Thermo-responsive Triblock Copolymer Research Articles

Effects of alkyl polyglucoside on the self-assembly behavior and foam properties of the thermoresponsive triblock copolymer (EO)100(PO)65(EO)100

Thermoresponsive liquid foams stabilized with the triblock copolymer (EO)100(PO)65(EO)100 (PF127) have been proved to be effective in suppressing pool fire. Understanding how the low-molecular-weight surfactants affect the properties of thermoresponsive foam stabilized by PF127 is important in the development of fluorine-free firefighting foam. In this work, the effects of the non-ionic surfactant alkyl polyglucoside (APG) on the properties of the foam stabilized by the triblock copolymer PF127 were studied. The relationships among molecular self-assembly, interfacial properties, and foam properties were investigated by conducting scattering experiments and foam aging tests. The results demonstrated that the APG molecules participated in the organization of the mixed micelles with PF127 molecules and the competition of both components in the mixed micelles affected the foaming properties. For the systems containing APG and 20 wt% PF127, APG acted as a foam inhibitor, suppressing foam generation at low concentrations. In contrast, APG acted as the foam booster at high concentrations since the mixed micelles were relatively unstable, allowing more unimers to diffuse to the interfacial region. In the absence of APG, the liquid foam from PF127 exhibited high stability and elasticity under heat due to the ordered structure formed by PF127 micelles inside the foam. As the APG concentration increased, the transition of orderly packed PF127-rich mixed micelles into disordered APG-rich mixed micelles caused the originally inhibited liquid drainage to restart rapidly, making the foams unstable upon heating. The results of this work can give theoretical guidance for the development of thermoresponsive firefighting foams.

Thermoresponsive Triblock Copolymers as Widely Applicable 19F Magnetic Resonance Imaging Tracers

Fluorine-19 magnetic resonance imaging (19F MRI) has emerged as a promising noninvasive diagnostic tool, broadening the diagnostic possibilities of commonly used proton MRI. Despite the potential of 19F MRI, an ideal tracer paving the way toward the entry of this method into common medical practice is yet to be developed. In this study, we report on a series of polymeric systems based on thermoresponsive poly[N-(2,2-difluoroethyl)acrylamide] (PDFEA), a polymer considered to be an ideal tracer for 19F MRI. The described systems are designed as BAB triblock copolymers, where B corresponds to thermoresponsive PDFEA blocks and A is a hydrophilic poly(ethylene glycol) block. These BAB triblock copolymers are able to form nanoparticles in dilute aqueous solutions, which undergo a transition into physically cross-linked hydrogels upon increasing the polymer concentration. Since thermoresponsive particle- and hydrogel-based systems are applicable in a wide range of biomedical applications, we created a diagnostic system with potential therapeutic properties (theranostic) as a widely tunable platform through straightforward synthesis while serving a multitude of applications. We analyzed the effect of the BAB block ratio on the self-assembly, thermoresponsiveness, and mechanical properties of the studied hydrogels, together with their suitability for 19F MRI. Finally, their biocompatibility was assessed on a relevant cell line.

A pH and UCST thermo-responsive tri-block copolymer (PAA-b-PDMA-b-P(AM-co-AN)) with micellization and gelatinization in aqueous media for drug release

A brand new pH and thermo-responsive amphiphilic ABC triblock copolymer of poly(acrylic acid)-block-poly(N,N-dimethyl acrylamide)-block-poly(acrylamide-co-acrylonitrile) (PAA-b-PDMA-b-P(AM-co-AN)) was applied as drug carrier systems.

