Gel Phase Transition Research Articles

Budesonide-hydroxypropyl-β-cyclodextrin inclusion complex in binary poloxamer 407/403 system for ulcerative colitis treatment: A physico-chemical study from micelles to hydrogels

Budesonide (BUD) is a glucocorticoid widely used for the treatment of ulcerative colitis. In this work, we propose the study of the system BUD-HP-β-CD inclusion complex incorporated into PL 407 and PL407-PL403 thermoreversible hydrogels, considering physico-chemical and pharmaceutical aspects. Complexation between BUD and HP-β-CD was confirmed by phase solubility studies (1:1 stoichiometry, Kc=8662.8M−1), DSC, FTIR and microscopy analyzes. BUD solubility in simulated upper and lower colon fluids was improved in a dependence of HP-β-CD and PL 407 or PL407-PL403 association. Micellar hydrodynamic diameter studies showed the interaction between HP-β-CD and PL blocks, as well as the reorganization of the micellar system in the presence of BUD and its inclusion complex. Micellization temperature (Tm) was not shifted, but sol–gel phase transition studies showed that in the presence of BUD, HP-β-CD or BUD:HP-β-CD complex, the association PL407-PL403 favored the gel formation close to the physiological temperature. Physico-chemical and in vitro release assays studies revealed no competitive displacement of BUD from the HP-β-CD cavity evoked by PL407 or PL407-PL403 addition. These findings point out the BUD-HP-β-CD in PL-based hydrogels as strategies for future investigations on development of new pharmaceutical formulations for the treatment of ulcerative colitis.

The stimuli-responsive multiphase behavior of core–shell nanogels with opposite charges and their potential application in in situ gelling system

Concentrated p(N-isopropylacrylamide) (PNIPAM) nanogel dispersions exhibited rich temperature-sensitive sol–gel phase transition behavior. In the present work, the influence of electrostatic forces between nanogel particles, including attraction and repulsion, on the sol–gel phase transition behavior of PNIPAM nanogel dispersions has been studied. Both oppositely charged nanogels with core–shell structures (NIA and PND nanogels) were synthesized, and their shell charges were calculated to −0.33 and 0.082mmol/g by potentiometric titration method. When mixed with various ratio of negative and positive charge (NC value), the resultant mixture dispersions of NIA and PND nanogel (OCNs) exhibited different aggregating behavior from NIA and PND nanogels. OCN-e aggregates (NC value=1/4), which exhibited temperature-independence of electric neutrality, had the maximum size, about 1.9–2.2 times larger than NIA or PND nanogels. Concentrated OCN-e dispersions exhibited stronger ability to form shrunken gel. Its CGC was about 2.0wt%, 4-times lower than that of NIA and PND nanogels (about 8.0wt%). In vitro and in vivo gelling results indicated that OCN-e aggregates could form free-standing gel with good mechanical strength, and were promising to be developed as new in situ gelling system.

Effect of milk fat content on the viscoelasticity of mozzarella-type cheese curds

The effect of fat content in cheese curds on their rheological properties was examined using dynamic shear measurements. Surplus fat addition to milk samples caused two distinct types of changes in the temperature dependence of the viscoelastic moduli of resultant curds. The first was a significant reduction in the moduli over a wide temperature range, which is attributed to the presence of liquefied fat globules within the milk protein network. The second was the excess contribution to the low-temperature moduli owing to the reinforcing effect of solidified fat globules. An upward shift in the sol–gel phase transition temperature driven by an increased fat content was also observed.

Volume phase transitions of cholesteric liquid crystalline gels.

We present a mean field theory to describe anisotropic deformations of a cholesteric elastomer without solvent molecules and a cholesteric liquid crystalline gel immersed in isotropic solvents at a thermal equilibrium state. Based on the neoclassical rubber theory of nematic elastomers, we derive an elastic energy and a twist distortion energy, which are important to determine the shape of a cholesteric elastomer (or gel). We demonstrate that when the elastic energy dominates in the free energy, the cholesteric elastomer causes a spontaneous compression in the pitch axis and elongates along the director on the plane perpendicular to the pitch axis. Our theory can qualitatively describe the experimental results of a cholesteric elastomer. We also predict the first-order volume phase transitions and anisotropic deformations of a gel at the cholesteric-isotropic phase transition temperature. Depending on a chirality of a gel, we find a prolate or oblate shape of cholesteric gels.

