Critical Gelation Research Articles

Effect of targeting ligand designation of self-assembly chitosan-poloxamer nanogels loaded Paclitacel on inhibiting MCF-7 cancer cell growth

In this study, we investigated two formulations of chitosan-Pluronic P123 with different folate ligand designation for targeted delivery of Paclitaxel (PTX), in which folic acid (FA) was directly conjugated to chitosan (FA-Cs-P123) or substituted onto P123 (Cs-P123-FA). The results showed that the FA content of Cs-P123-FA was determined at 0.71 wt/wt% which was significantly higher than that of FA-Cs-P123 (0.31 wt/wt%). Two copolymers were low critical gel concentrations (CGC). FA-Cs-P123 and Cs-P123-FA nanogels performed high PTX encapsulation efficiency reaching 95.57 ± 5.51 and 92.51 ± 6.68 wt/wt%, respectively. Transmission electron microscopy (TEM) and zeta potential analysis indicated that the PTX-loaded nanogels were spherically formed around 60 nm in diameter along with positive charge. Furthermore, the PTX release profile was slow and it was controlled by the pH of the medium. In particular, in vitro biocompatibility assays indicated that both FA-Cs-P123 and Cs-P123-FA exhibited good biological compatibility with a human foreskin fibroblast cell line and well uptake efficiency into MCF-7 cancer cells. Cs-P123-FA nanogel significantly enhanced the cytotoxicity of PTX in comparison with FA-Cs-P123. The result indicates that Cs-P123-FA nanogels with a higher decorated FA content perform a better targeting efficiency; therefore, they could have great potential application towards breast cancer treatment.

Light-Induced In Situ Chain Extension and Critical Gelation of Benzophenone End-Functionalized Telechelic Associative Polymers in Aqueous Solution

Light-Induced In Situ Chain Extension and Critical Gelation of Benzophenone End-Functionalized Telechelic Associative Polymers in Aqueous Solution

Crucial Impact of Residue Chirality on the Gelation Process and Biodegradability of Thermoresponsive Polypeptide Hydrogels.

Thermosensitive polypeptide hydrogels have gained considerable attention in potential biomedical applications, of which the polymer structure may be tuned by residue chirality. In this study, polypeptide-based block copolymers with different chiralities were synthesized by ring-opening polymerization of γ-ethyl-l-glutamate N-carboxyanhydride and/or γ-ethyl-d-glutamate N-carboxyanhydride using amino-terminated monomethoxy poly(ethylene glycol) as a macroinitiator. All mPEG-polypeptide copolymers underwent sol-gel transition with an increase in temperature. The block copolymers with mixed enantiomeric residues of γ-ethyl-l-glutamate (ELG) and γ-ethyl-d-glutamate (EDG) in the polypeptide blocks exhibited lower critical gelation concentrations and lower critical gelation temperatures compared with those composed of pure ELG or EDG residues. We established that the difference in gelation properties between the copolymers was derived from the distinction of the secondary structures. We further demonstrated the influence of polypeptide chirality on the degradability and biocompatibility of hydrogels in vivo. Our findings provide insights into the design of hydrogels having tailored secondary conformation, gelation property, and biodegradability.

Triphenylamine derivative-based supramolecular self-assembly system for selective sensing methanol via hydrogen bonding

A novel gelator (TAPA) based on a triphenylamine derivative containing three pyridine groups was designed and synthesized, which could self-assemble into a gel in toluene and o-dichlorobenzene with their corresponding critical gel concentration of 25.0 and 3.12 mg mL−1. Yellow light emitting gel could be obtained, and generated clusters in the micron size range and nanofiber structures. The self-assembly process of TAPA in toluene and o-dichlorobenzene was studied by multiple technologies. Interesting, solutions TAPA in different solvents exhibited different emission behavior. Especially, the emission behavior was prohibited in alcohol solution and the emission quenching performance was enhanced with the alkyl chain of alcohol shortening. In view of this peculiarity, compound TAPA could detect methanol in solution and xerogel state. The limit of detection (LOD) of solution TAPA and xerogel TAPA towards methanol was low as 2.58 mg L1 and 26.68 ppb. NMR experiments and theoretical calculations revealed that the possible detection mechanism was the molecule structure transformation from the enol form to amide structure of TAPA under the inducing of methanol by intermolecular hydrogen bonding.

