Critical Gelation Temperature Research Articles

Preparation and characterization of poly(ϵ-caprolactone-co-p-dioxanone)-poly(ethylene glycol)-poly(ϵ-caprolactone-co-p-dioxanone)/bioactive inorganic particle nanocomposites

With an aim to develop injectable hydrogel with improved solution stability and enhanced bone repair function, thermogelling poly(e-caprolactone-co-p-dioxanone)-poly(ethylene glycol)-poly(e-caprolactone–co-p-dioxanone) (PECP)/bioactive inorganic particle nanocomposites were successfully prepared by blending the triblock copolymer (PECP) with nano-hydroxyapatite (n-HA) or nano-calcium carbonate (n-CaCO3). The hydrogel nanocomposites underwent clear sol–gel transitions with increasing temperature from 0 to 50°C. The obtained hydrogel nanocomposites were investigated by 1H NMR, FT-IR, TEM, and DSC. It was found that the incorporation of inorganic nanoparticles into PECP matrix would lead to the critical gelation temperature (CGT) shifting to lower values compared with the pure PECP hydrogel. The CGT of the hydrogel nanocomposites could be effectively controlled by adjusting PECP concentration or the content of inorganic nanoparticles. The SEM results showed that the interconnected porous structures of hydrogel nanocomposites were potentially useful as injectable scaffolds. In addition, due to the relatively low crystallinity of PECP triblock copolymer, the aqueous solutions of the nanocomposites could be stored at low temperature (5°C) without crystallization for several days, which would facilitate the practical applications. The PECP/bioactive inorganic particle hydrogel nanocomposites are expected to be promising injectable tissue engineering materials for bone repair applications. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Temperature-induced phase-transitions of methoxyoligo(oxyethylene) styrene-based block copolymers in aqueous solution

Novel well-defined diblock copolymers based upon styrene substituted with pendant methoxyoligo(oxyethylene) groups (4-CH3O(EO)4St, TrEGS) were prepared by sequential atom transfer radical polymerization. Polystyrene (PS) was synthesized as the first block in the copolymer using (1-bromoethyl)benzene as the initiator. This was followed by growth of a second block composed of PTrEGS. Each copolymer exhibits a lower critical solution temperature (LCST) in aqueous solution, and the LCST depends on the length of the PTrEGS block and the copolymer composition. Longer PTrEGS chains result in higher LCST values in aqueous solutions. The cloud points (Tcs) of PS-b-PTrEGS copolymers are lower than that of PTrEGS homopolymer as determined by UV-visible spectroscopy. Variable-temperature NMR spectra show that the intensity of proton signals from oxyethylene groups dramatically decreases at temperatures above the cloud point, indicating phase transition due to hydrogen bonding changes. Dynamic light scattering (DLS) measurements indicate that micelles are formed, where the PS backbone serves as the core at 25 °C. Each of these block copolymer solutions transformed from transparent bluish solutions to white gels above certain concentrations (≥10 wt%) and temperatures (lower critical gelation temperature, LCGT). The gelation process is thermally reversible, implying physical crosslinking through hydrophobic interactions.

ABC Triblock Terpolymers Exhibiting Both Temperature- and pH-Sensitive Micellar Aggregation and Gelation in Aqueous Solution

Two poly(ethylene-alt-propylene)-b-poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-acrylic acid) (PEP-PEO-P(NIPAm-co-AA)) triblock terpolymers were synthesized by a combination of anionic and RAFT polymerizations, followed by acid hydrolysis. Micellar aggregation and gelation behavior in aqueous solutions were studied by dynamic light scattering (DLS) and rheology, respectively. DLS measurements on dilute solutions revealed that the triblock terpolymers form micelles with PEP cores and PEO-P(NIPAm-co-AA) coronae at room temperature and undergo a micelle to micellar aggregate transition upon heating. Rheological measurements showed that micellar aggregation manifests itself as gelation at higher concentrations (~4 wt %). The observed thermoresponsive aggregation and gelation is due to the intermicellar association of P(NIPAm-co-AA) blocks in the coronae above the lower critical solution temperature of the P(NIPAm-co-AA) block. The critical micellar aggregation and gelation temperatures are controlled by the mole fraction and degree of acrylic acid (AA) ionization in the P(NIPAm-co-AA) block, and therefore they can be modulated as functions of both pH and AA content in the polymer.

