Cloud Point Temperature Research Articles

Hybridization of Poly(oxazoline) and Poly(ethylene oxide)-Based Amphiphilic Copolymers into Thermosensitive Mixed Micelles of Tunable Cloud Point.

This paper reports the development in aqueous solution of mixed micelles of tunable cloud point temperature through blending in various proportions of two copolymers of different chemical natures. For that purpose, a lipid-b-poly(2-isopropyl-2-oxazoline) (lipid-b-P(iPrOx)) copolymer, self-assembling into thermosensitive micelles that phase-separate above a cloud point temperature of 38 °C, was blended in various proportions with commercial C18-b-PEOx. The latter was constituted of a hydrophobic saturated C18 chain and a hydrophilic poly(ethylene oxide) (PEO) block with varying polymerization degrees (x) and does not have any thermosensitive properties on the studied temperature range for any value of x. The different blends were thoroughly characterized by light scattering and UV-visible spectroscopy, revealing that hybridization between both copolymers always occurred, independent of the PEO block length. The resulting mixed micelles present TCP values progressively increasing with the C18-b-PEOx proportion, from 38 to 61 °C. This study demonstrates the relevance of the blending approach to tune the phase separation of micellar systems by formulation rather than by more tedious synthetic efforts. Shifting TCP through this approach extends the range of temperature where lipid-b-P(iPrOx) can find an application.

Upper Critical Solution Temperature Polymer Phase Transition as a Tool for the Control of Inorganic Salt Crystallization Process.

In this paper, the experimental research concerning the impact of the hydrophilic-hydrophobic transition of a polymer exhibiting the Upper Critical Solution Temperature (UCST) onto the crystallization process of inorganic salt is presented. A hypothesis was postulated that under favorable process conditions the sudden change of macromolecules properties and the resulting appearance of insoluble particles will induce the nucleation process of the salt. Since the transition point parameters may be precisely designed, the described mechanism would eliminate the stochastic nature of the crystallization process. Although performed experiments proved that the postulated process mechanism was incorrect, the presence of macromolecules had a significant impact on the crystallization course. The stochastic nature of the process was not eliminated; nevertheless, it seems that a specific point of nucleation was created which was independent of the cloud point temperature (TCP) of the polymer. Moreover, the surface morphology of crystals was changed.

Using 2‐isopropyl‐2‐oxazine to explore the effect of monomer distribution and polymer architecture on the thermoresponsive behavior of copolymers

AbstractPoly(cyclic imino ether)s (PCIE) have emerged as a highly promising class of polymer for use in biomedical applications with their value being derived from their excellent biocompatibility, diverse chemistry, and tunable hydrophilicity. Here, we investigate the properties of poly(2‐isopropyl‐2‐oxazine) (PiPrOz), a relatively unexplored PCIE, determining it to have a cloud point temperature (Tcp) below physiological temperature, not to crystallize from bulk or in solution, and to be highly biocompatible. Furthermore, a series of copolymers consisting of iPrOz and 2‐methyl‐2‐oxazine (MeOz) was investigated with regard to the effect of monomer distribution and polymer architecture on thermoresponsive properties. To this end, linear block and statistical co‐poly(2‐oxazine)s (co‐POz), along with three comb‐shaped POz with block or statistical POz side chains were prepared. Each of the five polymers showed distinct thermoresponsive behavior, with the linear block co‐POz undergoing micelle formation and the other polymers macroscopic phase‐separation at different Tcps. The variety observed in response to heating clearly highlights the importance of monomer sequence and polymer architecture when designing thermoresponsive polymers. We anticipate that our findings will prove useful to polymer chemists seeking to prepare novel thermoresponsive biomaterials.

Tannic Acid-Stabilized Self-Degrading Temperature-Sensitive Poly(2-n-propyl-2-oxazoline)/Gellan Gum Capsules for Lipase Delivery.