Novel Fractional Purification Approach of Crude Polysaccharides via Boronic Acid-Tagged Thermoresponsive Triblock Copolymers

A novel fractional purification approach of crude polysaccharides with a boronic acid-tagged thermoresponsive triblock copolymer PEG113-b-PVBA49-b-PNIPAM105 was designed in this paper. The fractional precipitation of polysaccharides was realized through simple temperature regulation based on the difference in the lower critical solution temperatures of the triblock copolymer–dextran complex. The precipitated polysaccharides from the extracting solution was in a descending order of molecular weight. Under optimal conditions, four astragalus polysaccharide fractions (APS1, APS2, APS3, and APS4) with narrow distribution of molecular weights were obtained with the temperature-controlled fractional precipitation. The structural properties, monosaccharide compositions, and molecular weights of APS1, APS2, APS3, and APS4 were characterized by the Fourier transform infrared spectrum, Congo red spectrophotometric method, gas chromatography, and gel permeation chromatography. The differences in the biological activ...

Reactivity Control of Polymer Functional Groups by Altering the Structure of Thermoresponsive Triblock Copolymers.

A thermoresponsive ABA triblock copolymer bearing an aldehyde group on the thermoresponsive A segments was synthesized. The polymer formed a micellar assembly due to the hydrophobic interactions of the thermoresponsive segment above the lower critical solution temperature (LCST). In contrast, the ABA polymer assembly decomposed upon lowering the temperature below the LCST. Using this structural change, the reactivity of the aldehyde group toward primary amines of albumin and poly(allylamine) was investigated. When the ABA polymer assembly and reactant were mixed above the LCST, Schiff base formation was suppressed because of the aldehyde group being protected by the hydrophobic thermoresponsive core. In contrast, Schiff base formation between the ABA triblock copolymer and the primary amine moiety on the molecules was confirmed below the LCST. The reactivity of the aldehyde functional group can therefore be controlled by altering the structure of the thermoresponsive ABA polymer.

A Luminescent Thermometer Based on Linearly Thermo-responsive Copolymer and Polyoxometalates

A novel switchable luminescent thermometer based on thermo-responsive triblock copolymer poly(ethylene glycol)-b-poly(acrylamide-co-acrylonitrile-co-dimethylaminoethylmethacrylate) (PEO113-b-P(AAm264-co-AN112-co-DMA8)) and Eu-containing polyoxometalate (Eu-POM) was successfully constructed. The copolymer synthesized by RAFT exhibited a linear response to temperature variations in aqueous media, which was quite different from the uncharged copolymer P(AAm-co-AN) having a specific upper critical solution temperature (UCST). Eu-POM was surrounded around thermo-responsive blocks through electrostatic interactions, and its luminescence could be finely tuned due to the sensitivity of copolymer to the temperature variation. In cold water, POMs were trapped in highly hydrophobic cores, exhibiting an intense emission. With the upraising of temperature, the emission intensity presented a gradual decrease and showed a linear correlation with temperature. When the complex solution cooled down, the luminescence could also be perfectly restored. This temperature-luminescence correlation could be held for numerous trials, showing a potential application in thermometer.

Formation of novel thermo-responsive hybrid vesicles: influence of molar ratio of lipids and heating

Thermo-responsive triblock copolymer, [poly(2-isopropyl-2-oxazoline)-b-poly(dimethylsiloxane)-b-poly(2-isopropyl-2-oxazoline] (IDI) was synthesized, for the first time, by ring opening polymerization and it can self-assemble in to polymersome in aqueous solution. We demonstrate a simple route to develop the novel hybrid vesicles, from the IDI and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), by systematically regulating the molar ratio of DMPC. Effect of heating on the hybrid vesicular solution has also been examined. Differential scanning calorimetry (DSC), dynamic light scattering and fluorescence spectroscopy were used to investigate the role of molar ratio of DMPC and heating time of the mixture on the formation of hybrid vesicles. From DSC measurements, we interestingly found that heating the mixture of IDI and DMPC enhanced the insertion of IDI into the membrane of liposomes. The present findings confirm the potential utility of hybrid vesicular systems for the design of functional hybrid materials and could be used for controlled drug delivery applications.