Temperature-sensitive star-shaped block copolymers hydrogels for an injection application: phase transition behavior and biocompatibility

A series of star-shaped poly(D,L-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (PLGA-mPEG) block copolymers with varying PLGA/mPEG block weight ratios, mPEG block length, and arm numbers were synthesized and phase transition behaviors were investigated. Phase transition characteristics, such as critical gel concentration (CGC) and critical gel temperature (CGT), were closely related to the molecular structure of the star-shaped block copolymers. The CGC was mainly determined by the balance of hydrophobic PLGA and hydrophilic mPEG block (PLGA/mPEG block ratio). The CGTs showed a stronger dependence on mPEG block length and arm number. Also, the CGTs can be adjusted by adding mPEG homopolymer additives. The weight fraction of mPEG had a stronger influence on the CGT values than molecular weight of mPEG. In addition, the MTT assay and histological observations confirmed the acceptable biocompatibility of the star-shaped block copolymer. Hence, the star-shaped PLGA-mPEG block copolymer was a promising candidate as a novel injectable gel.

Decisive Role of Hydrophobic Side Groups of Polypeptides in Thermosensitive Gelation

Thermosensitive hydrogels based on PEG and poly(l-glutamate)s bearing different hydrophobic side groups were separately synthesized by the ring-opening polymerization (ROP) of l-glutamate N-carboxyanhydrides containing different alkyl protected groups, that is, methyl, ethyl, n-propyl, and n-butyl, using mPEG(45)-NH(2) as macroinitiator. The resulting copolymers underwent sol-gel transitions in response to temperature change. Interestingly, the polypeptides containing methyl and ethyl showed significantly lower critical gelation temperatures (CGTs) than those bearing n-propyl and butyl side groups. Based on the analysis of (13)C NMR spectra, DLS, circular dichroism spectra, and ATR-FTIR spectra, the sol-gel transition mechanism was attributed to the dehydration of poly(ethylene glycol) and the increase of β-sheet conformation content in the polypeptides. The in vivo gelation test indicated that the copolymer solution (6.0 wt %) immediately changed to a gel after subcutaneous injection into rats. The mass loss of the hydrogel in vitro was accelerated in the presence of proteinase K, and the MTT assay revealed that the block copolymers exhibited no detectable cytotoxicity. The present work revealed that subtle variation in the length of a hydrophobic side group displayed the decisive effect on the gelation behavior of the polypeptides. In addition, the thermosensitive hydrogels could be promising materials for biomedical applications due to their good biocompatibility, biodegradability, and the fast in situ gelation behavior.

Rheological studies of thermo-responsive diblock copolymer worm gels

A series of diblock copolymer worms are prepared via aqueous dispersion polymerization using reversible addition–fragmentation chain transfer (RAFT) polymerization chemistry. More specifically, a poly(glycerol monomethacrylate) (PGMA) RAFT chain transfer agent is used to polymerize a water-miscible monomer, 2-hydroxypropyl methacrylate, at 70 °C. The poly(2-hydroxypropyl methacrylate) (PHPMA) chains become increasingly hydrophobic as they grow, which leads to nanoparticle formation. Careful control of the diblock composition is achieved by fixing the mean degree of polymerization (DP) of the PGMA stabilizer block at 54 and systematically varying the DP of the core-forming PHPMA block. This strategy enables the worm phase space to be targeted reproducibly. These worms form soft free-standing gels in aqueous solution due to inter-worm entanglements. Rheological studies enable the influence of the diblock copolymer composition on the gel strength, critical gelation concentration (CGC) and critical gelation temperature (CGT) to be assessed. A maximum in gel strength is observed as the DP of the PHPMA block is increased from 130 to 170. The initial increase is due to longer worms, while the subsequent decrease is associated with worm clustering, which leads to more brittle gels. The gel strength is reduced from approximately 100 Pa to 10 Pa as the copolymer concentration is lowered from 10 to 5 w/w%, with a CGC being observed at around 3 to 4 w/w%. The CGT is relatively concentration-independent, but sensitive to the diblock copolymer composition: longer (more PHPMA-rich) chains lead to the CGT being reduced from 20 °C to 7 °C. This is because longer PHPMA blocks require a greater degree of hydration to induce the worm-to-sphere transition, which can only achieved at progressively lower temperatures. Reversible de-gelation also occurs on cooling, since there can be no entanglements between isotropic particles. This RAFT formulation also provides a rare example of thermo-responsive diblock copolymer worms.

