Temperature-sensitive Polymer Research Articles

Thermosensitive polylactide‐glycolide delivery systems for treatment of narcotic addictions

AbstractEnvironmental switches may be fabricated for the controlled release of pharmaceutical drug using a thermally responsive polymer with the intrinsic chemical and physical nature of stimuli‐sensitive smart materials. Particularly, much attention has been paid to the biomedical applications of poly(N‐isopropyl acrylamide) (PNIPAAm) because of its unique reversible transition at a specific lower critical solution temperature (LCST).Thermally sensitive block copolymers, poly(N‐isopropyl acrylamide‐b‐poly(L‐lactide‐co‐glycolide) (PNIPAAm‐b‐PLGA), and polyethylene glycol‐poly (lactide‐co‐glycolide) (PEG‐PLGA) triblock copolymers with different compositions and length of PLGA block were synthesized via ring‐opening polymerization of lactide and glycolide in the presence of OH‐terminated PNIPAAm or PEG. The composition and structure of the polymer were determined by NMR and FTIR. The effect of important factors, such as ionic strength, pH, and polymer concentration on the phase transition behavior of temperature‐sensitive polymers, were investigated by cloud point measurements. The resulting thermosensitive polymers were used for the entrapment of a narcotic antagonist drug, naltrexone, as the model drug. The loading efficiency and drug release behavior of naltrexone‐loaded hydrogels were investigated. The naltrexone loaded thermosensitive polymers were able to sustain the release of naltrexone for different periods of time, depending on the polymer composition, and concentration. In vitro release studies showed that these thermosensitive polymers are able to deliver naltrexone in biologically active forms at a controlled rate for 3–8 weeks. Copyright © 2009 John Wiley & Sons, Ltd.

Application of a cell sheet–polymer film complex with temperature sensitivity for increased mechanical strength and cell alignment capability

We have succeeded in fabricating a cell sheet-polymer film complex involving a temperature-sensitive polymer that has enough mechanical strength that can be manipulated even by forceps. The polymer film can be removed by lowering the temperature after transplantation, demonstrating its potential use in regenerative medicine. Recently, tissue engineering involving cell sheets was developed, tissues being fabricated by layering of these cell sheets. This technique promises high density cell packing, which is important for native cell functions, and successful heart therapy using cardiac cell sheets has been reported. On the other hand, the fabrication of a large tissue using cell sheets is difficult because of fragility of the cell sheets. Here, we have developed a novel method in which cells are attached to a temperature-sensitive poly-N-isopropylacrylamide film mixed with laminin and collagen IV, and report that the cell sheet-polymer film complex can be manipulated with forceps. A cell sheet can be removed from the polymer film by lowering the temperature after the manipulation. We have utilized this technique for the primary myocardium and fabricated a physiologically active multi-layered cardiac cell sheet. By applying a micropattern to this polymer film, we have succeeded in making a skeletal muscle cell sheet in which myotubes are oriented in the desired direction. Overall, we showed that this method is useful for cell sheet manipulation, morphogenesis, and transplantation.

Foam Films from Thermosensitive PNIPAM and SDS Solutions

Thin liquid foam films stabilized with the addition of a temperature-sensitive neutral polymer, poly(N-isopropylacrylamide) (PNIPAM), in the presence of varying amounts of an anionic surfactant, SDS, were investigated using the thin-film balance. Data were analyzed in light of new and previously reported neutron reflectivity data describing the adsorption behavior of PNIPAM/SDS mixtures at the single air-water interface. In the case of thin films prepared from pure polymer solutions, unexpectedly thick and stable films were observed, and increases in solution temperature or polymer molecular weight induce corresponding increases in the thin-film thickness. This behavior is attributed to a stabilization of the films by repulsive entropic forces between long dangling polymer tails adsorbed at the interfaces. The addition of SDS causes a striking decrease in the thin-film thickness that is very well correlated with the desorption of polymer chains from the interface resulting from polymer-surfactant interactions in the bulk. Upon SDS introduction, repulsive forces stabilizing the films vary from purely entropic forces for small amounts of surfactant to supramolecular oscillatory forces at high SDS concentrations, whereas a combination of electrostatic and entropic forces is expected in intermediate concentration regions. Properties of thin films made from PNIPAM and SDS are thus highly sensitive to parameters such as the polymer-surfactant ratio, temperature, and molecular weight, offering precise control of the thin-film thickness that could be used to tailor foam characteristics.