Thermostable fluorescent supramolecular gels constructed from a single gelator and its application in discriminating organic acids

In this work, 5,5′,5′′-(1,3,5-triazine-2,4,6-triyl)tris(azanediyl)triisophthalate (H6L) was used as a gelator to prepare thermostable supramolecular gels (H6L gels). The lowest critical gelation concentration of H6L was found to be only 0.14 wt%. H6L gels remained stable after being placed at 85 °C for 1 h, indicating that its gel-sol phase transition temperature (Tgel) was not<85 °C. H6L gels can be formed in just a few seconds in comparison with the longer gelation time of a conventional thermostable gel. Moreover, a thermostable H6L/Fe3+ gel was also prepared by the coordination interactions of H6L and Fe3+ ions. The studies of FT-IR, UV–vis, XRD and SEM reveal that multiple hydrogen bonds, π-π interactions as well as coordination interactions were the main driving forces for the formation of thermostable three-dimensional network structure of H6L gels. In addition, the fluorescence spectra of H6L gels showed that the dual emission at 396 nm and 469 nm was derived from the structure of melamine and 5-aminoisophthalic acid contained in H6L structure. The gel formed at high temperature had relatively high transparency and strong fluorescence signal, and the fluorescence intensity is affected by the external H+ concentration. Using this characteristic, 14 organic acids can be effectively identified with the help of principal component analysis (PCA). L-cysteine can be identified with the naked eye by the color and state changes of H6L/Fe3+ gels.

Molecular Engineering onto RuII Bis(1,2-diphenylphosphinoethane) Synthon: Toward an Original Organometallic Gelator

In this article, we report the successful molecular engineering of Ru bis-acetylides that led for the first time to a gelator and more specifically in aromatic solvents. By means of a nonlinear ligand and an extended aromatic platform, the bulky Ru bis-acetylides were able to self-assemble into lamellar structures as evidenced by scanning electron microscopy (SEM) in benzene, toluene, and o- and m-xylene, which in turn induced gelation of the solution with a critical gelation concentration of 30 mg/mL. Nuclear magnetic resonance (NMR), variable temperature (VT)-NMR, and Fourier transform infrared (FT-IR) spectroscopies evidenced that hydrogen bonds are mainly responsible for the self-organization. VT-NMR and small-angle X-ray scattering (SAXS) have also suggested that the pro-ligand and the complex stack in different ways.

Tungsten disulfide (WS2) doped polyacrylamide (PAAm) composites: Gelation and optical studies

The organic Acrylamide (AAm) copolymerization in various contents of inorganic WS2 has been reported. The aim was to investigate the effect of the WS2 amount on the obtained morphology and the gelation process of the AAm composites. It was found that during gelation process the photon intensity of transmission decreased significantly above some critical time, called the gel point, tg. The decrease in the photon intensity of transmission was related to the increase in the intensity of scattered light from the gel attributable to the production of microgel that occurs while copolymerization held in AAm with Bis-Acrylamide (BIS). Gel points were found to be increased by increasing WS2 content. Time-dependent scattering of composites manifests the growth mechanism, the greater microgel particles, as in agreement with Rayleigh’s equation of scattering. It is determined that concentration of microgels is inversely proportional to the WS2 content. The composite rate constants of gelation, kr were produced and observed that it is proportional to WS2 content. It is understood that inclusion of WS2 in AAm system during gelation delays the process at early times but then contributes to increase the gelation process by increasing the rate of polymerization. Besides less compact PAAm gels are produced in the presence of WS2 atoms. It is also shown that the microgel growth mechanism and gel point of PAAm composite incorporated with WS2 can be significantly tailored by the amount of WS2. Tunable growth mechanism and critical gelation point is crucial for flexible electronic applications.

