Y-shaped block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) synthesized by ATRP

Novel Y-shaped block copolymers of poly（ethylene glycol） and poly（N-isopropylacrylamide）, PEG-b-（PNIPAM）2, were successfully synthesized through atom transfer radical polymerization （ATRP）. A difunctional macroinitiator was prepared by esterification of 2,2-dichloroacetyl chloride with poly（ethylene glycol） monomethyl ether （PEG）. The copolymers were obtained via the ATRP ofN-isopropylacrylamide （NIPAM） at 30℃ with CuCl/Me6TREN as a catalyst system and DMF/H2O （v/v = 3：1） mixture as solvent. The resulting copolymers were characterized by gel permeation chromatography （GPC） and ^1H NMR. These block copolymers show controllable molecular weights and narrow molecular weight distributions （PDI 〈 1.15）. Their phase transition temperatures and the corresponding enthalpy changes in aqueous solution were measured by differential scanning calorimetry （DSC）. As a result, the phase transition temperature of PEG45-b-（PNIPAM55）2 is higher than that of PNIPAM, however, the corresponding enthalpy change is much lower, indicating the significant influence of the macromolecular composition and architecture on the phase transition.

In-Situ Synthesized Myoglobin Imprinted Poly(N-Isopropylacrylamide)/Silica Nanocomposite Gels by Using the Molecular Imprinting Method

Temperature sensitive imprinted poly(N-isopropylacrylamide) nanocomposite gels were syntheses via in-situ, free radical crosslinking polymerization of corresponding monomer in nano-sized silica and five different concentrations of myoglobin solution by using the molecular imprinting method. Mb adsorption from five different concentrations of Mb solutions was investigated by two types of nanocomposite gel systems prepared by non-imprinted and imprinted methods. Nanocomposite gels imprinted with Mb showed higher adsorption capacity and specificity for Mb than nanocomposite gels prepared by the usual procedure. The highest Mb adsorption was observed via the imprinted nanocomposite gels with 12.5% Mb. In addition, selectivity studies were also performed by using two reference molecules as fibrinogen and hemoglobin. The imprinted nanocomposite gels had higher adsorption capacity for Mb than the non-imprinted gels and also exhibited good selectivity for Mb and high adsorption rate depending on the number of Mb sized cavities.

Microwave-assisted Preparation of Temperature Sensitive Poly(N-isopropylacrylamide) Hydrogel with Improved Responsive Properties

Poly（N-isopropylacrylamide）-based hydrogel was prepared under microwave irradiation The hydrogel thus prepared, comparing with that prepared by thermal heating method, exhibits faster swelling and shrinking kinetics. The improved responsive properties are due to the more heterogeneous and porous networks formed under microwave irradiation.

Synthesis and Properties of Poly (N-isopropylacrylamide) and Poly (N-isopropylacrylamide-co-acrylamide) Hydrogels

The thermosensitive poly （ N-isopropylacrylamide ） （PNIPAAm） and poly （N-isopropylacrylamide-co-acrylamide） [ poly （NIPAAm-co-AAm） ] hydrogels with different acrylamide molar percentage are prepared by radiation polymerization using Co^60 γ-ray. Their swelling equilibrium data in the media of deionized water, NaCl aqueous solutions and different pH buffer solutions are determined. It appears that lower critical solution temperature （LCST） of the hydrogels will drop with the increase of ionic strength and increase with the rising of acrylamide content, A semi-empirical formula is set up with the experimental results. Moreover, it also indicates that this copolymer is pH-sensitive, which is similar to the homopolymer of PNIPAAm.