Dual Stimuli-Responsive Redox-Active Injectable Gel by Polyion Complex Based Flower Micelles for Biomedical Applications

We developed and evaluated a redox-active injectable gel (RIG) comprising poly[4-(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene]-b-poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene] (PMNT–PEG–PMNT) triblock copolymer and poly(acrylic acid) (PAAc). Cationic PMNT–PEG–PMNT and anionic PAAc formed polyion complexes (PIC) flower micelles without aggregation, which was confirmed by FRET analysis. We confirmed that the PIC flower micelles exhibited irreversible sol–gel phase transitions with increasing both temperatures and ionic strengths. The PIC flower micelles had a low viscosity at room temperature. The viscosity increased with increasing temperatures and ionic strengths, and the RIG was formed under physiological conditions. The RIG was able to provide sustained release of an anionic model drug for more than 4 weeks without an initial burst. These results indicated that the RIG has potential as an injectable system for pharmaceutical and biomedical applications such as a local delivery carrier for the controlled release of charged drugs such as proteins or siRNA.

Injectable and Biodegradable pH-Responsive Hydrogels for Localized and Sustained Treatment of Human Fibrosarcoma.

Injectable hydrogels are an important class of biomaterials, and they have been widely used for controlled drug release. This study evaluated an injectable hydrogel formed in situ system by the reaction of a polyethylene glycol derivative with α,β-polyaspartylhydrazide for local cancer chemotherapy. This pH-responsive hydrogel was used to realize a sol-gel phase transition, where the gel remained a free-flowing fluid before injection but spontaneously changed into a semisolid hydrogel just after administration. As indicated by scanning electron microscopy images, the hydrogel exhibited a porous three-dimensional microstructure. The prepared hydrogel was biocompatible and biodegradable and could be utilized as a pH-responsive vector for drug delivery. The therapeutic effect of the hydrogel loaded with doxorubicin (DOX) after intratumoral administration in mice with human fibrosarcoma was evaluated. The inhibition of tumor growth was more obvious in the group treated by the DOX-loaded hydrogel, compared to that treated with the free DOX solution. Hence, this hydrogel with good syringeability and high biodegradability, which focuses on local chemotherapy, may enhance the therapeutic effect on human fibrosarcoma.

Gelation by Novel Aprotic Low-molecular-mass Organic Gelators Based on a Gemini 4-[2-(Perfluorobutyl)ethylthio]phenoxy Unit

Abstract We found novel aprotic low-molecular-mass organic gelators (LMOGs) with simple molecular structure based on a gemini 4-[2-(perfluorobutyl)ethylthio]phenoxy unit. These aprotic LMOGs formed a physical gel with a thermally reversible sol–gel phase transition in a wide variety of alcoholic and polar solvents such as 1-octanol and propylene carbonate at concentrations below 1 wt %.

Rational design and application of a redox-active, photoresponsive, discrete metallogelator.

A photoresponsive discrete metallogelator was rationally designed by incorporating a photochromic azobenzene subunit in the structure of a redox-active ferrocene-peptide conjugate. The target molecule was purposefully equipped with a dipeptide unit capable of self-assembly in response to sonication. The designed molecule was shown to undergo supramolecular self-assembly and achieve organogelation in response to ultrasound, light, heat, and redox signals. The sol-gel phase transition of the designed gelator was found to be sensitive to a plethora of input stimuli, allowing the application of the sol-gel transition behavior in basic logic gate operations. A gel-based NOT logic gate operation was realized when the redox-active property of the organogel was examined by using different oxidizing agents. The smart response of the gelator was further exploited in designing XOR operations under oxidizing or non-oxidizing conditions.