In recent years, stable hydrogen-bonded stimuli-responsive polymer capsules have been receiving great interest for the encapsulation and release of sensitive molecules such as lipase enzymes. Compartmental capsules having a liquid gel core stabilized with temperature-responsive hydrogen-bonded multilayers are advantageous over other conventional systems because of their ability to maintain hydrophilic lipase and other hydrophobic compounds in compatible protected molecular vehicle environments and prolong their native properties, e.g., in the body. In this work, we report a methodology to stabilize an aqueous liquid gellan gum (GG) core in a capsule using neutral and nontoxic building blocks, namely, poly(2-n-propyl-2-oxazoline) (PnPrOx) and tannic acid (TA), to fabricate temperature-responsive capsules, comprising both lipase and hydrophobic oil droplets. The capsules were fabricated by adding GG droplets to a PnPrOx suspension at a temperature (T) higher than its cloud point temperature (TCP). Notably, the formed capsules were not stable in water without TA stabilization via hydrogen bonding. Scanning electron microscopy (SEM) investigations of the GG/building block interphase revealed that the collapsed PnPrOx globules that are present above the TCP stabilized the GG interphase as a Pickering emulsion, while undergoing a configurational transformation into its linear form by interacting with TA in the next step of capsule formation resulting in a smooth PnPrOx/TA capsule wall. The encapsulation efficiencies of the capsules for model fluorescent molecules were found to be 52, 54, and 24% for FITC-dextran, rhodamine, and Nile red, respectively. The stability experiments exhibited swelling and shell thinning at certain locations followed by complete rupture of the capsules at 37 °C, while the capsules were stable for several weeks at temperatures below the TCP of PnPrOx. The capsules were found to be stable in stimulated gastric fluid (SGF) for several hours at 37 °C while successfully releasing the encapsulated lipase and Nile red (model hydrophobic compound) in stimulated intestinal fluid (SIF). The released lipase was found to retain almost 100% of its activity. The reported capsules have high potential for use as carriers for encapsulation and release of a variety of payloads ranging from proteins and vitamin supplements to enzymes and probiotics through the oral route of administration.

Single-chain folding and self-assembling of amphiphilic polyethyleneglycol-modified fluorinated styrene homopolymers in water solution

Amphiphilic tetrafluorostyrene monomers (EFSn) carrying in the para position a polyethyleneglycol (PEG) chain with varied lengths (n = 3–13) were synthesized and polymerized by ARGET-ATRP to obtain the corresponding amphiphilic homopolymers pEFSn-x with controlled and tailored polymerization degrees (x = 8–135). All polymers presented a reversible thermoresponsive LCST-type behavior, in water/methanol mixture when n ≤ 4 or in pure water when n ≥ 8, with a cloud point (Cp) temperature in the range 30–40 °C strictly dependent on the length of the PEG side chain. Combined small angle X-scattering (SAXS) and dynamic light scattering (DLS) measurements were used to study the self-assembly behavior in water of the water-soluble amphiphilic homopolymers. SAXS confirmed the formation of compact-sized and spherical single-chain self-folded nanostructures below Cp, that generally presented small hydrodynamic diameters (Dh ≤ 11 nm) as proven by DLS analysis. Above Cp, much larger multi-chain aggregates were formed (Dh ≥ 800 nm), that reversibly turned back to collapsed nanostructures on cooling below the Cp temperature. By contrast, the polymers were not able to self-assemble in THF or DMF solutions, in which they adopted conventional random coil conformations.

Phase equilibria and thermophysical properties of aqueous solutions of two bis(fluorosulfonyl)imide-based ionic liquids