Smart magnetic self-assembled micelle: an effective nanocarrier for thermo-triggered paclitaxel delivery

Magnetic micelle nanoparticles with thermoresponsive behavior were designed for thermo-triggered paclitaxel delivery. For this purpose, thermoresponsive triblock copolymer poly(N-isopropyl acrylamide)-b-polycaprolactone-b-poly(N-isopropyl acrylamide) was prepared. The magnetic micelle was formed by self-assembly of triblock copolymer on the magnetite which was coated by oleic acid. The size of the magnetic micelle was between 30–40 nm reported by transmission electron microscopy. Also, dynamic light scattering indicated the hydrodynamic diameter was thermal dependent. Moreover, the drug release profile showed thermo-triggered release of paclitaxel. Thus, the smart nanocarrier has potential to be applied in both chemotherapy and hyperthermia treatment.

Smart Nanovalves with Thermoresponsive Amphiphilic Triblock Copolymer Brushes

ABSTRACTNanochannels modified with stimuli-responsive copolymer brushes offer a smart nanovalve mechanism. The potential application of these special nanovalves is wide-ranging and includes the areas of drug delivery and signal transduction, as well as molecular machines. In this study, molecular dynamics simulations were performed to study nanovalve systems that use thermo-responsive amphiphilic triblock copolymer brushes grafted onto the surface of the nanochannel. Varying the system temperature facilitated the extension/collapse transition of the copolymer brushes, which resulted in the opening/closing of the nanochannels. The results of the investigation of the effect of the grafting density and the composition of the copolymers on the conformational transition behavior showed that the composition of copolymer has a significant influence on the nanovalve system. A remarkable result is the effectiveness of the use of intermediate or relatively low grafting density in obtaining an ideal controlling effect on the nanochannels. Our work provides a fundamental understanding of nanovalves that utilize thermo-responsive copolymers, and guidance for the design of a smart nanochannel.

The doubly thermo-responsive triblock copolymer nanoparticles prepared through seeded RAFT polymerization

The doubly thermo-responsive triblock copolymer nanoparticles of polystyrene-block-poly(N-isopropylacrylamide)-block-poly[N,N-(dimethylamino) ethyl methacrylate] (PS-b-PNIPAM-b-PDMAEMA) are successfully prepared through the seeded RAFT polymerization in situ by using the PS-b-PNIPAM-TTC diblock copolymer nanoparticles as the seed. The seeded RAFT polymerization undergoes a pseudo-first-order kinetics procedure, and the molecular weight increases with the monomer conversion linearly. The hydrodynamic diameter (Dh) of the triblock copolymer nanoparticles increases with the extension of the PDMAEMA block. In addition, the double thermo-response behavior of the PS-b-PNIPAM-b-PDMAEMA nanoparticles is detected by turbidity analysis, temperature-dependent 1H-NMR analysis, and DLS analysis. The seeded RAFT polymerization is believed as a valid method to prepare triblock copolymer nanoparticles containing two thermo-responsive blocks.

Temperature effects on the stability of gold nanoparticles in the presence of a cationic thermoresponsive copolymer

New hybrid complexes composed by a thermoresponsive copolymer and gold nanoparticles (Rh = 22 nm) have been characterized by dynamic light scattering (DLS) and UV-visible spectroscopy. A cationic thermoresponsive triblock copolymer, methoxy-poly(ethylene glycol)-block-poly(N-isopropylacrylamide)-block-poly((3-acrylamidopropyl) trimethyl ammonium chloride), abbreviated as MPEG-b-PNIPAAM-b-PN(+), has been synthesized by atom transfer radical polymerization (ATRP). We have evaluated the thermal response at low concentrations of this triblock copolymer in bulk solution and the effect of concentration on the interaction between this thermosensitive copolymer and the gold nanoparticles (AuNPs) to form new hybrid complexes (60–1000 nm) at different temperatures. The thermosensitive nature of the copolymer causes both aggregation and contraction of the aggregates at elevated temperatures. The AuNPs were found to be separately embedded in the hybrid complexes. Interestingly, the AuNPs prevent macroscopic phase separation of the system at high temperatures.