Biodegradable and stimuli sensitive amphiphilic graft copolymers and their sol–gel phase transition behavior

pH and temperature‐sensitive biodegradable poly(β‐aminoester)‐graft‐poly(ε‐caprolactone)‐block‐methoxy poly(ethylene glycol) (PBAE‐g‐PCL‐b‐mPEG) amphiphilic graft copolymers with different molecular weights were synthesized. The structure of these copolymers was adjusted by varying the feed ratios of ε‐caprolactone to methoxy poly(ethylene glycol)s (mPEG), amine and diacrylate monomer amounts and the molecular weight of mPEG. Aqueous solutions of these copolymers formed micelles at lower concentrations; however, the concentrated solutions showed a reversible sol–gel transition property depending on both pH and temperature changes under representative physiological conditions (pH 7.4, 37°C). The effects of the molecular weight of pH‐sensitive poly(β‐aminoester) block and mPEG group, the hydrophobic to hydrophilic block ratio (PCL/mPEG) and the concentration of the copolymer on the sol–gel transition were investigated. Proton nuclear magnetic resonance (1H NMR) and gel permeation chromatography measurements were used to characterize the structure of the synthesized copolymers. The self‐assemble behavior and critical micelle concentration of the amphiphilic copolymers were estimated in phosphate buffer solution using fluorescence spectroscopy. The gelling behavior was measured by using tube inversion method. At pH 7.4, all copolymer solutions prepared 20 wt% concentration indicated sol–gel transition with increasing temperature. In vitro degradation experiments displayed that the synthesized graft copolymers mostly degraded hydrolytically within 20 days under physiological conditions. In order to investigate the potential application of synthesized hydrogels in drug delivery, Methylene Blue was used and approximately 70% of the loaded amount was released in 120 hr. The findings indicate that obtained graft copolymers can be used as injectable biodegradable carriers for pharmaceutical drugs. Copyright © 2015 John Wiley & Sons, Ltd.

The Tight Coupling and Non-Linear Relationship between the Macroscopic Electrical and Optical Concomitants of Electrochemical CNS Waves Reflect the Non-Linear Dynamics of Neural Glial Propagation

In isolated chick retina, the visualization of electrochemical self-organized patterns is possible due to the presence of macroscopic intrinsic optical signals (IOSs). Isolated circular waves, standing patterns, and self-sustained sequences of spirals are all easily obtained using an IOS approach. In this paper we present the tight coupling and non-linear relationship between optical and electrical wave concomitants, and potassium-induced whole tissue excitability changes. Elementary statistical methods and time series analyses were applied to two sets of data: 1) solitary circular retinal spreading depression waves, and 2) tissue response to exogenous potassium fast pulses. The results were interpreted from the point of view of non-linear thermodynamical concepts and volume phase transitions in polyanionic gels according to the Tasaki action potential model. From these and previous results, it is clear that the glial network and extracellular matrix contribute to the propagation and emergence of these patterns.

Non-invasive and continuous monitoring of the sol-gel phase transition of supramolecular gels using a fast (open-ended coaxial) microwave sensor.

An open coaxial re-entrant microwave sensor has been used for the non-invasive and continuous monitoring of the sol-gel transition of physical gels characterized by different gelation mechanisms, solvents, compositions, and stabilities. Comparison of measurements by differential scanning calorimetry allowed the identification of the phase transition by a change in the dielectric properties of the material over time.

A glucosyl triblock copolymer: synthesis and its injectable thermo- and pH-responsive behaviours

A new glucosyl triblock PGNA copolymer was first synthesized and the aqueous PGNA copolymer solution exhibits good sol–gel phase transition behaviours. The formed hydrogels are sensitive to the temperature and pH.

Investigating Lipid Phase Changes from Liquid Crystalline to Ripple to Gel Phases with All-Atom Molecular Dynamics Simulations

Lipid mixed with water can exist in many different phases that depends on various factors, such as hydration, temperature and pressure (J. Chem. Theory Comput.,6 (8): 2488 (2010)). The liquid crystalline (chain-disordered state) is a well-studied phase for single lipid bilayers both experimentally and computationally. At low enough temperatures or hydration levels, this chain-disordered state can change to a gel state with high chain order and a certain chain tilt with respect to the membrane normal. Depending on the lipid, an intermediate phase can exist between the gel and liquid crystalline phase, which is known as the ripple phase. The main objective of this study was probing the accuracy of the CHARMM36 (C36) force field (FF) (J. Phys. Chem. B.,114 (23): 7830 (2010)) in predicting phase changes in lipid bilayers. Pure and mixed lipid bilayers at different compositions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) were studied using molecular dynamics (MD) simulations. Based on the pure gel-phase transition temperature of each lipid, a range of temperatures was selected (from 200C to 400C) (Biochem. 18: 3280 (1979)). MD simulations were able to capture ripple phase in %25 DMPC and %75 DPPC mixture and pure DMPC at 250C. Simulations were run for 200-300 ns. MD simulations also show either a gel state or gel-like state depending on if the system gets trapped (gel-like is a state without proper leaflet alignment). Phase diagram was compared to that obtained from experimental data such as NMR. Based on the phase diagram and our transition temperatures, C36 FF accurately predicts the phase transitions of this fully saturated PC lipids. Therefore, studies on phase coexistence of liquid ordered and liquid disordered domains are likely to be accurate using the C36 FF.