Ionic liquids comprising bis(fluorosulfonyl)imide (FSI) anion have been recognized to be well suited for technological applications as solvent and electrolyte media. In this work, we thoroughly investigated the thermodynamic and transport behavior of binary aqueous systems of two hydrophobic FSI-based ionic liquids, namely [EMIM][FSI] and [BMPYR][FSI]. Systematic measurements of phase equilibria, density, viscosity, and electric conductivity were conducted, our aim being to provide truly reliable information that would substantially upgrade that existing in the literature. Employing DSC measurements on the neat ILs and dynamic measurements of freezing or cloud point temperatures as well as static solubility measurements for aqueous ILs, phase diagrams for both these systems over a 100 K window were established. Rather large solubilities of water in these ILs allow for measurements of various other properties in the homogeneous IL-rich region. Extensive data thus obtained on water activity in this region were correlated for each system simultaneously with the mutual liquid-liquid solubilities, using an extended SSF (Sum of Symmetrical Functions) equation. This global excess Gibbs energy model not only accurately captures all the VLE, LLE, and SLE data we determined experimentally, but also discloses an enthalpy-driven system energetics with hydrophobic hydration effects that are more pronounced in the case of [BMPYR][FSI]. The measurements of density, viscosity, and conductivity covering the systems from the neat ILs to those almost saturated with water gave positive excess volumes and negative viscosity deviations that rise and diminish, respectively, as T increases. The conductivity increases monotonously with increasing water content and temperature. Accurate functional representations were also established for the volumetric, viscosity, and conductivity data, capturing simultaneously their composition and temperature dependence. The linkage between conductivity and viscosity was further analyzed by means of the fractional Walden rule which provided excellent fits for both isopleths and isotherms and indicated comparatively weaker coupling for the [BMPYR][FSI] system and the direction of the isothermal composition changes. Finally, comparing the FSI ILs with their TFSI analogs, the former were found to be clearly less hydrophobic.

Tuning the Cloud-Point and Flocculation Temperature of Poly(2-(diethylamino)ethyl methacrylate)-Based Nanoparticles via a Postpolymerization Betainization Approach.

The ability to tune the behavior of temperature-responsive polymers and self-assembled nanostructures has attracted significant interest in recent years, particularly in regard to their use in biotechnological applications. Herein, well-defined poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA)-based core–shell particles were prepared by RAFT-mediated emulsion polymerization, which displayed a lower-critical solution temperature (LCST) phase transition in aqueous media. The tertiary amine groups of PDEAEMA units were then utilized as functional handles to modify the core-forming block chemistry via a postpolymerization betainization approach for tuning both the cloud-point temperature (TCP) and flocculation temperature (TCFT) of these particles. In particular, four different sulfonate salts were explored aiming to investigate the effect of the carbon chain length and the presence of hydroxyl functionalities alongside the carbon spacer on the particle’s thermoresponsiveness. In all cases, it was possible to regulate both TCP and TCFT of these nanoparticles upon varying the degree of betainization. Although TCP was found to be dependent on the type of betainization reagent utilized, it only significantly increased for particles betainized using sodium 3-chloro-2-hydroxy-1-propanesulfonate, while varying the aliphatic chain length of the sulfobetaine only provided limited temperature variation. In comparison, the onset of flocculation for betainized particles varied over a much broader temperature range when varying the degree of betainization with no real correlation identified between TCFT and the sulfobetaine structure. Moreover, experimental results were shown to partially correlate to computational oligomer hydrophobicity calculations. Overall, the innovative postpolymerization betainization approach utilizing various sulfonate salts reported herein provides a straightforward methodology for modifying the thermoresponsive behavior of soft polymeric particles with potential applications in drug delivery, sensing, and oil/lubricant viscosity modification.

Insights in the Thermal Volume Transition of Poly(2‐oxazoline) Hydrogels

AbstractPolymers with a lower or an upper critical solution temperature (LCST or UCST) can precipitate in a very narrow temperature range. Cross‐linking of such polymers and adding them to suited solvent results in smart gels that are capable of greatly changing their dimensions with changing temperature. This transition occurs very often in a broad temperature range, which limits the applicability of smart materials. To shed some light into the design of thermo‐responsive hydrogels with a narrow phase transition, poly(2‐ethyl‐2‐oxazoline) (PEtOx), poly(2‐isopropyl‐2‐oxazoline), and statistical copolymers of 2‐butyl‐2‐oxazoline and 2‐ethyl‐2‐oxazoline, respectively, are synthesized and the concentration‐dependent cloud point temperatures (Tcp) of the free polymers in aqueous media are determined in relation to the thermo‐responsive swelling behavior of the respective hydrogels. A narrow thermal transition of the hydrogels can only be achieved when the Tcp of the free polymers in water is independent on the concentration. Aqueous salt solutions can render even PEtOx into a concentration independent LCST polymer. However, this salt effect does not work for hydrogels.

