Volume Phase Transition Temperature Research Articles

Correlating the effect of co-monomer content with responsiveness and interfacial activity of soft particles with stability of corresponding smart emulsions

HypothesisThis study presents the synthesis and characterization of Poly(N-isopropylacrylamide)-co-methacrylic acid (PNIPAM-co-MAA) based multi-responsive soft microgel particles employed as “smart emulsifiers” for controlled stabilization and breakage of the decane-in-water Pickering emulsions. These soft microgel particles can act as reversible stabilizers, i.e. they can either stay at the oil-water interface by supporting emulsion formation or preventing aggregates; while triggering demulsification can be controlled by varying the temperature, pH or ionic strength of the microgel system. ExperimentsDynamic light scattering was applied to observe the variation in hydrodynamic radius of the particles as a function of temperature and pH of the multi-responsive microgel system. Microgel composition was varied in terms of MAA-content and influence of this variation on their thermo-sensitivity and pH responsiveness as well as on the stability of corresponding emulsions was evaluated. FindingsThe microgel particles with highest MAA content showed a significant impact on multi-responsive behaviour. Thermal sensitivity is pH dependent under acidic conditions but this dependence is gradually reduced as the pH increases above 7.5. On the other hand, pH-responsiveness is enhanced with the rise in temperature and stable emulsions were formed under highly alkaline conditions even the temperature was far above the volume phase transition temperature (VPTT). Understanding the correlation of stimuli responsiveness at interface with the emulsion stability would help to fabricate and design novel smart Pickering emulsions with better control over desired properties.

POSS Hybrid Robust Biomass IPN Hydrogels with Temperature Responsiveness.

In order to improve the performance of traditional sodium alginate (SA) hydrogels cross-linked by Ca2+ ions to meet greater application demand, a strategy was designed to structure novel SA-based gels (named OP-PN gels) to achieve both stimulus responsiveness and improved mechanical strength. In this strategy, the SA chains are co-cross-linked by CaCl2 and cationic octa-ammonium polyhedral oligomeric silsesquioxane (Oa-POSS) particles as the first network, and an organically cross-linked poly(N-isopropyl acrylamide) (PNIPA) network is introduced into the gels as the second network. Several main results are obtained from the synthesis and characterization of the gels. For OP-PN gels, their properties depend on the content of both uniformly dispersed Oa-POSS and PNIPA network directly. The increased Oa-POSS and PNIPA network content significantly improves both the strength and resilience of gels. Relatively, the increased Oa-POSS is greatly beneficial to the modulus of gels, and the increased PNIPA network is more favorable to advancing the tensile deformation of gels. The gels with hydrophilic PNIPA network exhibit better swelling ability and remarkable temperature responsiveness, and their volume phase transition temperature can be adjusted by altering the content of Oa-POSS. The deswelling rate of gels increases gradually with the increase of POSS content due to the hydrophobic Si–O skeleton of POSS. Moreover, the enhanced drug loading and sustained release ability of the target drug bovine serum albumin displays great potential for this hybrid gel in the biomedical field.

N‐doped C‐dot embedded fluorescent and thermo‐responsive p(NIPAAm) microgel composites

In this study, the synthesis of N‐doped C‐dot embedding poly(N‐isopropylacrylamide) (p(NIPAAm)) particle composites via surfactant‐free emulsion polymerization technique was reported. The fluorescent property of N‐doped C‐dot combined with thermo‐responsive properties of p(NIPAAm) particles (p(NIPAAm)/C‐dot) render smart materials with intriguing properties. The particle size and volume phase transition temperature (VPTT) values of p(NIPAAm) based particles was altered in accord with the amount of embedded N‐doped C‐dot within p(NIPAAm) particles between 1,000–750 nm and 35.4–37.2°C, respectively. On the other hand, N‐doped C‐dot within p(NIPAAm) particles was afforded fluorescent properties with emission peak at around 460 nm. The effect of the amount of N‐doped C‐dot within p(NIPAAm) particles, temperature and pH were investigated on the fluorescent properties of N‐doped C‐dot embedded p(NIPAAm) particle composite. POLYM. COMPOS., 40:3895–3903, 2019. © 2019 Society of Plastics Engineers