THE ADSORPTION OF LINEAR POLY(N-ISOPROPYLACRYLAMIDE)CHAINS ON SURFACTANT-FREE POLYSTYRENE NANOPARTICLES

The adsorption of linear poly(N-isopropylacrylamide) (PNIPAM) chains on surfactant-free polystyrene (PS) nanoparticles was used as a model system to study the hydrophobic adsorption of polymer on the surface, because the hydrophobility of PNIPAM can be continuously varied by a small temperature change. The adsorption was investigated by a combination of static and dynamic laser light scattering (LLS) measurements. In static LLS, the absolute excess scattered light intensity led to the amount of PNIPAM adsorbed on the surface. In dynamic LLS, the hydrodynamic thickness of the adsorbed PNIPAM layer was accurately measured. For a given particle concentration, the adsorption increases as the PNIPAM concentration and the incubation temperature increase. The average density of the adsorbed PNIPAM layer is reciprocally proportional to the number of the PNIPAM chains on the surface, revealing a simple scaling of the chain density distribution. The adsorption follows the Langmuir's isotherm. The enthalpy change estimated from the adsorption at 25 degrees C and 30 degrees C is slightly positive, indicating that the adsorption involves the coil-to-globule transition of the chains on the surface.

Temperature-pH Sensitive IPN Hydrogels Composed of Silk Sericin and Poly(N-isopropylacrylamide)

Interpenetrating polymer network （IPN） composed of silk sericin （SS） and poly（N-isopropylacrylamide） （PNIPAAm） was prepared. The morphology of the IPNs, in which the SS phase was stained with ammonium cuprate, was examined with TEM and a relative homogeneous distribution of the two polymers was exhibited. The swelling behavior of the IPN hydrogels showed both temperature and pH dependences.

Poly(N-isopropylacrylamide)-based Vertically Sandwich-typed Hydrogel with Fast Temperature-response Speed and Its Controlled-release Characteristics

A novel poly（N-isopropylacrylamide）-based sandwich-typed hydrogel, which was featured with both ends of linear poly（N-isopropylaerylamide） （PNIPAM） chains being grafted onto cross-linked PNIPAM chains, was successfully prepared in a three-step process by a method of sequential synthesis. The proposed hydrogel displays faster and hydration/dehydration dynamic response to temperature cycling owing to linear PNIPAM chains to form big-pore structure. This work may lead to high attraction for targeting drug delivery systems, polymeric pump, sensors and so on.

Laterally Sandwich-typed Hydrogel Columns with Liner Poly(N-isopropylacrylamide) Layer:Preparation, Swelling/deswelling Kinetics and Drug Delivery Characteristics

A novel thermo-responsive hydrogel column, featured with both ends of linear poly（N- isopropylacrylarnide） （PNIPAM） chains being grafted onto cross-linked PNIPAM chains, was reported. The laterally sandwich-typed hydrogel columns were fabricated by radical polymerization in a three-step process using a method of ice-melting synthesis. The initiating path, morphology and thermoresponsive characteristics of the prepared hydrogel columns were experimentally studied. The results show that the hydrogel column obtained by the initiator inside part has more quick swelling and deswelling rates responsing to temperature cycling than other hydrogels owing to linear PNIPAM chains to form supermacroporous structure. The proposed hydrogel structure provide a new mode of the phase transition behavior for thermo-sensitive ＂smart＂ or ＂intelligent＂ monodisperse micro-actuators, which is highly attractive for targeting drug delivery systems, chemical separations, and sensors and so on.

Thermo-Responsive Electrospun Nanofibers from Poly( N-isopropylacrylamide )/Polyvinyl Pyrrolidone Blends

A novel nanofiber composite poly(N-isopropylacrylamide)(PNIPAAm)/polyvinyl pyrrolidone(PVP)was successfully prepared by electrospinning.Analogous medicated fibers loaded with ketoprofen(KET)as a model drug were prepared.X-ray diffraction(XRD)demonstrated that the drug was presented in the fibers with an amorphous form.Both scanning and transmission electron microscopy showed that the fibers had an even diameter and smooth surface,and no phase separation was observed.The KET loaded nanofibers did not affect the morphology of the fibers,and no drug aggregation was separated from the polymer fibers.Water contact angle measurements proved that the PNIPAAm/PVP fibers switched from hydrophilic to hydrophobic when the temperature increased the lower critical solution temperature of 32℃.In vitro drug release studies were also undertaken and the result indicated that the PNIPAAm/PVP blend nanofiber presented the properties of the two polymers,having temperature-sensitive systems with sustained release properties.In addition,MTT assay demonstrated that the nanofiber film was non-toxic and suitable for cell growth.Thus,the nanofiber can be used as thermoresponsive carriers for sustained release of poor water soluble drugs.