Synthesis of Temperature-Responsive Polymers Containing Piperidine Carboxamide and N,N-diethylcarbamoly Piperidine Moiety via RAFT Polymerization.

In this study, poly(N-acryloyl-nipecotamide) (PNANAm), poly(N-acryloyl-isonipecotamide) (PNAiNAm), and poly(N-acryloyl-N,N-diethylnipecotamide) (PNADNAm) are synthesized as novel temperature-responsive polymers using reversible addition-fragmentation chain-transfer polymerization. Aqueous solutions of these three polymers are examined via temperature-dependent optical transmittance measurements. The PNANAm sample with a hydrophilic terminal group shows an upper critical solution temperature (UCST) in phosphate-buffered saline (PBS) when its molecular weight (Mn ) is 7600 or higher, whereas PNANAm (Mn < 7600) is soluble. The UCST is influenced by molecular weight and the polymer concentration. In contrast, PNANAm sample with nonionic terminal group shows UCST, when Mn is below 7600, suggesting that the terminal nonionic group possibly increases UCST of PNANAm. The urea addition experiment suggests that the driving force for expression of UCST of PNANAm is the formation of inter-and intramolecular hydrogen bonds among the polymer chains. PNAiNAm is soluble in PBS but exhibits an UCST in an appropriate concentration of ammonium sulfate. In contrast, PNADNAm exhibits a lower critical solution temperature. Comparing the chemical structure of these polymers and their phase transition behaviors suggests that the carboxamide group position in the piperidine ring could determine the UCST expression. These results could help design temperature-responsive polymers with a desired the cloud point temperature.

Synthesis and aggregation behaviour of thermo-responsive-b-poly(ionic liquid) diblock copolymers in aqueous solution

Stimuli-responsive di-block copolymers viz. poly(N-isopropylacrylamide)m-block-poly(butyl-3-vinylimidazolium bromide)n [abbreviated as PNIPAMm-b-PBVIBn m = 50 and 100, n = 54 and 115] were synthesized using RAFT (Reversible addition−fragmentation chain-transfer) polymerization. Gel permeation chromatography (GPC) and nuclear magnetic resonance (1H NMR) spectroscopy were used to characterize the block copolymer. Turbidity data shows that the lower critical solution temperature (LCST) of PNIPAM is independent of the molecular weight. No LCST behavior was estimated for PBVIB58 in an aqueous media. The addition of 2.75 M NaCl brings LCST of PBVIB58 to room temperature. The cloud point temperature (CPT) of both the block copolymers increases with an increase in the degree of polymerization of PBVIB. Scattering techniques confirm the molecular state of all the homopolymers at 28 °C in the dissolved condition. With an increase in temperature and the presence of sodium chloride (NaCl), both the copolymers remain as aggregates with PNIPAM as a core and PBVIB as a shell. The reverse structure is formed via the addition of 10 mM sodium dodecyl sulfate (SDS) into PNIPAM100-b-PBVIB54 solution.

Influence of Molecular Weight Distribution on the Thermoresponsive Transition of Poly(N-isopropylacrylamide).