Critical parameters for the controlled synthesis of nanogels suitable for temperature-triggered protein delivery

Macromolecular bioactives, like proteins and peptides, emerged as highly efficient therapeutics. The main limitation for their clinical application is their instability and potential immunogenicity. Thus, controlled delivery systems able protect the proteins prior release are highly on demand. In the present study, we developed hydrophilic thermo-responsive nanogels with tunable volume phase transition temperatures (VPTTs) and suitable features for controlled protein delivery by the use of multifunctional, dendritic polyglycerol (dPG) as macromolecular cross-linker and temperature-sensitive polymers poly(N-isopropylacrylamide) (NIPAM) and poly(N-isopropylacrylmethacrylate) as linear counterpart. We comprehensively studied the impact of the initiator, monomers and cross-linker on the nanogel structure during the synthesis. Careful analysis of the polymerization process revealed importance of balanced reactions kinetics to form particles with diameters in the range 100–200 nm and low polydispersity. We can control the cross-linking density of the nanogels mainly by the dPG feed and its degree of acrylation. In addition, our screenings revealed that the hydrophilic character of dPG enables it to stabilize the growing particles during the polymerization and thereby reduces final particle size. Co-polymerization of NIPAM and NIPMAM allows precise tuning of the VPTT of the nanogels in the desired range of 34–47 °C. Our nanogels showed outstanding high protein encapsulation efficiency and triggered cargo release upon a temperature change. The delivery efficiency of these nanogels was investigated on excised human skin demonstrating efficient dermal penetration of encapsulated proteins dependent on a temperature triggered release mechanism.

Synthesis of interpenetrating polymer networks using silicone polymer with silanol residue

Silicone polymers containing the silanol residue were prepared from a silica gel and were successively used for the synthesis of interpenetrating polymer networks (IPNs) with acrylamides, such as N-isopropylacrylamide (NIPAM) and N,N-dimethylacrylamide. During gelation, the condensation of silanols to form a siloxane linkage and the radical polymerization of acrylamides with a cross-linker simultaneously proceeded to afford IPNs composed of both the silicone polymer and polyacrylamide gels. The swelling properties of the obtained IPNs were then investigated. For example, the IPNs synthesized with NIPAM showed a much lower percentage of equilibrium mass swelling (PES) values at 3 °C in water, 378–545%, than the NIPAM polymer gel (>1500%), and in addition, these IPNs barely showed an apparent volume phase transition temperature (VPTT) in contrast to the NIPAM polymer gel.

Characterization of Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System for Controlled and Extended Release of Ranibizumab.

PurposeTo characterize a biodegradable microsphere-hydrogel drug delivery system (DDS) for controlled and extended release of ranibizumab.MethodsThe degradable microsphere-hydrogel DDSs were fabricated by suspending ranibizumab-loaded or blank poly(lactic-co-glycolic acid) microspheres within a poly(ethylene glycol)-co-(L-lactic-acid) diacrylate/N-isopropylacrylamide (PEG-PLLA-DA/NIPAAm) hydrogel. The thermal responsive behavior of various DDS formulations was characterized in terms of volume phase transition temperature (VPTT) and swelling ratios changes from 22°C to 42°C. The mechanical properties were characterized using rheological methods. Degradability of hydrogels were also examined via wet weight loss. Finally, Iodine-125 was used to radiolabel ranibizumab for characterization of encapsulation efficiency and in vitro release.ResultsAll DDS formulations investigated were injectable through a 28-gauge needle at room temperature. The VPTT increased with increase of cross-linker concentration. The swelling ratios decreased as temperature increased and were not influenced by presence of microspheres. Rheology data confirmed that increase of cross-linker concentration and microsphere loading made DDS stiffer. Increase of degradable cross-linker concentration facilitated hydrogel in vitro degradation. Controlled release of ranibizumab were achieved for investigated DDS formulations for 6 months; and increased degradable cross-linker concentration produced faster and more complete release.ConclusionsThe biodegradable DDSs are suitable for sustained release of ranibizumab. Considering ease of injection, degradability and release of ranibizumab, DDS with 3 mM cross-linker concentration and less than 20 mg/mL microsphere loadings is more favorable for future application.Translational RelevanceThe investigated DDS is promising for controlled and extended release of anti-VEGF therapeutics to achieve better treatment regimen in ocular neovascularizations.