Thermo-responsive triblock copolymer phase transition behaviour in imidazolium-based ionic liquids: Role of the effect of alkyl chain length of cations

Different biophysical techniques such as fluorescence spectroscopy, dynamic light scattering (DLS), viscosity (η) and Fourier transform infrared (FTIR) spectroscopy have been carried out to characterize the effect of imidazolium-based ionic liquids (ILs) on the thermo-responsive triblock copolymer, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly-(ethylene glycol) (PEG-PPG-PEG). In addition, to demonstrate the distinct morphological changes of various self-assembled morphologies, we further employed field emission scanning electron microscope (FESEM). To investigate the effect of alkyl chain length of the cation, concentration of the ILs and the related Hofmeister series on the phase behaviour of PEG-PPG-PEG, we used a series of ILs possessing same Cl− anion and a set of cation [Cnmim]+ with increasing alkyl chain length of cation such as 1-ethyl-3-methylimidazolium chloride ([Emim][Cl]), 1-butyl-3-methylimidazolium chloride ([Bmim][Cl]), 1-hexyl-3-methylimidazolium chloride ([Hmim][Cl]) and 1-decyl-3-methylimidazolium chloride ([Dmim][Cl]). The critical micellization temperature (CMT) of the copolymer in the presence of well hydrated cations is directly correlated to their hydration. The overall specific ranking of ILs in decreasing the CMT of PEG-PPG-PEG in aqueous solution was [Emim][Cl]>[Bmim][Cl]>[Hmim][Cl]>[Dmim][Cl]. The trend of these ILs followed the well-known Hofmeister series of cations of ILs. The present study provides important information about the solution properties that can be helpful to tune the IL or temperature-sensitive copolymer CMT and micelle shapes which are crucial for understanding the drug delivery mechanisms.

Mechanistic analysis of Zein nanoparticles/PLGA triblock in situ forming implants for glimepiride.

ObjectivesThe study aims at applying pharmaceutical nanotechnology and D-optimal fractional factorial design to screen and optimize the high-risk variables affecting the performance of a complex drug delivery system consisting of glimepiride–Zein nanoparticles and inclusion of the optimized formula with thermoresponsive triblock copolymers in in situ gel.MethodsSixteen nanoparticle formulations were prepared by liquid–liquid phase separation method according to the D-optimal fractional factorial design encompassing five variables at two levels. The responses investigated were glimepiride entrapment capacity (EC), particle size and size distribution, zeta potential, and in vitro drug release from the prepared nanoparticles. Furthermore, the feasibility of embedding the optimized Zein-based glimepiride nanoparticles within thermoresponsive triblock copolymers poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) in in situ gel was evaluated for controlling glimepiride release rate.ResultsThrough the systematic optimization phase, improvement of glimepiride EC of 33.6%, nanoparticle size of 120.9 nm with a skewness value of 0.2, zeta potential of 11.1 mV, and sustained release features of 3.3% and 17.3% drug released after 2 and 24 hours, respectively, were obtained. These desirability functions were obtained at Zein and glimepiride loadings of 50 and 75 mg, respectively, utilizing didodecyldimethylammonium bromide as a stabilizer at 0.1% and 90% ethanol as a common solvent. Moreover, incorporating this optimized formulation in triblock copolymers-based in situ gel demonstrated pseudoplastic behavior with reduction of drug release rate as the concentration of polymer increased.ConclusionThis approach to control the release of glimepiride using Zein nanoparticles/triblock copolymers-based in situ gel forming intramuscular implants could be useful for improving diabetes treatment effectiveness.

Thermo-responsive triblock copolymer micelles containing PEG6000 for either water-soluble or water-insoluble drug sustained release and treatment

Thermo-responsive micelles containing PEG6000 for indomethacin and doxorubicin hydrochloride sustained release.