A supramolecular host-guest interaction-mediated injectable hydrogel system with enhanced stability and sustained protein release

Injectable hydrogels have been studied as drug delivery systems because of their minimal invasiveness and sustained drug release properties. Pluronic F127, consisting of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers, exhibits thermo-responsive properties and hence is injectable due to its rapid sol-gel transition. Unmodified Pluronic F127-based hydrogels, however, have limited long-term stability and controllable release of drugs entrapped within them. In this study, host-guest interactions between adamantane-conjugated Pluronic F127 (F127-Ad) and polymerized β-cyclodextrin (CDP) were employed to develop a hydrogel-based protein delivery system. Single or multiple adamantane units were successfully introduced at the termini of Pluronic F127 with a 100% conversion yield, and the synthesized F127-Ad polymer produced a physically crosslinked micelle-packing structure when mixed with CDP. As the number of adamantanes at the terminal ends of Pluronic F127 increased, the critical gelation concentration of F127-Ad/CDP hydrogel decreased from 15 to 6% (w/v). The F127/CDP hydrogel was able to maintain its structure even with lower polymer content, and its injectability improved with a reduction of the hydrogel viscosity. The long-term stability of F127/CDP hydrogels was evaluated in vitro and in vivo, and it was demonstrated that the subcutaneously injected hydrogel did not disintegrate for up to 30 d. Throughout the drug release test using gelatin and insulin as model drugs, it was demonstrated that their release rates could be regulated via complexation between the protein drugs and the β-cyclodextrin molecules inside the hydrogel. In conclusion, the F127-Ad/CDP hydrogel is expected to be a versatile protein delivery system with controllable durability and drug release characteristics. Statement of significancePluronic F127 is one of the widely studied polymeric materials for thermo-sensitive injectable hydrogels due to its high biocompatibility and rapid sol-gel transition. Since the Pluronic F127-based hydrogel has some limitations in its long-term stability and mechanical property, it is inevitable to modify its structure for the application to drug delivery. In this study, mono- or multi- adamantane-conjugated Pluronic F127s were synthesized and mixed with β-cyclodextrin polymers to form hydrogels with host-guest interaction-mediated micelle-packing structures. The host-guest interaction introduced into the hydrogel system endowed it a sustained protein drug release behavior as well as high durability in vitro and in vivo. By increasing the number of adamantane molecules at the end of the Pluronic F127, both the stability and injectability of the hydrogel could be also modulated.

Nicotinamide-based supergelator self-assembling via asymmetric hydrogen bonding NH⋯OC and H⋯Br− pattern for reusable, moldable and self-healable nontoxic fuel gels

HypothesisDevelopment of highly efficient low-molecular weight gelators (LMWGs) for safe energy storage materials is of great demand. Energy storage materials as fuel gels are often achieved by construction of hybrid organic frameworks capable of multiple noncovalent interactions in self-assembly, which allow tuning required properties at the molecular level by altering individual building blocks of the LMWG. However, LMWGs have limited rechargeable capability due to their chemical instability. ExperimentsWe designed, synthesized and characterized a novel, bio-inspired chiral gemini amphiphile derivative 1 containing N-hexadecyl aliphatic tails from quaternized nicotinamide-based segment and bromide anion showing supergelation ability in water, alcohols, aprotic polar and aromatic solvents, with critical gel concentrations as low as 0.1 and 0.035 wt% in isopropanol and water, respectively. FindingsNanostructural architecture of the network depended on the solvent used and showed variations in size and shape of 1D nanofibers. Supergelation is attributed to a unique asymmetric NH⋯OC, H⋯Br− hydrogen bonding pattern between H-2 hydrogens from nicotinamide-based segment, amide functional groups from chiral trans-cyclohexane-1,2-diamide-based segment and bromide ions, supporting the intermolecular amide–amide interactions appearing across one strand of the self-assembly. Gels formed from 1 exhibit high stiffness, self-healing, moldable and colorable properties. In addition, isopropanol gels of 1 are attractive as reusable, shape-persistent non-toxic fuels maintaining the chemical structure with gelation efficiency for at least five consecutive burning cycles.

An Inverse Thermogelling Bioink Based on an ABA-Type Poly(2-oxazoline) Amphiphile.