The influence of monomer/solvent feed ratio on POEGDMA thermoresponsive hydrogels: Radiation-induced synthesis, swelling properties and VPTT

The oligo(ethylene glycol) dimethacrylate (OEGDMA), one of the most commonly utilized crosslinking monomers, was used to tailor thermoresponsive POEGDMA hydrogels by varying the monomer/solvent feed ratio (from 10 to 100 wt% of monomer). For the first time, synthesis of different POEGDMA homopolymeric networks was performed by gamma radiation, and due to the expected thermoresponsiveness their temperature-dependent properties were extensively analysed. The sol-gel study was performed as the first step after radiation-induced synthesis. The swelling properties were investigated over the wide pH (2.2–9.0) and temperature (5–80 °C) range. Characterization of structure and properties was additionally conducted by SEM, DSC, FTIR, and UV–Vis spectroscopy. The results indicated that all POEGDMA hydrogels showed a high gel content, inverse thermoresponse and volume phase transition temperature (VPTT) with no respect to initial preparation. On the other hand, by altering the monomer/solvent ratio in the prepolymerisation mixture a large diversity in the microstructure, swelling capacity and VPTT was obtained.

Preparation of colloidal molecules with temperature-tunable interactions from oppositely charged microgel spheres.

The self-assembly of small colloidal clusters, so-called colloidal molecules, into crystalline materials has proven extremely challenging, the outcome often being glassy, amorphous states where positions and orientations are locked. In this paper, a new type of colloidal molecule is therefore prepared, assembled from poly(N-isopropylacrylamide) (PNIPAM)-based microgels that due to their well documented softness and temperature-response allow for greater defect tolerance compared to hard spheres and for convenient in situ tuning of size, volume fraction and inter-particle interactions with temperature. The microgels (B) are assembled by electrostatic adsorption onto oppositely charged, smaller-sized microgels (A), where the relative size of the two determines the valency (n) of the resulting core-satellite ABn-type colloidal molecules. Following assembly, a microfluidic deterministic lateral displacement (DLD) device is used to effectively isolate AB4-type colloidal molecules of tetrahedral geometry that possess a repulsive-to-attractive transition on crossing the microgels' volume phase transition temperature (VPTT). These soft, temperature-responsive colloidal molecules constitute highly promising building blocks for the preparation of new materials with emergent properties, and their optical wavelength-size makes them especially interesting for optical applications.

PEGylated NiPAM microgels: synthesis, characterization and colloidal stability.

The objective of this work is to synthesize highly stable thermoresponsive microgels that could be used in diverse applications. To achieve this, N-isopropylacrylamide (NiPAM) based microgels were first synthesized by surfactant-free precipitation polymerization of NiPAM in the presence of poly(ethylene glycol)methacrylate (PEG) as a macro-comonomer and methylenebisacrylamide (MBA) as a chemical crosslinker. By combining a complete set of techniques such as dynamic light scattering (DLS), scanning electron microscopy (SEM), zetametry, 1H NMR and micro-differential scanning calorimetry (μDSC), we clearly demonstrate that (i) the incorporation of the PEG chains controls the size and the polydispersity of the NiPAM-based microgels, whereas the thermal behavior in solution (enthalpy, volume phase transition temperature (VPTT)) remains almost the same as for pure NiPAM microgels; (ii) the PEG chains are mainly located on the microgel periphery; and (iii) the presence of the PEG chains strongly increases the colloidal stability of microgels in electrolyte solutions at high temperatures.

