Interactions between temperature-sensitive hydrogel microspheres and granulocytes

Poly(N-isopropylacrylamide) (PNIPAM) has a low critical solution temperature (LCST) at 32°C in water and the hydrophilicity changes through the LCST. The microspheres whose surface was composed of PNIPAM exhibited phase transition behavior around 32°C. Therefore, the interactions between PNIPAM micropheres and granulocytes depended on the temperature. That is, the oxygen consumption and active oxygen production by cells in contact with PNIPAM-containing microspheres and adhesion of the microspheres to the cell surface were more enhanced above the LCST of PNIPAM than below it, whereas no significant temperature dependence of cell–microspheres interaction was observed in nonthermosensitive microsphere systems. It was suggested that the function of cells could be controlled with temperature using the temperature-sensitive microspheres.     

Phase transition behavior of unimolecular micelles with thermoresponsive poly(N-isopropylacrylamide) coronas

This paper describes the double phase transition behavior of a thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) brush at the surface of a hydrophobic core. Reversible addition-fragmentation transfer (RAFT) polymerization of N-isopropylacrylamide (NIPAM) was conducted by using a hyperbranched polyester (Boltorn H40) based macroRAFT agent. The resultant multiarm star block copolymer (H40-PNIPAM) exists as unimolecular micelles with hydrophobic H40 as the core, densely grafted PNIPAM brush as the shell. A combination of laser light scattering (LLS) and microdifferential scanning calorimetry (micro-DSC) studies of H40-PNIPAM in aqueous solution reveals double phase transitions of the PNIPAM corona, which is in contrast to the fact that free PNIPAM homopolymer in aqueous solution exhibits a lower critical solution temperature (LCST) at approximately 32 degrees C. The first phase transition takes place in the broad temperature range 20-30 degrees C, which can be tentatively ascribed to the n-cluster-induced collapse of the inner region of the PNIPAM brush close to the H40 core; the second phase transition occurs above 30 degrees C, which can be ascribed to the outer region of PNIPAM brush. Employing the RAFT chain extension technique, the inner and outer part of PNIPAM brush were then selectively labeled with pyrene derivatives, respectively; temperature-dependent excimer fluorescence measurements further support the conclusion that the inner part of PNIPAM brush collapses first at lower temperatures, followed by the collapse of the outer part at higher temperatures.     

Release property of temperature-sensitive alginate beads containing poly(N-isopropylacrylamide)

The graft copolymer (APN) of alginate and poly(N-isopropylacrylamide) (PNIPAM) were synthesized and APN beads were prepared by dropping the aqueous solution of the copolymer into an aqueous solution of Ca(2+) solution. Alginate chains were employed to play a role in forming beads by electrostatic interactions with a multivalent ion, Ca(2+). Grafted PNIPAM segments were adopted to act as a valve for the pores of the beads, since they exhibit the properties of thermal contraction and expansion. The percent of release of blue dextran from APN beads was higher at 40 degrees C than at 25 degrees C. The difference in the release between two temperatures became more distinguishable when the content of PNIPAM in APN beads is higher. Below lower critical solution temperature (LCST), the expanded PNIPAM would close the pores of the beads, resulting in a lower release rate. Above LCST, the thermally contracted polymer would open the pores, resulting in a higher release rate. The percent of release from APN beads were investigated when the temperature of the release medium is altered. The release rate was relatively low at 25 degrees C. The temperature, however, changed up to 40 degrees C, a marked increase in the release rate was observed. These trends were found to be reproducible when the temperature was repeatedly altered between 25 and 40 degrees C. As a result, a stepwise response to the temperature alteration was obtained.     

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 ?C) 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.     

温度敏感性PNIPAM-b-PZLL-b-mPEG三嵌段共聚物的合成与自组装研究

通过大分子引发剂引发ε-苄氧羰基-L-赖氨酸-N-羧酸酐(Lys-NCA)开环聚合和大分子缩合的方法合成了聚(N-异丙基丙烯酰胺)-b-聚(ε-苄氧羰基-L-赖氨酸)-b-聚乙二醇单甲醚三嵌段共聚物(PNIPAM-b-PZLL-b-mPEG).用GPC和1H-NMR对其结构进行了表征.用芘荧光探针法证明了该三嵌段聚合物形成胶束的性质并测定了临界胶束浓度(CMC).动态光散射(DLS)研究表明,在固定PNIPAM-b-PZLL链段长度的情况下,mPEG分子量为2000时,胶束在温度高于临界溶解温度(LCST)时发生聚集,mPEG分子量为5000时,胶束在LCST以上没有发生聚集.     