Hydrogels are key components in several biomedical research areas such as drug delivery, tissue engineering, and biofabrication. Here, a novel ABA-type triblock copolymer comprising poly(2-methyl-2-oxazoline) as the hydrophilic A blocks and poly(2-phenethyl-2-oxazoline) as the aromatic and hydrophobic B block is introduced. Above the critical micelle concentration, the polymer self-assembles into small spherical polymer micelles with a hydrodynamic radius of approx 8-8.5 nm. Interestingly, this specific combination of hydrophilic and hydrophobic aromatic moieties leads to rapid thermoresponsive inverse gelation at polymer concentrations above a critical gelation concentration (20 wt %) into a macroporous hydrogel of densely packed micelles. This hydrogel exhibited pronounced viscoelastic solid-like properties, as well as extensive shear-thinning, rapid structure recovery, and good strain resistance properties. Excellent 3D-printability of the hydrogel at lower temperature opens a wide range of different applications, for example, in the field of biofabrication. In preliminary bioprinting experiments using NIH 3T3 cells, excellent cell viabilities of more than 95% were achieved. The particularly interesting feature of this novel material is that it can be used as a printing support in hybrid bioink systems and sacrificial bioink due to rapid dissolution at physiological conditions.

Sol-Gel Transition and Critical Gel in Vulcanization Reaction

Academic Journal of Polymer science (AJOP) is a Journal which publishes state-of-the-art overview articles by internationally recognized authorities in polymer science and engineering. It covers all the areas of particular interest are biomedical applications,

Physical Aspects of Organogelation: A Point of View.

The physics side of organogelation is broached through three main aspects, thermodynamics (formation and melting), structure (morphology and molecular organization), and rheology. A definition of a gel is first discussed so as to delimit the field of investigation; namely, systems constituted of fibril-like entities. It is again highlighted that gel formation occurs through first-order transitions, chiefly by homogeneous nucleation. A deeper knowledge of the system is thus achieved by mapping out the temperature–concentration phase diagram. Some experimental diagrams are shown, while diagrams likely to pertain to these systems are presented. The molecular arrangement is basically crystallization that occurs in a preferred direction, hence the formation of fibrils. The effects of the solvent type, the quenching process of the solution are discussed with respect to the morphology and the crystal structure. Finally, the rheological properties are tackled. Notions of critical gelation concentration and percolation are debated. The interest of mapping out the temperature–concentration phase diagram is emphasized, particularly for understanding the variation of the gel modulus with temperature.

Bolaamphiphilic Bis-Dehydropeptide Hydrogels as Potential Drug Release Systems

The self-assembly of nanometric structures from molecular building blocks is an effective way to make new functional materials for biological and technological applications. In this work, four symmetrical bolaamphiphiles based on dehydrodipeptides (phenylalanyldehydrophenylalanine and tyrosyldehydrophenylalanine) linked through phenyl or naphthyl linkers (terephthalic acid and 2,6-naphthalenedicarboxylic acid) were prepared, and their self-assembly properties were studied. The results showed that all compounds, with the exception of the bolaamphiphile of tyrosyldehydrophenylalanine and 2,6-naphthalene dicarboxylic acid, gave self-standing hydrogels with critical gelation concentrations of 0.3 wt % and 0.4 wt %, using a pH trigger. The self-assembly of these hydrogelators was investigated using STEM microscopy, which revealed a network of entangled fibers. According to rheology, the dehydrodipeptide bolaamphiphilic hydrogelators are viscoelastic materials with an elastic modulus G′ that falls in the range of native tissue (0.37 kPa brain–4.5 kPa cartilage). In viability and proliferation studies, it was found that these compounds were non-toxic toward the human keratinocyte cell line, HaCaT. In sustained release assays, we studied the effects of the charge present on model drug compounds on the rate of cargo release from the hydrogel networks. Methylene blue (MB), methyl orange (MO), and ciprofloxacin were chosen as cationic, anionic, and overall neutral cargo, respectively. These studies have shown that the hydrogels provide a sustained release of methyl orange and ciprofloxacin, while methylene blue is retained by the hydrogel network.

Time–connectivity superposition and the gel/glass duality of weak colloidal gels

Colloidal gels result from the aggregation of Brownian particles suspended in a solvent. Gelation is induced by attractive interactions between individual particles that drive the formation of clusters, which in turn aggregate to form a space-spanning structure. We study this process in aluminosilicate colloidal gels through time-resolved structural and mechanical spectroscopy. Using the time-connectivity superposition principle a series of rapidly acquired linear viscoelastic spectra, measured throughout the gelation process by applying an exponential chirp protocol, are rescaled onto a universal master curve that spans over eight orders of magnitude in reduced frequency. This analysis reveals that the underlying relaxation time spectrum of the colloidal gel is symmetric in time with power-law tails characterized by a single exponent that is set at the gel point. The microstructural mechanical network has a dual character; at short length scales and fast times it appears glassy, whereas at longer times and larger scales it is gel-like. These results can be captured by a simple three-parameter constitutive model and demonstrate that the microstructure of a mature colloidal gel bears the residual skeleton of the original sample-spanning network that is created at the gel point. Our conclusions are confirmed by applying the same technique to another well-known colloidal gel system composed of attractive silica nanoparticles. The results illustrate the power of the time-connectivity superposition principle for this class of soft glassy materials and provide a compact description for the dichotomous viscoelastic nature of weak colloidal gels.