Deswelling Dynamics of Thermoresponsive Microgel Capsules and Their Ultrasensitive Sensing Applications: A Mesoscopic Simulation Study

Thermoresponsive microgels with a hollow capsule architecture have been widely used in drug delivery and molecular encapsulation, and their efficacy is contingent on the internal structure in the deswelling dynamics process. Despite a large number of experimental studies on microgels, proper theoretical methods based on an individual microgel capsule are still a few because of the complexity of the microgels. Herein, we first propose a novel methodology to investigate the structural properties and deswelling dynamics of microgel capsules by integrating a temperature-dependent Morse potential with Langevin dynamics simulation. Different properties, including volume phase transition temperature, temperature-dependent diameter, and structural morphologies of individual microgels, are assessed to rationalize our simulation method, and a good agreement between simulation predictions and experimental observations has been obtained. Depending on the system temperature, the morphological transition of three regimes in the shell structure is identified: scattered nanogels, progressively porous sponge gels, and dense ribbonlike gels. The temperature-switchable sensors composed of microgel capsules on the substrates are devised, which exhibit tunable reflectivity or thickness by simply varying the system temperature. Our mesoscale results provide helpful insights into the transient structure within the networked microgels and the design of smart polymeric nanomaterials, such as biosensors, drug delivery systems, and actuators.

Interpenetrating thermophobic and thermophilic dual responsive networks

ABSTRACTPoly(N‐acryloyl glycinamide) (PNAGA)/poly(N‐isopropyl acrylamide) (PNIPAAm) interpenetrating network (IPN) hydrogels were made by UV‐light initiated radical polymerization in two‐steps. The IPN hydrogels showed a double thermoresponsive behavior due to the combination of PNIPAAm (thermophobic) and PNAGA (thermophilic) networks. Increasing the content of the thermophobic PNIPAAm network leads to a change from a broad thermophilic volume phase transition temperature of PNAGA to a thermophilic–thermophobic‐type dual transition for the prepared IPN. Due to the double thermoresponsive character of the IPN gels, the mechanical properties are dependent upon temperature as demonstrated by performing tensile tests in water at 15 and 50 °C. Furthermore, the IPN hydrogels were characterized using turbidity measurements, SEM, and the determination of the equilibrium swelling ratio. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 539–544

In situ thermal synthesis of molybdenum oxide nanocrystals in thermoresponsive microgels

In situ formation of nanocrystals within thermoresponsive microgels has become a significant technology in the fields of catalysis and biomedicine to fabricate multifunctional hybrid nanostructures. Usually, the room temperature or cooler was set to control the formation of nanocrystals using microgels as template in such process. Here, the relatively higher temperature was used to synthesize molybdenum oxide nanocrystals where the poly(N-vinyl caprolactam) microgels were found to work as both the stabilizer and the template. Specifically, ethanol was added in the solution of the microgels to raise their volume phase transition temperature (VPTT). Later, a modified hydrothermal process was performed at 70 °C with precursor molybdic acid concentrated in the microgels matrix through the hydrogen bond between molybdic acid and N-vinyl caprolactam units. 2D nanoflakes, nanorods and nanoplatelets of molybdenum oxide were successfully synthesized. Specially, the microgels with the crosslinked degree of 2% exhibited well hybrid with controlled sizes and ideal confine of the molybdenum oxide nanoplatelets within microgels, along with strong photoluminescence intensity. These results emphasized the feasibility of poly(N-vinyl caprolactam) microgels as template and stabilizer at high temperature and provided a novel synthesis strategies for hybrid microgels applicable in wide areas of nanotechnology from catalysis, sensing to therapy.

Switchable Release of Bone Morphogenetic Protein from Thermoresponsive Poly(NIPAM-co-DMAEMA)/Cellulose Sulfate Particle Coatings.

Thermoresponsive coatings of poly(N-isopropylacrylamide-co-DMAEMA)/cellulose sulfate (PNIPAM-DMAEMA/CS) complexes are reported eluting bone-morphogenetic-protein-2 (BMP-2) on demand relevant for implant assisted local bone healing. PNIPAM-DMAEMA/CS dispersions contained colloid particles with hydrodynamic radii RH = 170–288 nm at T = 25 °C shrinking to RH = 74–103 nm at T = 60 °C. Obviously, PNIPAM-DMAEMA/CS undergoes volume phase transition (VPT) analogously to pure PNIPAM, when critical VPT temperature (VPTT) is exceeded. Temperature dependent turbidity measurements revealed broad VPT and VPTT 47 °C for PNIPAM-DMAEMA/CS colloid dispersions at pH = 7.0. FTIR spectroscopy on thermoresponsive PNIPAM-DMAEMA/CS particle coatings at germanium model substrates under HEPES buffer indicated both wet-adhesiveness and VPT behavior based on diagnostic band intensity increases with temperature. From respective temperature courses empirical VPTT ≈ 42 °C for PNIPAM-DMAEMA/CS coatings at pH = 7.0 were found, which were comparable to VPTT found for respective dispersions. Finally, the PNIPAM-DMAEMA/CS coatings were loaded with BMP-2 and model protein papain (PAP). Time dependent FTIR spectroscopic measurements showed, that for T = 37 °C there was a relative protein release of ≈30% for PAP and ≈10% for BMP-2 after 24 h, which did not increase further. Heating to T = 42 °C for PAP and to 47 °C for BMP-2 further secondary protein release of ≈20% after 24 h was found, respectively, interesting for clinical applications. BMP-2 eluted even at 47 °C was found to be still biologically active.