Evaluation of a Novel Temperature-Sensitive Polymer for Temporary Ureteral Occlusion

Proximal stone migration during ureteroscopic procedures increases operative time and risk. This study was designed to evaluate the ability of a new temperature-sensitive polymer to prevent proximal stone migration during ureteroscopic procedures. Porcine urinary systems were harvested en bloc. The volume of gel needed to occlude the ureter, time to achieve a solid state, length of ureter filled, and pressure needed to dislodge the gel from the ureter were recorded. Radio opacity of the polymer was evaluated. Endoscopic laser lithotripsy was the performed after deploying the urologic polymer, and, after gel application and stone manipulation, all ureters were examined for histologic changes. At 36.7 degrees C, 0.5 mL and 1 mL of polymer sufficiently occluded the ureter. Both amounts solidified in 25 to 40 seconds. The mean length of ureter occluded was 56.3 mm, and the mean pressure needed to dislodge the polymer was 159.2 mm Hg. The polymer was radiopaque and did not cause histologic alterations in the ureter. Proximal migration of stone fragments was not observed during any of the procedures performed. Our in vitro study indicates that this radiopaque, thermosensitive polymer is able to transiently occlude the ureter without damaging the urothelium while withstanding the pressure of ureteroscopic irrigation, stone motion, and laser energy.

Polimery wrazliwe na bodzce (I)

In recent years much interest has been focused on the materials that respond to external stimuli such as temperature, pH, light or presence of biochemical compounds. So called stimuli-sensitive (,,smart or intelligent) structures are of significant scientific and technological importance. They are used to construct devices, also nano- and microdevices for a variety of applications in the delivery of therapeutics, tissue engineering, bioseparation, sensors or actuators and many others. This review focuses on the stimuli-sensitive polymers and their potential application. In the first part the fundamentals of the behavior in solution of temperature and pH sensitive polymer materials are discussed. Basic information on other stimuli responsive polymers (photo- and biochemical sensitive systems, dual sensitive polymers) are also given. The next paper will be devoted to the application of stimuli-sensitive polymer materials in various areas.

Magnetic and temperature-sensitive composite polymer particles and adsorption behavior of emulsifiers and trypsin

A combination of magnetic and temperature-responsive properties in the same polymer composites is expected to increase their potential applications in the biomedical field. Accordingly, micron-sized magnetite/polystyrene/ poly(2-dimethylaminoethyl methacrylate-ethyleneglycol dimethacrylate), which are abbreviated as Fe3O4/PS/P (DM-EGDM) composite polymer particles, were prepared by the seeded copolymerization of DM and EGDM in the presence of magnetite/polystyrene (Fe3O4/PS) particles. Fe3O4/PS/P(DM-EGDM) composite particles with magnetic properties showed a temperature-sensitive phase transition at approximately 31 °C. The adsorption behavior of the low molecular weight emulsifiers and trypsin (TR) as biomolecules were examined on Fe3O4/PS/P(DM-EGDM) composite polymer particles at different temperatures. The native conformation of TR was followed by measuring the specific activity under various adsorption conditions. The activity of the adsorbed TR on composite polymer particles was higher than those of the free TR and TR adsorbed on Fe3O4/PS particles.