A series of poly(N-isopropylacrylamide) (PNIPAm) homopolymers with narrow molecular weight distributions (MWDs) is prepared via photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The thermal transition temperature of these polymer samples is analyzed via turbidity measurements in water/N,N'-dimethylformamide mixtures, which show that the cloud point temperatures are inversely proportional to the weight average molecular weight (Mw ). Binary mixtures of the narrowly distributed PNIPAm samples are also prepared and the statistical parameters for the MWDs of these blends are determined. Very interestingly, for binary blends of the PNIPAm samples, the thermoresponsive transition is not only dependent on the Mw , which has been shown previously, but also on higher order statistical parameters of the MWDs. Specifically, at very high values of skewness and kurtosis, the polymer blends deviate from a single sharp thermoresponsive transition toward a broader thermal response, and eventually to a regime of two more distinct transitions. This work highlights the importance of in-depth characterization of polymer MWDs for thermoresponsive polymers.

Analyzing the Effects of Silica Nanospheres on the Sol-Gel Transition Profile of Thermosensitive Hydrogels.

The insertion of nanoparticles into smart hydrogels can diversify their functionalities by a synergistic combination of the components properties within the hydrogels. While these hybrid systems are attractive to the biomaterials field, careful design and control of their properties are required since the new interactions between the polymer and the nanoparticles can result in changes or the loss of hydrogels stimuli response. In order to understand the physicochemical aspects of the thermoresponsive systems, nanocomposites of poly(N-vinylcaprolactam) (PNVCL) and silica nanoparticles with different sizes and concentrations were synthesized. The UV-vis and DLS techniques showed that the PNVCL has a sharp phase transition at 34 °C, while the nanocomposites have a diffuse transition. The nanocomposites showed an initial coil-globule transition before the phase transition takes place. This was identified by the evolution of the hydrodynamic diameter of the nanocomposite globules before the cloud point temperature (Tcp), which remained constant for PNVCL. This new transition profile can be described by two stages in which microscopic volume transitions occur first, followed by the macroscopic transition that forms the hydrogel. These results show that the proposed nanocomposites can be designed to have tunable stimuli response to smaller temperature variations with the formation of intermediate globule states.

Grafting Density-Dependent Phase Transition Mechanism of Thermoresponsive Poly(glycidyl ether) Brushes: A Comprehensive QCM-D Study.

Thermoresponsive coatings that exhibit "switchable" protein- and cell-adhesive properties are frequently used for the fabrication of cell sheets. Among other architectures, polymer brush coatings have shown to be especially viable due to their distinct phase transition behavior, which can be tailored via a manifold of adjustable brush characteristics, such as the (co)monomer composition, polymer chain length, and grafting density. Brush coatings based on poly(glycidyl ether)s (PGEs) have shown to efficiently mediate cell sheet fabrication when tethered to various tissue culture substrates. Herein, we report the phase transition of self-assembled PGE brushes with respect to polymer molecular weight (M: 10 and 22 kDa) and grafting density (0.07-0.5 chains nm-2) on gold model substrates studied by quasi-static QCM-D temperature ramp measurements. The brush grafting density can be tuned via the applied grafting conditions, and all brushes investigated feature broad phase transition regimes (ΔT ∼15°C) with volume phase transition temperatures (VPTTs) close to the cloud point temperatures (CPTs) of the PGEs in solution. We further demonstrate that brush coatings with a low grafting density (0.07-0.12 chains nm-2) exhibit a continuous brush-to-mushroom transition, whereas brushes with medium grafting densities (0.3-0.5 chains nm-2) undergo a brush-to-brush transition comprising vertical phase separation during the phase transition progress. These insights help to understand the transition behavior of thin, thermoresponsive brushes prepared via grafting-to strategies and contribute to their rational design for improved functional surfaces.

Deep Learning of Binary Solution Phase Behavior of Polystyrene.

Predicting binary solution phase behavior of polymers has remained a challenge since the early theory of Flory-Huggins, hindering the processing, synthesis, and design of polymeric materials. Herein, we take a complementary data-driven approach by building a machine learning framework to make fast and accurate predictions of polymer solution cloud point temperatures. Using polystyrene, both upper and lower critical solution temperatures are predicted within experimental uncertainty (1-2 °C) with a deep neural network, Gaussian process regression (GPR) model, and a combination of polymer, solvent, and state features. The GPR model also enables intelligent exploration of solution phase space, where as little as 25 cloud points are required to make predictions within 2 °C for polystyrene of arbitrary molecular weight in cyclohexane. This study demonstrates the effectiveness of machine learning for the prediction of liquid-liquid equilibrium of polymer solutions and establishes a framework to incorporate other polymers and complex macromolecular architectures.