Conformational Transition of Poly （Acrylic Acid） Detected by Microcantilever Sensing

Poly （acrylic acid） （PAA） chains are grafted on one side of a microcantilever by the self-assembled method and the deflections of the microcantilever are detected as a function of medium pH from 3 to 11. It is found that when the pH varies, the microcantilever deflects because of the changing surface stress. By analysing the electrostatic repulsive effect, the surface stress change is related to the conformation transition of PAA from a collapse state to a swelling state. This method offers the interaction information among the polymer chains during the conformational transition and affords an alternative way to study conformational change of polymers.

Preparation of poly (N-isopropylacrylamide) brush bonded on silicon substrate and its water-based lubricating property

The poly (N-isopropylacrylamide) brush was covalently bonded on an initiator-coated silicon wafer via surface-initiated atom transfer radical polymerization. The polymer brush was (76.2±0.1) nm in thickness (by ellipsometer) with a grafting density of ca. 0.27 chains/nm 2 . The tribological properties of the poly (N-isopropylacrylamide) brush were investigated by means of ball-on-disk tests in a rotational mode under water lubrication for tribological application. The experimental results exhibited a low friction coefficient of ca. 0.03. The excellent lubrication property of the brush was due to its amide groups in the polymer chains. It was supposed that the good lubrication property of the brush was attributed to the cross-linked polymer network formed by the hydrogen bond association of N-H…O==C and the water molecular layer adsorbed by the terminal amide groups in the brush. The poly (N-isopropylacrylamide) solution also exhibits a lubrication property due to physical adsorption of the polymer chains.

Preparation of poly（N-isopropylacrylamide） brush grafted silica particles via surface-initiated atom transfer radical polymerization used for aqueous chromatography

Thermoresponsive poly（N-isopropylacrylamide） （PNIPAAm） brushes were densely grafted onto silica surface via surface-initiated atom transfer radical polymeriza- tion （SI-ATRP）. The grafting reaction started from the surfaces of 2-bromoisobutyrate- functionalized silica particles in 2-propanol aqueous solution at ambient temperature using CuCIICuCI21N, N,N＇,N＇,N”.pentamethyldiethylenetriamine （PMDETA） as the catalytic system. Based on thermogravimetric analysis （TGA） results, the grafting amount and grafting density of PNIPAM chains on the surface of silica were calculated to be 1.29 mg/ m^2 and 0.0215 chains/nm^2, respectively. The gel permeation chromatography （GPC） result showed the relatively narrow molecular weight distribution （MwlMn= 1.21） of the grafted PNIPAAm. The modified silica particles were applied as high-performance liquid chromatography （HPLC） packing materials to successfully separate three aromatic compounds using water as mobile phase by changing column temperature. Temperature- dependent hydrophilic/hydrophobic property alteration of PNIPAAm brushes grafted on silica particles was determined with chromatographic interaction between stationary phase and analytes. Retention time was prolonged and resolution was improved with increasing temperature. Baseline separation with high resolution at relatively low temperatures was observed, demonstrating dense PNIPAAm brushes were grafted on silica surfaces.

THERMAL-SENSITIVE BETA-CYCLODEXTRIN-CONTAINING POLY(NISOPROPYLACRYLAMIDE)HYDROGELS CROSSLINKED BY Si—O—Si BONDS—SYNTHESIS,CHARACTERIZATION AND PROLONGING IN VITRO RELEASE OF 5-FLUOROURACIL

A series of novel p（N-isopropylacrylamide） （PNIPAM） hydrogels were synthesized by radical copolymerization of N-isopropylacrylamide （NIPAM） and 3-methacryloxypropyltrimethoxysilane （MPTMS）. The copolymers were then crosslinked through hydrolysis of the siloxane in acetic acid/water mixed solvent. Beta-cyclodextrin （Beta-CD） was introduced into the polymeric networks by condensation of 3-glycidoxypropyltrimethoxysilane derived beta-cyclodextrin （KH560-beta-CD） with MPTMS under acidic condition. These gels were heterogeneous, porous and exhibited fast deswelling kinetics when the temperature was elevated to above lower critical solution temperature （LCST）. The swelling ratios of the gels containing beta-CD at room temperature were higher than that of the normal PNIPAM hydrogel, which was caused by the lower crosslinking density in beta-CD contained gels. In comparison to that of the normal PNIPAM gel, the amount of loaded-drug in the hydrogel containing beta-CD was higher, and the release time of 5-fluorouracil （5-Fu） was prolonged, which was attributed to the formation of inclusion compounds between 5-Fu and beta-CD in gel network.