A viscosity-tunable polymer for DNA separation by microchip electrophoresis

A thermo-responsive separation matrix, consisting of Pluronic F127 tri-block copolymers of poly(ethylene oxide) and poly(propylene oxide), was used to separate DNA fragments by microchip electrophoresis. At low temperature, the polymer matrix was low in viscosity and allowed rapid loading into a microchannel under low pressure. With increasing temperatures above 25 degrees C, the Pluronic F127 solution forms a liquid crystalline phase consisting of spherical micelles with diameters of 17-19 nm. The solution can be used to separate DNA fragments from 100 bp to 1500 bp on poly(methyl methacrylate) (PMMA) chips. This temperature-sensitive and viscosity-tunable polymer provided excellent resolution over a wide range of DNA sizes. Separation is based on a different mechanism compared with conventional matrices such as methylcellulose. To illustrate the separation mechanism of DNA in a Pluronic F127 solution, DNA molecular imaging was performed by fluorescence microscopy with F127 polymer as the separation matrix in microchip electrophoresis.

Phase Transition of Temperature-Sensitive Polymer Gels

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Preparation of Micrometer-Sized, Monodisperse “Janus” Composite Polymer Particles Having Temperature-Sensitive Polymer Brushes at Half of the Surface by Seeded Atom Transfer Radical Polymerization

Micrometer-sized, monodisperse polystyrene (PS)/poly[methyl methacrylate-(chloromethyl)styrene] [P(MMA-CMS)] composite particles having hemispherical structure were prepared by solvent evaporation from toluene droplets containing dissolved PS and P(MMA-CMS) dispersed in aqueous solution, which had been prepared using the membrane method. The formation of hemispherical ("Janus") morphology by phase separation between the PS and the P(MMA-CMS) was confirmed by both optical and electron microscopy. Atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DM) was subsequently carried out in the presence of hemispherical PS/P(MMA-CMS) composite particles in an aqueous dispersed system. After polymerization, the morphology of the particles changed from spherical to "mushroom" shape as observed by scanning electron microscopy, indicating that DM polymerized inside or on the surface of half [P(MMA-CMS) phase] of the particles. 1H NMR spectra were consistent with chloromethyl functional groups in P(MMA-CMS) operating as ATRP initiators in the DM polymerization.

2P-138 温度感受性ポリマーを利用した筋細胞シートの作製(筋肉(筋蛋白質・収縮),第46回日本生物物理学会年会)

2P-138 温度感受性ポリマーを利用した筋細胞シートの作製(筋肉(筋蛋白質・収縮),第46回日本生物物理学会年会)

Polystyrene microbeads modified with an elastin-like biopolymer for stimuli-responsive immunodetection

An efficient and controlled method for immunodetection, using polystyrene (PS) microbeads conjugated with an elastin-like polypeptide (ELP), was investigated. ELP is a temperature-sensitive polymer that exhibits a hydrophilic–hydrophobic phase transition at the lower critical solution temperature. To introduce amine groups, ELP was modified with lysine for conjugation with PS microbeads functionalized with carboxylic groups. Prostate-specific antigen (PSA), a cancer marker, was detected from a biomolecular mixture using ELP-conjugated PS microbeads and ELP-conjugated antiPSA. External stimuli were used to reversibly separate the PSA–antiPSA complex. The stimuli-responsiveness of the ELP provided a designable generic biosurface for diagnostic detection.

最新のキャピラリー電気泳動とチップ電気泳動 キャピラリー・マイクロチップ電気泳動のための粘性可変分離媒体

Various kinds of functional polymers have been developed for capillary and microchip electrophoresis. A versatile alternative to entangled and random-coiled polymers, Pluronic F127, is a typical functional polymer for a DNA separation matrix in microchip electrophoresis. This temperature-sensitive and viscosity-tunable polymer provided excellent resolutions over a wide range of DNA sizes based on a different separation mechanism compared with conventional polymers such as cellulose-derivatives. In this review, we will describe different type of viscosity-tunable polymers as well as our recent work using Pluronic F127.