Gelation of Konjac glucomannan crosslinked by organotitanium chelated with different ligands

Konjac Glucomannan (KGM) gels can be formed in the presence of organotitanium as crosslinkers which were chelated by different organic compounds. Organotitanium cross-linking agent is a chelate formed by coordination between tetrabutyl titanate and different organic compounds. The gel network was formed through the crosslinking reaction between titanium ions dissociated from organotitanium crosslinkers and the cis-diol hydroxyl groups on the mannose units of polysaccharide chains. Effect of concentration and species of ligands on rheological properties of the complex gels was studied by dynamic viscoelastic measurements. The gelation kinetics of the gels were investigated and the critical gelation points of the gels were accurately determined according to the Winter-Chambon criterion. The effects of kinds and concentrations of ligands on the shear storage modulus (G’), the loss modulus (G”), and the sol-gel transition points were studied. The sol-gel transition time varies with different ligands in the organotitanium crosslinkers. The sol-gel transition time and temperature were obviously observed and in good agreement with Winter–Chambon criterion.

Stiff-Stilbene-Bridged Biscalix[4]arene as a Highly Light-Responsive Supramolecular Gelator.

A newly designed stiff-stilbene functionalized biscalix[4]arene in its cis form Z-1 could be near-quantitatively photoswitched to the trans-isomer E-1 under irradiation of 385 nm UV light. The trans-biscalix[4]arene E-1 was found to be a supergelator in nonpolar organic solvents, e.g., cyclohexane, hexane, pentane, and ether, with critical gelation concentrations as low as 0.2, 0.5, 0.5, and 0.4% w/v, respectively. The cis-trans configurational isomerism of biscalix[4]arene 1 resulted in distinct self-assembly modes, leading to interesting microscopic morphological changes from honeycomb and ringlike structures to rodlike dense fibrous networks.

Preparation and properties of the decomposable thermoreversible hydrogels based on novel dendritic crosslinkers derived from cystamine

Novel dendritic monomers derived from cystamine (Cy) were firstly synthesized in this research. Then, these monomers were used as crosslinkers to prepare three series of thermosensitive hydrogels with 2-(2-methoxyethoxy) ethyl methacrylate (MEMA). The effects of these crosslinkers on the hydrogel’s properties such as swelling behavior, mechanical properties, decomposability and thermoreversibility were investigated and compared with the hydrogel crosslinked by N,N′-bisacrylyl cystamine. The results showed that the equilibrium swelling ratio (SReq) of the hydrogel was affected by the hydrophilic group on the structure of the crosslinker and branch distribution of dendrimer crosslinker. More hydrophilic groups led to higher SReq; however, more complex branch distribution occupied the storage space of water and thus reduced the SReq. The prepared hydrogels all showed apparent thermoreversibility, and the critical gel transition temperature (CGTT) of these hydrogels increased with an increase of hydrophilic group in the crosslinker. Their CGTT showed a range from 26 °C (pure polymer) to 45 °C. More importantly, disulfide bonds in the synthesized hydrogel could be decomposed in the presence of cysteine. This result was confirmed by the change of swelling ratio and mechanical properties before and after they were treated with cysteine. The hydrogels decomposed by cysteine showed higher swelling ratio than the pristine hydrogels. And for mechanical properties, the shear modulus, Young’s modulus and effective crosslinking density of the decomposed hydrogels are lower than the pristine hydrogels. In summary, a thermoresponsive and cysteine-responsive hydrogel has been developed.

Thermoresponsive and Injectable Composite Hydrogels of Cellulose Nanocrystals and Pluronic F127.