Novel Tri-Cholesteryl Derivatives-Based Low Molecular Mass Organic Gelators with Multi-Stimuli Responsive Properties

Two novel tri-cholesteryl derivatives 1 and 2 have been designed and prepared. Gelation tests in 30 liquids revealed that 1 is a more efficient gelator than 2. Interestingly, the gel of 1/cyclohexane shows a reversible sol–gel phase transition in response to a variety of disparate stimuli such as temperature, stress, and HCl gas. In particular, a fully reversible thixotropic property was observed, which has been rarely reported before. Fourier transform infrared spectroscopy and 1H NMR measurements revealed that hydrogen bonding is an important driving force for the formation of the gel networks. The network structures of 1 and 2 in their cyclohexane gels were studied by scanning electron microscopy and X-ray diffraction analyses, and possible packing models were proposed accordingly. The findings demonstrated in the present work suggest that there is a big potential for developing tri-cholesteryl derivatives into extraordinary low molecular mass gelators.

Thermoresponsive Reversible Phase-transition of Alginate-based Semi-IPN Gel through Self-assembly of Interpenetrated Elastin-like Polypeptide

Abstract We describe, for the first time, a simple and one-pot fabrication of biocompatible hydrogels functioning as an elastin-like polypeptide (ELP) matrix in terms of thermoresponsibility and structure-proved bioavailability, without complicated pretreatment and synthesis. For this purpose, composite hydrogels were formed with a semi-IPN structure wherein untreated ELPs interpenetrated the alginate–Ca2+ hydrogel as the host three-dimensional network. These biocompatible and stimuli-responsive materials are highly useful as a novel injectable matrix to induce tissue differentiation after cellular encapsulation.

Gelation of PAAm-PVP composites: A fluorescence study

Hybrid hydrogels are a new class of composite materials. Polyacrylamide (PAAm) hydrogels are mainly produced by free radical crosslinking copolymerization (FCC) of AAm in the presence of N, N′-methylene bis (acrylamide) (BIS) as the crosslinker. Pyranine doped PAAm-poly (N-vinyl pyrrolidone) (PVP) composite were prepared with different amounts of PVP varying in the range between 0.0015 and 0.1 gr. It was observed that pyranine molecules as a fluoroprobe bind to AAm and PVP chains upon the initiation of the polymerization, causing the fluorescence spectra of the bonded pyranines shift to the shorter wavelengths. The sol–gel phase transition and its universality were monitored and tested as a function of PVP contents. Observations around the critical point show that the gel fraction exponent, β, agreed with the percolation result for below 0.025 gr PVP contents. However, classical result was observed above 0.0125 gr PVP content.

Solvent‐Modulated Self‐Assembly of C3‐Symmetric Tris‐Urea into a Discrete Dimer and Supramolecular Gel

AbstractA C3‐Symmetric tris‐urea derivative self‐assembles into either a discrete dimer or a supramolecular gel via continuous assembly, depending on the solvent used. In the less polar CDCl3, the discrete dimer was selectively formed, whereas in the more polar acetonitrile and acetone, a supramolecular gel was obtained. Additionally, the gel‐sol phase transition of an acetonitrile gel of the tris‐urea derivative responds bidirectionally to chemical stimuli.