Thermo-responsive release of curcumin from micelles prepared by self-assembly of amphiphilic P(NIPAAm-co-DMAAm)-b-PLLA-b-P(NIPAAm-co-DMAAm) triblock copolymers

Thermo-responsive micelles are prepared by self-assembly of amphiphilic triblock copolymers composed of a poly(l-lactide) (PLLA) central block and two poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(NIPAAm-co-DMAAm)) lateral blocks, using solvent evaporation/film hydration method. The resulting micelles exhibit very low critical micelle concentration (CMC) which slightly increases from 0.0113 to 0.0144mgmL−1 while the DMAAm content increases from 31.8 to 39.4% in the hydrophilic P(NIPAAm-co-DMAAm) blocks. The lower critical solution temperatures (LCST) of copolymers varies from 44.7°C to 49.4°C in water as determined by UV spectroscopy, and decreases by ca. 3.5°C in phosphate buffered saline (PBS). Curcumin was encapsulated in the core of micelles. High drug loading up to 20% is obtained with high loading efficiency (>94%). The LCST of drug loaded micelles ranges from 37.5 to 38.0°C with drug loading increasing from 6.0 to 20%. The micelles with diameters ranging from 47.5 to 88.2nm remain stable over one month due to the negative surface charge as determined by zeta potential (−12.4 to −18.7mV). Drug release studies were performed under in vitro conditions at 37°C and 40°C, i.e. below and above the LCST, respectively. Initial burst release is observed in all cases, followed by a slower release. The release rate is higher at 40°C than that at 37°C due to thermo-responsive release across the LCST. On the other hand, micelles with lower drug loading exhibit higher release rate than those with higher drug loading, which is assigned to the solubility effect. Peppas' theory was applied to describe the release behaviors. Moreover, the in vitro cytotoxicity of copolymers was evaluated using MTT assay. The results show that the copolymers present good cytocompatibility. Therefore, the nano-scale size, low CMC, high drug loading and stability, as well as good biocompatibility indicate that these thermo-responsive triblock copolymer micelles present a good potential as carrier for targeted delivery of anticancer drugs.

Thermoresponsive self‐assembled nanovesicles based on amphiphilic triblock copolymers and their potential applications as smart drug release carriers

ABSTRACTA series of thermoresponsive triblock copolymers, methoxy poly(ethylene oxide)‐b‐poly(ε‐caprolactone)‐b‐poly(N‐isopropylacrylamide) (mPEO‐b‐PCL‐b‐PNIPAM), with different PCL and PNIPAM block lengths, were synthesized by a combination of ring opening polymerization and reversible addition‐fragmentation chain transfer polymerization techniques. The triblock copolymers undergo self‐assembly in aqueous solutions forming stable nanovesicles of various sizes with a lipid membrane structure similar to body cells as revealed by transmission electron microscopy. The nanovesicle is thermoresponsive, that is, its size is tunable using the temperature as a switch: shrinks at a temperature above the lower critical solution temperature (LCST) and expands at a temperature below the LCST. The corresponding LCST of the triblock copolymers is adjustable by varying the PNIAM segment length as well as the PCL segment length and covers a range from 33.9 to 41.0°C in water. The diameter of nanovesicles for mPEO3k‐b‐PCL5k‐b‐PNIPAM13.2k is about 177.7 nm below the LCST and 138.9 nm above the LCST, as determined by dynamic light scattering. It was demonstrated using indomethacin, a popular anti‐inflammation medicine, that the triblock copolymers can effectively act as a drug release carrier under the right human physiological conditions, that is, store the drug at a lower temperature and release it at a higher temperature, possibly targeting at the lesion sites of human body. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41361.