Controlling Growth of Poly (Triethylene Glycol Acrylate-Co-Spiropyran Acrylate) Copolymer Liquid Films on a Hydrophilic Surface by Light and Temperature.

A quartz crystal microbalance with dissipation monitoring (QCM-D) was employed for in situ investigations of the effect of temperature and light on the conformational changes of a poly (triethylene glycol acrylate-co-spiropyran acrylate) (P (TEGA-co-SPA)) copolymer containing 12–14% of spiropyran at the silica–water interface. By monitoring shifts in resonance frequency and in acoustic dissipation as a function of temperature and illumination conditions, we investigated the evolution of viscoelastic properties of the P (TEGA-co-SPA)-rich wetting layer growing on the sensor, from which we deduced the characteristic coil-to-globule transition temperature, corresponding to the lower critical solution temperature (LCST) of the PTEGA part. We show that the coil-to-globule transition of the adsorbed copolymer being exposed to visible or UV light shifts to lower LCST as compared to the bulk solution: the transition temperature determined acoustically on the surface is 4 to 8 K lower than the cloud point temperature reported by UV/VIS spectroscopy in aqueous solution. We attribute our findings to non-equilibrium effects caused by confinement of the copolymer chains on the surface. Thermal stimuli and light can be used to manipulate the film formation process and the film’s conformational state, which affects its subsequent response behavior.

Membrane Anchored Polymers Modulate Amyloid Fibrillation

The nucleating role of cellular membrane components, such as lipid moieties on amyloid beta (Aβ1-40 ) fibrillation, has been reported in recent years. The influence of conjugates fabricated from lipid anchors (cholesterol, diacylglycerol) and hydrophilic polymers on Aβ1-40 fibrillation is reported here, aiming to understand the impact of polymers cloud point temperature (Tcp ) and its hydrophobic tails on the amyloid fibrillation. Novel lipid-polymer conjugates, consisting of poly(oligo(ethylene glycol)m acrylates) and hydrophobic groups (diacylglyceryl-, cholesteryl-, octyl-, decyl-, hexadecyl-) as anchors are synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, allowing to tune the hydrophilic-hydrophobic profile of the conjugates by varying both, the degree of polymerization (n) and number of ethylene glycol units (m) in their side chain. The impact of these conjugates on Aβ1-40 fibrillation is investigated via in vitro kinetic studies and transmission electron microscopy (TEM). Hydrophobic lipid-anchors are significantly delaying fibrillation (both lag- and half times), observing similar fibrillar structures via TEM when compared to native Aβ1-40 . Other hydrophobic end groups are also delaying fibrillation of Aβ1-40 , irrespective of their "n" and "m," whereas more hydrophilic polymers (both with longer ethylene glycol-sidechains, m = 3 for octyl, decyl and m = 5 for cholesterol) are only marginally inhibited fibrillation.

Phototunable Cloud Point Temperatures Stemming from Cyclic Topology: Synthesis and Thermal Phase Transition Behavior of Cyclic Poly(N-acryloylsarcosine methyl ester).

Cyclic polymers possess distinct properties compared with their linear counterparts, such as smaller hydrodynamic volume, lower viscosity, and higher glass-transition temperature, etc. To explore the impact of the cyclic topology on the thermo-induced phase transition behavior of poly(N-acryloylsarcosine methyl ester) (PNASME), the anthracene-terminated telechelic PNASMEs are synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of monomer NASME using a bifunctional chain transfer agent (CTA) with two anthryl groups. Subsequently, cyclic PNASMEs are prepared via UV-induced cyclization under 365nm UV. There are considerable increases (up to 50°C) for the cloud point temperatures (Tcp s) of cyclic PNASMEs compared with the linear counterparts. In view of the increment, the Tcp of PNASME is tuned by varying the cyclic/linear ratio (the molar ratio between cyclic PNASME and linear PNASME in the product) with different irradiation time.