Effect of polymer molecular weight on the structural properties of non aqueous ethyl cellulose gels intended for topical drug delivery

Abstract The structural properties of five ethyl cellulose polymers (EC) in mixture with the non aqueous solvent of propylene glycol dicaprylate (PGD) have been investigated with a view to facilitating topical drug delivery. Total concentration of the polymer varied from 12 to 20% (w/w) and its weight average molecular weight was in the range of 64–223 kDa. Experimental techniques utilised were small-deformation dynamic oscillation in shear, attenuated total reflectance Fourier transform infrared spectroscopy (ATR FTIR) and wide-angle X-ray diffraction. The nature of the time and temperature dependence on viscoelastic functions of all samples could be treated with the Chambon and Winter criterion allowing determination of the critical gelation temperature in relation to polymer concentration and molecular weight. A further refinement of this school of thought allowed correlation between the viscoelastic relaxation exponent and fractal dimensions in thermally treated EC/PGD matrices. Tangible evidence on the packing arrangements of the ethyl cellulose network and the molecular nature of its interaction with the non aqueous solvent as a function of polymer concentration and molecular weight was provided by X-ray diffraction and infrared studies.

Synthesis and Characterization of a Multi‐Sensitive Crosslinked Injectable Hydrogel Based on Pluronic

This paper reports the construction of a novel multi-sensitive chemically crosslinked injectable hydrogel with strong mechanical strength by modifying Pluronic F127 responsive against temperature, pH and redox potential. Crosslinked polymer between benzaldehyde grafted Pluronic (P-A) and amine end capped Pluronic having disulfide linkage (P-B) have been synthesized and characterized with 1H NMR spectroscopy and GPC. The hydrogel under physiological conditions significantly altered sol-gel transition behaviors with much lower critical gelation concentrations and temperatures, compared to Pluronic hydrogels. The rheological characterization demonstrated that the moduli of the hydrogels were able to be tuned depending on molecular weight as well as pH, redox and temperature conditions.

Chitosan in situ gelation for improved drug loading and retention in poloxamer 407 gels

A method for the in situ gelation of poloxamers and the mucoadhesive polymer chitosan has been developed by exploiting the tendency of poloxamer solution to form gel at physiological temperatures and of chitosan (CT) to form ionotropic gel structures in the presence of sodium tripolyphosphate (TPP). Novel poloxamer gels containing CT–TPP complex formed in situ during the administration were prepared by mixing poloxamer–CT and poloxamer–TPP solutions in double syringes. The micellization and gelation of poloxamer 407 in the presence of chitosan and/or TPP were studied using differential scanning calorimetry and tube inversion; both additives were found to reduce the critical micellization temperature and critical gelation temperature of poloxamer aqueous solution. The poloxamer gels containing CT–TPP complex formed in situ were found to exhibit reduced dissolution rate and superior release characteristics with three different drugs – metoprolol, doxycycline and flufenamic acid. Furthermore, by varying the compositions of the two solutions independently, it is possible to control the pH in a way to suit the solubilization of a drug as well as the specific environment of a particular application site. By varying the concentrations of chitosan, TPP and poloxamer, the delivery system can be fine-tuned to afford gels with specific properties, ranging from nanoparticle suspensions to semisolid gels. These in situ gels have the potential to increase the utility of thermo-reversible poloxamers in drug delivery.