Thermoresponsive Behavior of Magnetic Nanoparticle Complexed pNIPAm-co-AAc Microgels

Characterization of responsive hydrogels and their enhancement with novel moieties have improved our understanding of functional materials. Hydrogels coupled with inorganic nanoparticles have been sought for novel types of responsive materials, but the efficient routes for the formation and the responsivity of complexed materials remain for further investigation. Here, we report that responsive poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-co-AAc) hydrogel microparticles (microgels) are tunable by varying composition of co-monomer and crosslinker as well as by their complexation with magnetic nanoparticles in aqueous dispersions. Our results show that the hydrodynamic diameter and thermoresponsivity of microgels are closely related with the composition of anionic co-monomer, AAc and crosslinker, N,N′-Methylenebisacrylamide (BIS). As a composition of hydrogels, the higher AAc increases the swelling size of the microgels and the volume phase transition temperature (VPTT), but the higher BIS decreases the size with no apparent effect on the VPTT. When the anionic microgels are complexed with amine-modified magnetic nanoparticles (aMNP) via electrostatic interaction, the microgels decrease in diameter at 25 °C and shift the volume phase transition temperature (VPTT) to a higher temperature. Hysteresis on the thermoresponsive behavior of microgels is also measured to validate the utility of aMNP-microgel complexation. These results suggest a simple, yet valuable route for development of advanced responsive microgels, which hints at the formation of soft nanomaterials enhanced by inorganic nanoparticles.

Thermoresponsive‐interpenetrating polymer network hydrogels for heavy metal ion recovery

ABSTRACTThermoresponsive‐interpenetrating polymer network (TR‐IPN) hydrogels containing a large number of chelating groups were synthesized; the aim was to ensure the recovery of large amounts of heavy metal ions through temperature cycling across volume phase transition temperature of the hydrogel. The TR‐IPN hydrogels were synthesized from poly(N‐isopropylacrylamide) and alginate, and the ability of these hydrogels to adsorb a heavy metal ion, Cu(II), was investigated at different temperatures. In the experiment, the hydrogels were prepared using various alginate and crosslinker concentrations. Despite the incorporation of a large number of chelating groups, the TR‐IPN hydrogels exhibited a large thermoresponsive volume change regardless of the presence of Cu(II). The Cu(II) adsorption experiment showed that the saturated adsorption amount of the hydrogels was larger at 50 than at 10 °C. In addition, we demonstrated that the difference between the amounts adsorbed at 10 and 50 °C, which we consider to be the amount of Cu(II) that the TR‐IPN hydrogels can recover through temperature cycling, was greater than those obtained by other conventional copolymerized thermoresponsive hydrogels. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46701.

Electroactive, Mediating and Thermosensitive Microgel Useful for Covalent Entrapment of Enzymes and Formation of Sensing Layer in Biosensors

AbstractThermosensitive microgel particles based on the polymeric network synthesized from N‐isopropylacrylamide, sodium acrylate and N,N′‐bisacryloylcystine have been functionalized with aminoferrocene, a mediatior, and a model enzyme‐glucose oxidase (GOx). The product was very stable. A thin coating of that material has been successfully attached to the glassy carbon electrode surface to form a sensing layer. A temperature increase to a value higher than the volume phase transition temperature led to a substantial increase in the amperometric signal. That behavior was well switchable. The amperometric signal was linearly dependent on glucose concentration in the physiological concentration range. It appeared that the synthesized and functionalized microgel was a kind of microreactor and might be very useful for the construction of the platforms that can enhance the activity of enzymes in biosensors.