Blends of Polyisoprene with Model Styrene–Olefin Copolymers: Mixing Energetics in Blends versus Block Copolymers

Most theoretical treatments of polymer mixing thermodynamics assume that the phase behavior of both polymer blends and block copolymers is controlled by the same Flory segmental interaction parameter, χ—a quantity which is proportional to the interaction energy density, X. However, there are few comparative experimental studies on this point. This work presents a systematic experimental comparison between the interaction energy densities measured on model polydiene–polyolefin blends (Xblend) and analogous block copolymers (XBC). Experimental cloud point temperature (Tcl) curves for blends of polyisoprene (PI) with selectively saturated poly(butadiene-r-styrene) (hSBR) random copolymers are fit to the Flory–Huggins theory, and the resultant values of Xblend are corrected for critical fluctuations and for end-group contributions, wherever significant. The temperature-dependent PI/hSBR Xblend(T) and previously reported PI–hSBR XBC values show satisfactory agreement at all levels of styrene incorporation, reinforcing the conclusion that random incorporation of styrene units into the saturated polybutadiene chain significantly enhances its compatibility with PI.

Cation Template-Assisted RAFT Cyclopolymerization of Hexa(Ethylene Glycol) Di(meth)acrylates to Thermoresponsive Pseudo-Crown Ether Polymers.

Cation template-assisted reversible addition fragmentation/chain transfer (RAFT) cyclopolymerization of hexa(ethylene glycol) diacrylate (PEG6DA) or hexa(ethylene glycol) dimethacrylate (PEG6DMA) is developed as a versatile system to produce large in-chain ring cyclopolymers, thermoresponsive pseudo-crown ether polymers. For an efficient synthesis, potassium hexafluorophosphate (KPF6 ) is employed as a cation template; PEG6DA as well as PEG6DMA recognizes the potassium cation with the hexa(ethylene glycol) spacer to dynamically form a pseudo-cyclic divinyl monomer. Those monomers interacting with the potassium cations are efficiently polymerized with RAFT agents and radical initiators into cyclopolymers comprising 24-membered hexa(ethylene glycol) rings. The cation template-assisted RAFT cyclopolymerization is also effective for the synthesis of amphiphilic random cyclocopolymers bearing hydrophilic hexa(ethylene glycol) rings and hydrophobic butyl groups. Cyclopolymers of PEG6DA and PEG6DMA further show thermoresponsive solubility in water. The cloud point temperature of cyclopoly(PEG6DA)s is higher than that of a cyclopoly(PEG6DMA).

Effect of Dexamethasone on Thermoresponsive Behavior of Poly(2-Oxazoline) Diblock Copolymers.

Thermoresponsive polymers play an important role in designing drug delivery systems for biomedical applications. In this contribution, the effect of encapsulated hydrophobic drug dexamethasone on thermoresponsive behavior of diblock copolymers was studied. A small series of diblock copoly(2-oxazoline)s was prepared by combining thermoresponsive 2-n-propyl-2-oxazoline (nPrOx) and hydrophilic 2-methyl-2-oxazoline (MeOx) in two ratios and two polymer chain lengths. The addition of dexamethasone affected the thermoresponsive behavior of one of the copolymers, nPrOx20-MeOx180, in the aqueous medium by shifting the cloud point temperature to lower values. In addition, the formation of microparticles containing dexamethasone was observed during the heating of the samples. The morphology and number of microparticles were affected by the structure and concentration of copolymer, the drug concentration, and the temperature. The crystalline nature of formed microparticles was confirmed by polarized light microscopy, confocal Raman microscopy, and wide-angle X-ray scattering. The results demonstrate the importance of studying drug/polymer interactions for the future development of thermoresponsive drug carriers.