Thermogelling of Double Hydrophilic Multiblock and Triblock Copolymers of N,N-Dimethylacrylamide and N-Isopropylacrylamide: Chain Architectural and Hofmeister Effects

A series of thermoresponsive double hydrophilic (AB)(n) multiblock and ABA triblock copolymers of N,N-dimethylacrylamide (DMA) and N-isopropylacrylamide (NIPAM) with varying sequence lengths were synthesized via successive reversible addition-fragmentation chain transfer (RAFT) polymerizations by employing polytrithiocarbonate as the chain transfer agent. Previously, we reported that multiblock copolymers in dilute aqueous solutions can form either unimolecular or multimolecular micelles at elevated temperatures depending on the relative chain lengths of PDMA and PNIPAM sequences (Zhou et al. Langmuir 2007, 23, 13076-13084). In this follow-up work, we further explored and compared the chain architectural (multiblock vs triblock) and Hofmeister effects (addition of various sodium salts) on the gelation behavior of multiblock and ABA triblock copolymers at high concentrations and attempted to establish a correlation between the aggregation behavior and gelation properties of multiblock copolymers at low and high polymer concentrations, respectively. It was found that only m-PDMA(p)-PNIPAM(q) multiblock copolymers with PDMA and PNIPAM sequence lengths located within a specific range can form physical gels at elevated temperatures. Rheology measurements revealed that multiblock copolymers possess considerably lower critical gelation temperatures (CGT) and higher gel storage modulus, G'(gel), as compared to those of PNIPAM-b-PDMA-b-PNIPAM triblock copolymers possessing comparable sequence lengths. The addition of inorganic sodium salts can effectively facilitate thermogelling for multiblock and triblock copolymers, resulting in decreasing CGTs and critical gelation concentrations (CGCs) in the order of Hofmeister series with increasing hydration capabilities. The unique thermogelling behavior of aqueous multiblock copolymer solutions in the absence and presence of inorganic salts, as compared to that of ABA triblock copolymers, augurs well for their potential applications in various fields such as biomaterials and biomedicines.

Uniaxial elongational behavior of poly(vinyl chloride) physical gel

A poly(vinyl chloride) \((\mbox{PVC,}\;{\rm M}_{\rm w} =102\times 10^3)\) di-octyl phthalate (DOP) gel with PVC content of 20 wt.% was prepared by a solvent evaporation method. The dynamic viscoelsticity and elongational viscosity of the PVC/DOP gel were measured at various temperatures. The gel exhibited a typical sol–gel transition behavior with elevating temperature. The critical gel temperature (Tgel) characterized with a power–law relationship between the storage and loss moduli, G′ and G″, and frequency ω, \({G}^\prime={G}^{\prime\prime}{\rm /tan}\;\left( {{n}\pi {\rm /2}} \right)\propto \omega ^{n}\), was observed to be 152°C. The elongational viscosity of the gel was measured below the Tgel. The gel exhibited strong strain hardening. Elongational viscosity against strain plot was independent of strain rate. This finding is different from the elongational viscosity behavior of linear polymer solutions and melts. The stress–strain relations were expressed by the neo-Hookean model at high temperature (135°C) near the Tgel. However, the stress–strain curves were deviated from the neo-Hookean model at smaller strain with decreasing temperature. These results indicated that this physical gel behaves as the neo-Hookean model at low cross-linking point, and is deviated from the neo-Hookean model with increasing of the PVC crystallites worked as the cross-linking junctions.

Gel formation of mixtures of κ-carrageenan and sodium caseinate

Gelation of sodium κ-carrageenan (KC) in the presence of sodium caseinate (SC) was investigated by oscillating shear rheology. The effect of adding NaCl and KCl was investigated. Temperature ramps showed that SC had no influence on the critical gelation temperature, but increased the melting temperature when that of the pure gels was less than about 30 °C. The presence of SC also increased the gel strength of weak KC gels. Light scattering and confocal laser scanning microscopy showed that the proteins associated with the KC network. The rheology of the gels indicated that the mixed gels contained bonds involving both SC and KC in addition to pure KC bonds. At relatively high SC content the former type of bonds dominated.