Thermoresponsive amphiphilic Pluronic F127 triblock copolymer solutions have been widely investigated in smart biomaterial applications due to the proximity of its critical gel temperature to human body temperature. Meanwhile, cellulose nanocrystals (CNCs) have quickly become the focus of many drug delivery and tissue engineering applications due to their biocompatibility, abundance, ability to conjugate with drug molecules, and superior rheological properties. Herein, we investigate the phase behavior and thermo-rheological properties of the composite hydrogels containing cellulose nanocrystals (up to 5% by weight) and the temperature responsive Pluronic F127. Our results revealed an unprecedented role of CNC network formation on micellization and gelation behavior of the triblock copolymer. Linear and nonlinear rheological analysis suggest that at low and moderate nanocrystal loadings (1-3% by weight), the composite gel remarkably becomes softer and deformable compared to the neat Pluronic F127 gels. The softening effect results from the disruption of the close packed micelles by the rodlike CNCs. At high concentrations, however, the nanocrystals form their own network and the micelles are trapped within the CNC meshes. As a result, the original (neat F127) hard-gel modulus is recovered at 4 to 5% nanocrystal loading, yet the composite gel is much more deformable (and tougher) in the presence of the CNC network. Our temperature sweep experiments show that the CNC addition up to 3% does not change the rapid thermal gelation of the F127 solutions; therefore, these composites are suitable for smart drug delivery systems. On the other hand, at higher CNC concentrations, abrupt viscosity transition is not observed, rather the composite gels smoothly thicken with temperature in contrast to thermal thinning of the aqueous neat CNC. Thus, they can be used as smartly adaptive biolubricants and bioviscostatic materials.

Concentration Polarization Enabled Reactive Coating of Nanofiltration Membranes with Zwitterionic Hydrogel.

In this study, the bottleneck challenge of membrane fouling is addressed via establishing a scalable concentration polarization (CP) enabled and surface-selective hydrogel coating using zwitterionic cross-linkable macromolecules as building blocks. First, a novel methacrylate-based copolymer with sulfobetain and methacrylate side groups was prepared in a simple three-step synthesis. Polymer gelation initiated by a redox initiator system (ammonium persulfate and tetramethylethylenediamine) for radical cross-linking was studied in bulk in order to identify minimum (“critical”) concentrations to obtain a hydrogel. In situ reactive coating of a polyamide nanofiltration membrane was achieved via filtration of a mixture of the reactive compounds, utilizing CP to meet critical gelation conditions solely within the boundary layer. Because the feasibility was studied and demonstrated in dead-end filtration mode, the variable extent of CP was estimated in the frame of the film model, with an iterative calculation using experimental data as input. This allowed to discuss the influence of parameters such as solution composition or filtration rate on the actual polymer concentration and resulting hydrogel formation at the membrane surface. The zwitterionic hydrogel-coated membranes exhibited lower surface charge and higher flux during protein filtration, both compared to pristine membranes. Salt rejection was found to remain unchanged. Results further reveal that the hydrogel coating thickness and consequently the reduction in membrane permeance due to the coating can be tuned by variation of filtration time and polymer feed concentration, illustrating the novel modification method’s promising potential for scale-up to real applications.

Phenomenological model of viscoelasticity for systems undergoing sol–gel transition

A material undergoing sol–gel transition evolves from the pre-gel (sol) state to the post-gel state through the critical gel state. It is well-known that critical gels exhibit power-law rheology. The faster decay of the relaxation modulus in the pre-gel state can be empirically described by modifying this power-law decay with a stretched exponential factor. A phenomenological analytical expression for the relaxation modulus in the post-gel state is proposed by invoking the symmetry associated with the evolution of the relaxation time on either side of the critical gel state and by accounting for natural constraints. This expression, which depends on the extent of cross-linking, can be suitably transformed to obtain analytical expressions for the dynamic moduli and the continuous relaxation time spectrum. Thus, the proposed model facilitates a comprehensive description of viscoelastic evolution from the pre-gel to the post-gel states. It is validated by carrying out experiments on a model colloidal gel-forming system and by considering other diverse gel-forming systems studied in the literature. After calibrating the parameters of the phenomenological model, it is found to be in excellent agreement with experimental data. Such a well-calibrated phenomenological model can be used to determine any linear viscoelastic response over a wide range of frequencies and extents of cross-linking encompassing the entire sol–gel transition.