Selective synthesis of double temperature-sensitive polymer–peptide conjugates

A novel synthetic route has been developed to couple selectively a modified octa-peptide, that is able to gel at low temperature, to the prototypical thermoresponsive polymer poly(N-isopropylacrylamide) to give a bioconjugate that exhibits double thermoresponsiveness.

Synthesis and solution behaviour of temperature sensitive water soluble polymers bearing alkylaryl hydrophobes

A kind of temperature sensitive polymers of acrylamide (AM) and 3-isopropenyl-α,α-dimethylbenzyl urethane (macromer) were synthesised by free radical aqueous solution copolymerisation. Their molecular structures were verified by 1H NMR and fourier transform infrared (FTIR) spectroscopy. Some factors affecting synthesis, such as macromer content, initiator concentration, reaction temperature as well as solution behaviours of these polymers were studied. The results show that these factors have significant effect on the performance of the products, the optimum reaction conditions are 1·8 mol-% macromer, 0·4 wt-% initiator and 35°C. The copolymer solutions exhibit good thermothickening behaviour. Even at 0·15 wt-% polymer solution, a typical thermothickening behaviour can be seen. The higher the polymer concentration, the more prominent the thermothickening behaviour of polymer solution. The polymer solutions show shear thickening behaviour.

High density self assembled nanoparticle film with temperature-controllable interparticle spacing for deep sub-wavelength nanolithography using localized surface plasmon modes on planar silver nanoparticle tunable grating

A novel photolithographic technique using a periodic hexagonal close packed silver nanoparticle 2D array photo mask has been demonstrated to transfer a nano-pattern into a photoresist using G–I line proximity photolithography. This method can be made to precisely control the spacing between nanoparticles by using temperature. The high-density nanoparticle thin film is accomplished by self assembly through the Langmuir-Schaefer (LS) technique on a water surface and then transferring the particle monolayer to a temperature sensitive polymer membrane. A 30 nm hexagonal close packed silver nanoparticle 2D array pattern with a 50 nm period has been successfully transferred into S1813 photoresist using I-line exposure wavelength. The resultant feature sizes were 34 nm with a period of 46 nm, due to the surface plasmon resonance where the S1813 photoresist feature is approximately 11 times smaller than I-line exposure wavelength.

Polymeric Actuators for Biological Applications

To shed light on the role of cell rheology and mechanotransduction in various physiological and disease states, different techniques of force application, such as optical tweezers and deformable substrates, are employed. In this present paper we describe a new approach for the deformation of cells based on the temperature-sensitive polymer poly(N-isopropylacrylamide), PNIPAM. In response to temperature changes, PNIPAM gels undergo extensive and reversible changes in volume that allow them to be used as actuators for stretching and compressing cells and tissues. Herein we focus mainly on our experience with the deformation of red blood cells as proof of principle, and demonstrate the wealth of possibilities such stimuli-responsive materials may offer as actuators.

Atomic Layer Deposition for Nano-Fabrication of 3D Optoelectronic Devices

We present recent investigations of the atomic layer deposition (ALD) of high transparency, high index, luminescent, and optoelectronic materials into self-assembled opal, lithographic, and biologically derived templates. Investigations on inverse opal based structures, which have the potential to sustain a complete photonic band gap, are presented and have been infiltrated with depositions of TiO2, Al2O3, ZnS:Mn and GaP. It is demonstrated that derivatives of the opal structure can be obtained by the use of a sacrificial buffer layer technique. Consequently, structures can be inverted, precisely replicated, and formed from composite or multilayered materials that allow a high degree of functionality. Additionally, this process enables temperature-sensitive polymer structures to be inverted by low temperature ALD to a high temperature compatible material that then serves as a high temperature template. Recent work is presented on the application of this technique to tune the properties of 2D photonic crystal slab waveguides and for the coating of biological scaffolds.