Effect of DMSO on micellization, gelation and drug release profile of Poloxamer 407

The application of many recently developed or approved drugs and pharmaceuticals is seriously hampered by their low solubility in aqueous media. Hence, numerous promising pharmaceutical delivery systems (including novel “smart” systems based on poloxamer gels, which have highly advantageous thermo-reversible characteristics and low toxicity) cannot solubilize required doses of various drugs without additives such as co-solvents or salts. Therefore, we have studied the effects of dimethyl sulphoxide (DMSO) – a commonly used co-solvent during drug development stages – on the micellization, gelation and dissolution properties of aqueous poloxamer solutions. Differential scanning calorimetry and tube inversion experiments clearly showed that DMSO induces reductions in the critical micellization and gelation temperatures of poloxamer systems. In addition, high resolution solid state 1H Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) analyses provided indications of the specific chemical groups in the poloxamer affected by DMSO, and the molecular mechanism involved. The presence of DMSO accelerated dissolution of the pure gel in water and the release of a hydrophobic drug (flufenamic acid) from poloxamer gel, while it reduced the release of a hydrophilic drug (metoprolol tartrate).

Rheology of SiO2/(acrylic polymer/epoxy) suspensions. I. Linear viscoelasticity

Linear viscoelastic properties of SiO2/(AP/EP) suspension with various SiO2 volume fractions (ϕ) in a blend of acrylic polymer (AP) and epoxy (EP) were investigated at various temperatures (T). The AP/EP contained 70 vol.% of EP. The SiO2 particles were treated with epoxy silane coupling agent. The effects of the SiO2 particles are more pronounced in the terminal zone: a transition from viscoelastic liquid (ϕ ≤ 30 vol.%) to viscoelastic solid (ϕ ≥ 40 vol.%) was observed which can be interpreted as a critical gelation occurring at a critical particle content and critical gel temperature. The SiO2/(AP/EP) systems exhibited a critical gel behavior at ϕ ≅ 35 vol.% and T ≅ 100°C characterized with a power–law relationship between the storage and loss moduli (G ′ and G ″) and frequency (ω); G ′ = G ″/tan(nπ/2) ∝ ω n . The critical gel exponent (n) was estimated to be about 0.45. The gelation occurred with increasing T.

Frequency- and Temperature-Dependent Rheological Properties of an Amphiphilic Block Co-polymer in Water and Including Cell-Culture Media

This paper examines the effects of cell-culture media on the rheological properties of Pluronic F127, an amphiphilic triblock co-polymer of poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO). In an aqueous environment, F127 exhibits a reversible sol–gel transition upon an increase of temperature and has found wide applications as an injectable biomaterial. In contrast to most of the present polymer-physics studies of hydrogels in water, we examined its rheological properties in Dulbecco's Modified Eagle Medium (DMEM), DMEM with calf serum and phosphate-buffered saline (PBS) solution, compared with those in deionized water. The critical gelation temperatures (T gel) were found to be lowered as compared to that in pure water. The differences among the three experimental groups were relatively less significant. The zero viscosity η 0 of sols and equilibrium modulus G e of gels were enhanced at a given temperature, but they kept universal values under a given temperature difference, T – T gel. The basic frequency-related scaling characteristics of a typical percolated network, G′ ∼ ωn and G′′ ∼ ωn , remained in Pluronic hydrogels at the gel points. Two power laws, η 0 ∼ ((T gel – T)/T gel)–s and G e ∼ ((T – T gel)/T gel) m described well the sols and gels near T gel, respectively. All the four systems exhibited similar critical scaling exponents. As a result, our studies illustrate that the changes of transition points and rheological properties of Pluronic hydrogels in cell-culture media should be taken into consideration but are not awfully large.

Molecular weight effects on gelation and rheological properties of konjac glucomannan–xanthan mixtures

AbstractFractions of konjac glucomannan (KGM) with various viscosity‐average molecular weights (Mv) ranging from 4.00 × 105 to 2.50 × 106 were prepared by hydrolysis degradation in hydrochloride acid/ethanol. Effect of Mv of KGM on the critical gelation temperature (Tgel) determined by Winter–Chambon criterion and the elasticity of KGM/xanthan mixed gels, a kind of binary gel formed by synergistic gelation, were investigated by dynamic viscoelastic measurements. It was shown that the value of Tgel of the gel was shifted to a higher temperature and the gel strength was enhanced when Mv of KGM was increased. The critical Mv (1.91 × 106) was observed, above which the Tgel and elasticity of the mixed gels showed no or slight increase. It was suggested that Tgel and elasticity of KGM/xanthan mixed gels mainly depend on the structure of junction zones driven by the strong interaction between KGM and xanthan, which was gradually improved with increasing Mv of KGM. It was found that the critical strain and yield stress of the mixed gels increased monotonically with the increasing Mv of KGM. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 313–321, 2010