Functional Group-Dependent Self-Assembled Nanostructures from Thermo-Responsive Triblock Copolymers

The ability to control the formation of nanostructures through self-assembly of amphiphilic block copolymers is of great interest in the field of biology and catalysis. In this work we have studied the self-assembling behavior of a new class of thermo-responsive triblock copolymers containing poly(ethylene glycol), and demonstrated the manner in which the aggregation pattern changed on simple functional group transformation on the copolymers. Two different triblock copolymers, poly(ethylene glycol)-b-poly(N-ispropylacrylamide)-b-poly(t-butyl acrylate) (P1) and poly(ethylene glycol)-b-poly(N-isopropylacrylamide)-b-poly(glycidyl methacrylate) (P2) were synthesized using reversible addition-fragmentation chain transfer (RAFT) technique. It was observed that P1 and P2 displayed different temperature dependent solution properties in water, with P1 forming micelles above the LCST of the PNIPA while P2 showing macroscopic phase separation under similar conditions. Thereafter, the tert-butyl group of P1 was converted to the corresponding acid (P1a) and the epoxy groups of P2 was converted to diols (P2a), thus transforming the hydrophobic blocks to hydrophilic ones. Quite interestingly, such transformations led to significant changes in their self-assembling behavior, as both P1a and P2a were seen to form vesicles beyond the LCST of PNIPA. Changes in the hydrophilic fraction in the block copolymers by subtle changes in the functionality and temperature led to the formation of varied nanostructured assemblies, as evident from dynamic light scattering (DLS), transmisison electron microscopy (TEM), and steady-state fluorescence analysis. Such formation of thermo-responsive vesicles induced by simple structural changes in the copolymers is quite interesting and highly significant in drug delivery applications.

Synthesis and self-assembly behavior of thermoresponsive triblock copolymer

Block copolymers comprising thermosensitive poly(N-isopropylacrylamide) (PNIPAM) and hydrophobic poly(n-butyl acrylate) (PBA) blocks, were synthesized using the reversible addition-fragmentation chain transfer polymerization (RAFT), their thermosensitive behavior was studied by ultraviolet spectrophotometer (UV) and dynamic light scattering (DLS). The lower critical solution temperature (LCST) was strongly correlated to the hydrophobic/hydrophilic ratio of the copolymers. Their micellization and self-assembly behavior in dilute aqueous solution were studied by surface tension (SFT), DLS and TEM. The resulting block copolymers reversibly formed or deformed micellar assemblies during their LCSTs. The critical micelle concentration (CMC) was controlled by the composition of PBA and PNIPAM, indicating the successful formation of the block copolymers.

Doubly thermo-responsive ABC triblock copolymer nanoparticles prepared through dispersion RAFT polymerization

Doubly thermo-responsive triblock copolymer nanoparticles are prepared by a dispersion RAFT polymerization and the nanoparticles exhibit a two-step phase-transition with increasing temperature.

Thermo-responsive ABA triblock copolymer of PVEA-b-PNIPAM-b-PVEA showing solvent-tunable LCST in a methanol–water mixture

The thermo-responsive triblock copolymers of poly[N-(4-vinylbenzyl)-N,N-diethylamine]-block-poly(N-isopropylacrylamide)-block-poly[N-(4-vinylbenzyl)-N,N-diethylamine] containing two outer thermo-responsive blocks of poly[N-(4-vinylbenzyl)-N,N-diethylamine] (PVEA) and a central thermo-responsive block of poly(N-isopropylacrylamide) (PNIPAM) with different block lengths are synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PVEA block of the triblock copolymer shows the lower critical solution temperature (LCST) in a methanol-rich methanol–water mixture, while the PNIPAM block exhibits the LCST-type phase transition in a water-rich methanol–water mixture. It is found that the LCST of the PVEA block in the triblock copolymer increases with the polymerization degree (DP) of the PNIPAM block and decreases with the DP of the PVEA block, and the PNIPAM chain length exerts no obvious influence on the LCST of the PNIPAM block. By adjusting the water content in the methanol–water mixture and the solvent temperature, the triblock copolymer exhibits various morphologies including soluble polymer chains, flowerlike micelles containing a dehydrated PVEA core and a looped PNIPAM corona, and micellar aggregates.