Deterministic control of plasma-assembled self-organized Ge∕Si quantum dot arrays

Self-assembly of size-uniform and spatially ordered quantum dot (QD) arrays is one of the major challenges in the development of the new generation of semiconducting nanoelectronic and photonic devices. Assembly of Ge QD (in the ∼5−20 nm size range) arrays from randomly generated position and size-nonuniform nanodot patterns on plasma-exposed Si(100) surfaces is studied using hybrid multiscale numerical simulations. It is shown, by properly manipulating the incoming ion/neutral flux from the plasma and the surface temperature, the uniformity of the nanodot size within the array can be improved by 34%−53%, with the best improvement achieved at low surface temperatures and high external incoming fluxes, which are intrinsic to plasma-aided processes. Using a plasma-based process also leads to an improvement (∼22% at 700 K surface temperature and 0.1 ML∕s incoming flux from the plasma) of the spatial order of a randomly sampled nanodot ensemble, which self-organizes to position the dots equidistantly to their neighbors within the array. Remarkable improvements in QD ordering and size uniformity can be achieved at high growth rates (a few nm∕s) and a surface temperature as low as 600 K, which broadens the range of suitable substrates to temperature-sensitive ultrathin nanofilms and polymers. The results of this study are generic, can also be applied to nonplasma-based techniques, and as such contributes to the development of deterministic strategies of nanoassembly of self-ordered arrays of size-uniform QDs, in the size range where nanodot ordering cannot be achieved by presently available pattern delineation techniques.

DEVELOPMENT OF AN INJECTABLE PH- AND TEMPERATURE-RESPONSIVE HYDROGEL DRUG DELIVERY SYSTEM.

Regions of local acidosis, such as that seen in myocardial ischemia, offer a target for stimuli-sensitive drug delivery systems. Hydrogels are polymer networks that are capable of entrapping significant amounts of water and can be designed to respond to stimuli such as temperature, pH, light, and electric fields. These properties make them highly attractive for drug delivery systems because of their biocompatibility and potential for drug targeting. In particular, reversible hydrogels are attractive because they can be designed to be soluble under normal physiologic conditions but form a gel under other conditions, such as decreased pH. In this study, we investigated the sol-gel properties of a pH- and temperature-sensitive polymer and assessed the ability of this polymer to be developed into an injectable hydrogel drug delivery system for ischemic cardiac tissue. Poly(N-isopropylacrylamide-co-propyl acrylic acid) (p(NIPAAm-co-PAA)) was synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. The feed composition of the pH-sensitive component, PAA, was varied between 0 and 20 mol%. Polymer was characterized by gel permeation chromatography and proton nuclear magnetic resonance to determine the molecular weight and polymer composition, respectively. Polymer samples were dissolved in phosphate buffer, and then pH was adjusted between 4.5 and 7.0. One-milliliter samples were loaded onto a rheometer to quantify viscoelastic properties. P(NIPAAm-co-PAA) polymers of varying PAA content were successfully synthesized by RAFT. At physiologic pH (7.4), the polymer did not form a gel but rather remained in the soluble state at all temperatures. However, at low pH (below approximately pH 5.5), with increasing temperature (in a physiologically relevant range), the polymers underwent a phase change from a clear liquid, to a cloudy liquid, and finally to a gel. As the pH was decreased further, the gelation temperature for a given polymer composition also decreased. In conclusion, by varying the relative ratio of NIPAAm and PAA in p(NIPAAm-co-PAA), the temperature and pH at which a gel forms can be controlled. Future studies will investigate the drug-release properties of this system.

Reversible Cell Deformation by a Polymeric Actuator

Mechanical forces applied to a living cell affect its development and morphology. The application of different physical forces to a cell provides valuable insights into its rheology, mechanotransduction, and mechanosensing. Here we report on the fabrication and use of polymeric actuators for the reversible deformation of cells. The temperature sensitive polymer poly (N-isopropylacrylamide) was applied in different ways to red blood cells as a model system, demonstrating a wealth of actuating possibilities. Such polymeric actuators may serve as powerful tools in studies of cell biology and biomechanics beause of their ease of preparation and the extensive range of chemical modifications that can be utilized.