Significant, reversible change in microgel size using electrochemically induced volume phase transition

We have successfully synthesized a novel microgel the volume of which could be reversibly changed by using an electrochemical trigger. At appropriate potential and at human-body temperature the volume change was unusually high – by more than one order of magnitude. The starting material was a thermoresponsive microgel built from N-isopropylacrylamide, sodium acrylate and N,N′-bisacryloylcystine as the crosslinker. The gel has been modified with aminoferrocene through amid-bond formation. The influence of oxidation state of the ferrocene groups in the microgel on volume phase transition temperature was determined. The –S–S– groups from the N,N′-bisacryloylcystine linker were employed in the chemisorption of the microgel particles on the Au electrode surface and the formation of gel monolayers. It appeared that the microgel layers could be either in the shrunken- or the swollen state depending on the oxidation number of the iron atoms in the ferrocene groups. The oxidation number could be changed electrochemically and the shrunken–swollen transformation could be repeated many times. The properties of the obtained materials were examined with dynamic light scattering technique, UV–vis spectroscopy, SEM and TEM microscopies and cyclic voltammetry.

Monitoring Thermoresponsive Morphological Changes in Individual Hydrogel Microspheres.

Real-time morphology/structure changes in individual hydrogel microspheres (microgels) were directly visualized at high spatiotemporal resolution using high-speed atomic force microscopy (HS-AFM) under temperature control ranging from room temperature to ∼40 °C. The recorded HS-AFM movies demonstrate that the size and morphology of thermoresponsive poly(N-isopropyl acrylamide)-based microgels change with increasing temperature at the individual microgel level. Specifically, the height of the microgels gradually decreases and domain structures appeared even below the volume phase transition temperature. Moreover, the domain structure is retained, even after the microgels have fully collapsed. The present study thus demonstrates that temperature-controlled HS-AFM is a useful tool for monitoring stimulus-responsiveness of microgels. In the near future, it should furthermore be possible to extend this temperature-controlled HS-AFM to other stimulus-responsive materials, including autonomously oscillating microgels.

Externally Triggered Oscillatory Structural Forces.

This paper addresses triggering of oscillatory structural forces via temperature variation across an aqueous dispersion of thermoresponsive poly( N-isopropylacrylamide) (PNIPAM) nanogels confined between silica surfaces. Oscillatory structural forces are a well-known phenomenon in colloidal science, caused by interactions between molecules or colloids. Modulation of these forces usually requires changing the internal parameters of the dispersion, such as ionic strength, particle concentration, and surface charge, or changing the properties of the confining walls, such as surface roughness, potential, or elasticity. All of these parameters are usually fixed and can only be changed via exchange of the sample or the complete experimental setup. Here, a new approach is presented, combining the characteristics of smart materials with the properties of nanoparticles, using negatively charged PNIPAM nanogels. Aqueous dispersions of these nanogels express no oscillatory structural forces in the initial state (20 °C), below the volume phase transition temperature (32 °C). Heating (60 °C) reduces the nanogel size and leads to a more negative ζ-potential, which triggers the onset of oscillatory structural forces.

Thermo-sensitive Microgels Supported Gold Nanoparticles as Temperature-mediated Catalyst

Microgels with a thermo-sensitive poly(N-isopropylacrylamide) (polyNIPAm) backbone and bis-imidazolium (VIM) ionic cross-links, denoted as poly(NIPAm-co-VIM), were successfully prepared. The as-synthesized ionic microgels were converted to nanoreactors, denoted as Au@PNI MGs, upon generation and immobilization of gold nanoparticles (Au NPs) of 5–8 nm in size into poly(NIPAm-co-VIM). The content of Au NPs in microgels could be regulated by controlling the 1,6-dibromohexane/vinylimidazole molar ratio in the quaternization reaction. The microgel-based nanoreactors were morphologically spherical and uniform in size, and presented reversible thermo-sensitive behavior with volume phase transition temperatures (VPTTs) at 39–40 °C. The Au@PNI MGs were used for the reduction of 4-nitrophenol, of which the catalytic activity could be modulated by temperature.