Avidity-controlled hydrogels for injectable co-delivery of induced pluripotent stem cell-derived endothelial cells and growth factors

To translate recent advances in induced pluripotent stem cell biology to clinical regenerative medicine therapies, new strategies to control the co-delivery of cells and growth factors are needed. Building on our previous work designing Mixing-Induced Two-Component Hydrogels (MITCHs) from engineered proteins, here we develop protein–polyethylene glycol (PEG) hybrid hydrogels, MITCH-PEG, which form physical gels upon mixing for cell and growth factor co-delivery. MITCH-PEG is a mixture of C7, which is a linear, engineered protein containing seven repeats of the CC43 WW peptide domain (C), and 8-arm star-shaped PEG conjugated with either one or two repeats of a proline-rich peptide to each arm (P1 or P2, respectively). Both 20kDa and 40kDa star-shaped PEG variants were investigated, and all four PEG-peptide variants were able to undergo a sol–gel phase transition when mixed with the linear C7 protein at constant physiological conditions due to noncovalent hetero-dimerization between the C and P domains. Due to the dynamic nature of the C–P physical crosslinks, all four gels were observed to be reversibly shear-thinning and self-healing. The P2 variants exhibited higher storage moduli than the P1 variants, demonstrating the ability to tune the hydrogel bulk properties through a biomimetic peptide-avidity strategy. The 20kDa PEG variants exhibited slower release of encapsulated vascular endothelial growth factor (VEGF), due to a decrease in hydrogel mesh size relative to the 40kDa variants. Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) adopted a well-spread morphology within three-dimensional MITCH-PEG cultures, and MITCH-PEG provided significant protection from cell damage during ejection through a fine-gauge syringe needle. In a mouse hindlimb ischemia model of peripheral arterial disease, MITCH-PEG co-delivery of hiPSC-ECs and VEGF was found to reduce inflammation and promote muscle tissue regeneration compared to a saline control.

Physical properties of aqueous mixtures of the ionic 1-ethl-3-methyl imidazolium octyl sulfate: A new ionic rigid gel

We report the existence of hydrophobically driven lyotropic rigid gel phase in aqueous mixtures of the ionic liquid (IL) 1-ethyl-3-methyl imidazolium octyl sulfate (EMIM-OS), and we characterize the physical properties of the gel phase by means of density, electrical conductivity and viscosity measurements. Also we include polarized microscopy images, showing the existence of a crystalline-like gel phase with the cations and anions (mainly the alkyl chain of this last ones) ordered in a fashion similar to a liquid crystal, which is induced by the presence of the water molecules. As was pointed out briefly in a previous paper, some of the mixtures of that system under goes a (liquid+gel) phase transition only in a quite narrow concentration interval: for ionic liquid molar fraction, xIL, from 0.09 to 0.5. Below xIL=0.09 and above xIL=0.5, the mixtures crystallize at low temperature becoming a hard solid crystal. Here we report the complete phase diagram of this binary system, as well as measurements of the temperature behavior of several physical properties around the (liquid+gel) and (liquid+crystal) transitions. Curiously enough, we did not detect any change in the temperature dependence of the measured magnitudes at the (liquid+gel) phase transition, but for viscosity, even in the case of the electrical conductivity. Viscosity increases enormously at the transition going from less than 0.3Pa·s three degrees above the liquid to gel transition temperature to more than 20Pa·s three degrees below it, indicating a deep change in the mass transport in the system as molecular diffusion is frozen out. No similar change is registered in the charge transport mechanism nor in density from liquid to gel phases in agreement with previous theoretical predictions of pseudolattice structure of ILs in their liquid phase.

Thermosensitive in situ hydrogel based on the hybrid of hyaluronic acid and modified PCL/PEG triblock copolymer

In this work, a new hydrogel was constructed using poly(ɛ-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)–poly(ethylene glycol)–poly(ɛ-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) tri-block copolymers (PECT) with hyaluronic acid (HA) in order to expand application scopes of PECT hydrogel. The rheological and sol–gel phase transition behaviors were investigated by rheometer and test tube inversion method, and the interior morphologies of hydrogel systems were observed by scanning electron microscope (SEM). With the introduction of HA, certain properties of PECT hydrogel, such as viscosity and morphology, have present trends with regularity. Furthermore, with the participation of HA, the degradation and release of acetylsalicylic acid was slightly affected, however, the drug release mechanism of hydrogel has not been changed. PECT/HA hydrogel is confirmed to be non-toxic through a test to NIH3T3 cells. In conclusion, blending with HA is a feasible and safe method to tune properties of PECT hydrogel.