Influences of nonsolvent and temperature on critical viscoelastic behaviors of ternary polyacrylonitrile solutions around the sol‐gel threshold

AbstractViscoelastic experiments were performed to study the influence of nonsolvent and temperature on critical viscoelastic behaviors of ternary polyacrylonitrile (PAN) solutions around the sol‐gel threshold. The dynamic critical parameters around the sol‐gel threshold were determined using dynamic rheometer. The sol‐gel transition takes place at a critical gel temperature at which the scaling law of G′(ω) ∼ G″(ω) ∝ ωn holds, allowing an accurate determination of the critical gel temperature by means of the frequency independence of the loss tangent. Although the gel points of PAN solutions increase with increasing H2O content, the results show that the scaling exponent n at the gel point is found to be universal for all ternary PAN solutions, which is independent of temperature and H2O content, indicating the similarity of the fractal structure in the critical PAN gels. The gelation of ternary PAN solutions induced by adding a nonsolvent and by decreasing the temperature is demonstrated to be a thermoreversible process, which implies that the PAN gels are physical gels. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2637–2643, 2008

Rheological behavior during thermotropic gelation of polyacrylonitrile concentrated solutions

Dynamic viscoelastic properties of polyacrylonitrile(PAN)/DMSO/H2O solutions with different H2O contents were studied as a function of temperature. These PAN solutions gradually became gel with decreasing temperature. The sol-gel transition took place at a critical gel temperature, at which the scaling law of G′(ω)∼G″(ω)∝ωn held, allowing an accurate determination of the critical gel temperature by means of the frequency independence of the loss tangent. The gel point of PAN solutions increases with increasing H2O content. The scaling exponent n (=0.86) at the gel point is confirmed to be universal for PAN gels, which is independent of temperature, suggesting the similarity of the fractal structure in the critical PAN gels.

Biocompatible Wound Dressings Based on Chemically Degradable Triblock Copolymer Hydrogels

The synthesis of a series of thermo-responsive ABA triblock copolymers in which the outer A blocks comprise poly(2-hydroxypropyl methacrylate) and the central B block is poly(2-(methacryloyloxy)ethyl phosphorylcholine) is achieved using atom transfer radical polymerization. These novel triblock copolymers form thermo-reversible physical gels with critical gelation temperatures and mechanical properties that are highly dependent on the copolymer composition and concentration. TEM studies on dried dilute copolymer solutions indicate the presence of colloidal aggregates, which is consistent with micellar gel structures. This hypothesis is consistent with the observation that incorporating a central disulfide bond within the B block leads to thermo-responsive gels that can be efficiently degraded using mild reductants such as dithiothreitol (DTT) over time scales of minutes at 37 degrees C. Moreover, the rate of gel dissolution increases at higher DTT/disulfide molar ratios. Finally, these copolymer gels are shown to be highly biocompatible. Only a modest reduction in proliferation was observed for monolayers of primary human dermal fibroblasts, with no evidence for cytotoxicity. Moreover, when placed directly on 3D tissue-engineered skin, these gels had no significant effect on cell viability. Thus, we suggest that these thermo-responsive biodegradable copolymer gels may have potential applications as wound dressings.

Gelation of konjac glucomannan crosslinked by organic borate

A series of thermoreversible konjac glucomannan gels crosslinked by organic borate were prepared. The gel network was formed through the crosslinking reaction between borate ions dissociated from organic borate and the cis-diol hydroxyl groups on the mannose units of polysaccharide chains. The rheological properties of the complex gels were studied by dynamic viscoelastic measurement. The gelation kinetics of the gels were studied and the critical gelation points of the gels were exactly determined by the Winter–Chambon criterion. The effects of temperature and composite ratio on the shear storage modulus ( G ′), the loss modulus ( G ″), and the sol-gel transition points were investigated. The critical gel-sol temperatures of the complex gels were successfully elucidated by Winter–Chambon criterion. The effect of crosslinking density on the critical gelation temperature and the elasticity of the gels were discussed.