten in both the food and non-food industries is limited by its lack of functional properties, such as solubility, foaming ability, and rheological characteristics. This study aimed to evaluate the physicochemical properties of proteins in various gluten products and to investigate the effects of enzymatic hydrolysis and ultrasound (US) treatment on wheat flour gluten yield, gliadin–glutenin complex structure, and gelation properties. The gelation properties of wheat gluten (GL)/pea protein (PP) treated with US and transglutaminase (TG) were studied. The results demonstrated that the ratio of low- to high-molecular-weight components in gliadins and glutenins significantly influenced the quality of commercial gluten products. A 90 min treatment of wheat flour with 24 TGU/100 g increased the yield of high-quality gluten by 32% while reducing the gliadin content by up to 6-fold. Additionally, a 30 min US treatment of 18–20% pure gluten suspensions yielded a sufficiently strong gel. The addition of PP isolate (80% protein) improved the texture of gluten gels, with the best results observed at a GL:PP ratio of 1:2. The application of TG increased the hardness, consistency, and viscosity of GL-PP gels by an average of 5.7 times while reducing stickiness. The combined TG and US treatments, along with the addition of PP, notably increased the levels of lysine, isoleucine, and tryptophan, thereby enhancing both the nutritional quality and amino acid balance of the final product. Full article

Hot-pressing densification is an effective method to enhance the mechanical properties of wood; however, excessively high pressing temperatures can cause thermal degradation of wood components, compromising these improvements. In this study, aminated lignin (AL), with improved water solubility and reactive amino groups facilitating crosslinking, was utilized as a bio-based amine curing agent for the water-soluble, low-molecular-weight epoxy compound polyethylene glycol diglycidyl ether (PEGDGE). The PEGDGE-AL modifier was applied for wood impregnation, followed by hot-pressing densification at a relatively low temperature of 120 °C, to enhance the mechanical properties of wood. The chemical composition of AL was analyzed using Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), and X-ray photoelectron spectroscopy (XPS). The gelation and curing behavior of the PEGDGE-AL modifier demonstrated its ability to readily form a network structure at both room temperature and elevated temperatures. The impact strength of densified wood (DW) modified with 12 wt% PEGDGE and 8 wt% AL, denoted as 12PEGDGE+8AL-DW, exhibited an impact strength of 15.2 kJ/m², representing a 72% increase compared to untreated wood (UW). The modulus of rupture (MOR) and modulus of elasticity (MOE) reached 241.1 MPa and 14.6 GPa, respectively, corresponding to 60% and 75% improvements over UW. Furthermore, the 24 h water uptake and thickness swelling of 12PEGDGE+8AL-DW were 45.2% and 24.7%, which were 11% and 43% lower than those of water-impregnated and hot-pressed densified wood (W-DW), respectively. This study provides a low-temperature route for wood densification while contributing to the valorization of lignin in high-performance material applications. Full article

This study presents the formulation and evaluation of a dual molecular weight polymer gel system composed of partially hydrolyzed polyacrylamide (HPAM) and crosslinked with polyethyleneimine (PEI) for water shut-off applications. A soft gel, designed for deep reservoir penetration, was formulated using 5000 ppm high-molecular-weight HPAM, while a rigid gel for near-wellbore blockage combined 5000 ppm high- and 5000 ppm low-molecular-weight HPAM. The gel system was designed at 65 °C, with an initial gelation time exceeding 8 h and viscosity values below 15 cP before gelation, ensuring ease of injection. Laboratory assessments included bottle testing, rotational and oscillatory rheological measurements, and core flooding to determine residual resistance factors (RRFs). The soft gel achieved a final strength of Grade D (low mobility), while the rigid gel reached Grade G (moderate deformability, immobile), according to Sydansk’s classification. RRF values reached 93 for the soft gel and 185 for the rigid gel, with both systems showing strong washout resistance and water shut-off efficiencies above 95%. These results demonstrate the potential of the HPAM/PEI gel system as an effective solution for conformance control in mature reservoirs with active aquifers. Full article

Cosmetic formulations are complex mixtures of ingredients that must fulfill several requirements. One of the challenges of the cosmetic industry is to find natural alternatives to replace synthetic polymers, preserving desirable sensory characteristics. The aim of this work is to induce the formation of gels, by replacing synthetic polymers with a low-molecular-weight gelator (LMWG), a small molecule able to self-assemble and form supramolecular networks. The impact of low-molecular-weight gelators on the environment is reduced as they are highly biodegradable. Thus, the behavior of solutions containing Boc-L-Dopa(Bn)₂-OH, an LMWG, together with ten different anionic surfactants, was studied to understand if the LMWG may act as a rheological modifier by increasing the viscosity of the formulation or forming gels with these ingredients. An amphoteric surfactant, cocamidopropyl betaine (CAPB), often used to increase cleansing gentleness, was also added to the solutions to better mimic a cosmetic formulation. In most cases, the addition of the gelator at only a 1% w/v concentration induces the gelification or an increase in the viscosity of the solutions, thus showing that this molecule is also able to self-assemble in complex mixtures. Full article