THE ■-STATE OF A SINGLE HOMOPOLYMER CHAIN IN SOLUTION

It has been an established practice to estimate the Θ-temperature of a polymer solution from thedisappearance of the interchain interactions (A_2 = 0) Recently, in studies of the temperature dependence ofthe chain conformation in solution, we found that the change of the chain conformation clearly underwentthree different stages which could be viewed as the 'gas'. 'liquid' and 'solid' states in terms of the freedomof the 'blobs' on the chain. The transition temperature between the first and second stages corresponds nicelyto the Θ-temperature determined by the conventional method. It reveals, for the first time, that the Θ-temperature can be deduced from the conformation change of a single polymer chain in solution, which isimportant not only in conception, but also in practice.

APPLICATION OF SURFACE GRAFTED POLY N-ISOPROPYL ACRYLAMIDE BY RADIATION TECHNOLOGY FOR PROTEIN SOLUTION CONCENTRATION

Poly N-isopropyl acrylamide (abbreviated as PNIPA) as a kind of thermally sensitive hydrogel is utilized to concentrate Bovin Serum Albumin (BSA) solution. In order to decrease its surface adsorption to BSA in aqueous solution, surface layer grafting of the gels by radiation technology was carried out. The results showed that hydroxyl propyl methacrylate (HPMA) grained gel exhibited a low level of BSA adsorption and still kept the original thermally sensitive properties of PNIPA hydrogels.

Technical feasibility and histopathologic studies of poly (N-isopropylacrylamide) as a non-adhesive embolic agent in swine rete mirabile

Background Non-adhesive liquid embolic agents are increasingly gaining importance in the embolization of cerebral arteriovenous malformations （AVMs）. We investigated the use of poly （N-isopropylacrylamide） （PNIPAM） as a non-adhesive embolic agent in swine rete mirabile. Methods The PNIPAM hydrogel was mixed with iohexol and embolization was performed in swine rete mirabile in 30 animals. The microcatheter was examined after embolization. Follow-up angiography was performed for embolic efficacy after embolization. Embolized retia were examined histopatholgically, and the alterations of inside rete and surrounding tissue were observed. Results The copolymer hydrogel was used for rete embolization in 30 swine, 28 swine survived the procedure, 2 swine died, 1 swine died of cerebrum infarction and the other died of embolic agent reflux into the occipital artery. The inside wall of the microcatheter was smooth, without copolymer adhering to it. Follow-up angiography was performed in 22 swine, there was no rete recanalization in 20 swine and partial rete recanalization in 2 swine because of the trunk embolization of ascending pharyngeal arteries. Histopatholgically, the copolymer was found diffused into vessels of 100-- 150 μm in diameter. In acute group, neutrophils scattered surrounding the copolymer and endothelial integrity was observed, without endothelial denuding and necrosis. In subacute and chronic groups, the copolymer was found inside retia, a few mononuclear cells and eosinocytes scattered inside and surrounding it. The muscular layer was loosened with most muscular nuclei degraded. Conclusion Experimental rete embolization with PNIPAM, made radiopaque with iohexol, is technically feasible in swine. Because of its properties, PNIPAM has great potential as a therapeutic non-adhesive embolic agent.

Thermo-responsive stick-slip behavior of advancing water contact angle on the surfaces of poly(N-isopropylacrylamide)-grafted polypropylene membranes

Wettability of a solid surface is highly important to its practical application,especially for the surface that shows thermoresponsive properties.In this paper,we describe a thermo-responsive stick-slip behavior of water droplets on the surfaces of poly(N-isopropylacrylamide)(PNIPAM)-grafted polypropylene membranes.Field emission scanning electron microscope(FESEM) images elucidate that the morphology of PNIPAM-grafted membrane surface is thermo-responsive,i.e.,the surface becomes rougher above the lower critical solution temperature(LCST) of PNIPAM.On the surface of nascent polypropylene membranes,the water droplet shows a smooth motion resulting in advancing and receding water contact angles of 111° and ～65°,respectively.On the PNIPAM-grafted membrane surfaces,the water droplet shows a stick-slip pattern above the LCST,whereas it advances smoothly below the LCST.This phenomenon is reproducible and can be ascribed to the energy barriers enhanced by the shrink of PNIPAM chains above the LCST.We also find that the slip contact angle decreases from 102° to 92° after several stick-slip cycles.This decrease is attributed to the water adsorption on the grafted PNIPAM layer,which is confirmed by the continuous decrease of the receding water contact angle.

Synthesis of thermoresponsive polystyrene-based comb-type grafted poly(N-isopropylacrylamide)

Narrowly distributed polystyrene-g-p(N-isopropylacrylamide) (PSt-g-PNIPAM) was prepared by atom transfer radical polymerization (ATRP) of N-isopropylacrylamide using the brominated polystyrene as macroinitiator and CuCl combined with hexamethyltriethylenetetramine as catalyst. Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy confirmed the structure of PSt-g-PNIPAM. The gel permeation chromatography (GPC) showed that the graft copoly- mer had a single distribution peak with molecular weight, Mn (g/mol) of 19815 g/mol (using polystyrene as the standard). Differential scanning calorimetry (DSC) revealed that due to both effects of hydro- phobic isopropyl groups and hydrogen bonds in the amide group, the glass transition temperature (Tg) of PSt-g-PNIPAM enhanced 16.0 ℃ compared to the Tg of the polystyrene.

Nano-hydroxyapatite formation via co-precipitation with chitosan-g-poly（N-isopropylacrylamide） in coil and globule states for tissue engineering application

With the excellent biocompatibility and osteo- conductivity, nano-hydroxyapatite （nHA） has shown significant prospect in the biomedical applications. Con- trolling the size, crystallinity and surface properties of nHA crystals is a critical challenge in the design of HA based biomaterials. With the graft copolymer of chitosan and poly（N-isopropylacrylamide） in coil and globule states as a template respectively, a novel composite from chitosan-g-poly（N-isopropylacrylamide） and nano-hydro- xyapatite （CS-g-PNIPAM/nHA） was prepared via co- precipitation. Zeta potential analysis, thermogravimetric analysis and X-ray diffraction were used to identify the formation mechanism of the CS-g-PNIPAM/nHA compo- site and its morphology was observed by transmission electron microscopy. The results suggested that the physical aggregation states of the template polymer could induce or control the size, crystallinity and morphology of HA crystals in the CS-g-PNIPAM/nHA composite. The CS-g-PNIPAM/nHA composite was then introduced to chitosan-gelatin （CS-Gel） polyelectronic complex and the cytocompatibility of the resulting CS- Gel/composite hybrid film was evaluated. This hybrid film was proved to be favorable for the proliferation of MC 3T3-E1 cells. Therefore, the CS-g-PNIPAM/nHA compo- site is a potential biomaterial in bone tissue engineering.

Biodegradable Microspheres with Poly(N-isopropylacrylamide) Enriched Surface: Thermo-responsibility, Biodegradation and Drug Release

Microspheres with thermo-responsible surface were fabricated by PCL-b-PEO-b-PNIPAM triblock copolymers. Thermo-responsible morphological changes of PCL-b-PEO-b-PNIPAM microspheres immersed in aqueous solution at temperatures above the LCST（e.g. 37 ℃） were observed from porous surface structure to compact surface layer. Enzymatic degradation and in vitro drug release results showed that the thermo-responsible surface layer greatly influenced the degradation of microspheres as well as the drug release behavior from microspheres. With the copolymerization of PNIPAM block into PCL-b-PEO copolymers, the drug release could be well regulated by changing temperatures and microspheres composition, which revealed the great potentials of microspheres with thermo-responsible surface for controlled drug release.