Thermo-induced formation of unimolecular and multimolecular micelles from novel double hydrophilic multiblock copolymers of N,N-dimethylacrylamide and N-isopropylacrylamide

Two novel double hydrophilic multiblock copolymers of N,N-dimethylacrylamide and N-isopropylacrylamide, m-PDMAp-PNIPAMq, with varying degrees of polymerization (DPs) for PDMA and PNIPAM sequences (p and q) were synthesized via consecutive reversible addition-fragmentation chain transfer (RAFT) polymerizations using polytrithiocarbonate (1) as the chain transfer agent (Scheme 1), where PDMA is poly(N,N-dimethylacrylamide) and PNIPAM is poly(N-isopropylacrylamide). The DPs of PDMA and PNIPAM sequences were determined by 1H NMR, and the block numbers, i.e., number of PDMAp-PNIPAMq sequences (n), were obtained by comparing the molecular weights of multiblock copolymers to that of cleaved products as determined by gel permeation chromatography (GPC). m-PDMA42-PNIPAM37 and m-PDMA105-PNIPAM106 multiblock copolymers possess number-average molecular weights (Mn) of 4.62x10(4) and 9.53x10(4), respectively, and the polydispersities (Mw/Mn) are typically around 1.5. Block numbers of the obtained multiblock copolymers are ca. 4, which are considerably lower than the numbers of trithiocarbonate moieties per chain of 1 (approximately 20) and m-PDMAp precursors (approximately 6-7). PDMA homopolymer is water soluble to 100 degrees C, while PNIPAM has been well known to exhibit a lower critical solution temperature (LCST) at ca. 32 degrees C. In aqueous solution, m-PDMA42-PNIPAM37 and m-PDMA105-PNIPAM106 multiblock copolymers molecularly dissolve at room temperature, and their thermo-induced collapse and aggregation properties were characterized in detail by a combination of optical transmittance, fluorescence probe measurements, laser light scattering (LLS), and micro-differential scanning calorimetry (micro-DSC). It was found that chain lengths of PDMA and PNIPAM sequences exert dramatic effects on their aggregation behavior. m-PDMA105-PNIPAM106 multiblock copolymer behaves as protein-like polymers and exhibits intramolecular collapse upon heating, forming unimolecular flower-like micelles above the thermal phase transition temperature. On the other hand, m-PDMA42-PNIPAM37 multiblock copolymer exhibits collapse and intermolecular aggregation, forming associated multimolecular micelles at elevated temperatures. The intriguing aggregation behavior of this novel type of double hydrophilic multiblock copolymers argues well for their potential applications in many fields such as biomaterials and biomedicines.     

THERMAL-SENSITIVE BETA-CYCLODEXTRIN-CONTAINING POLY(N-ISOPROPYLACRYLAMIDE) 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.     

八乙烯基多面体低聚倍半硅氧烷-N-异丙基丙烯酰胺共聚物有机-无机杂化水凝胶的合成与表征

以N-异丙基丙烯酰胺(NIPAM)和八乙烯基笼形低聚倍半硅氧烷(OVPOSS)为单体,通过溶液自由基共聚合成了一系列P(OVPOSS-co-NIPAM)有机-无机杂化水凝胶.采用傅立叶红外光谱(FTIR)、扫描电镜(SEM)、X-射线衍射(XRD)、示差扫描量热仪(DSC)、热重分析仪(TGA)和动态粘弹谱仪(DMA)对其结构与性能进行了研究.结果表明可以通过控制投料比来调节P(OVPOSS-co-NIPAM)杂化水凝胶中POSS的实际含量;P(OVPOSS-co-NIPAM)杂化水凝胶的微观形貌为孔洞结构,随POSS含量的增加,孔径逐渐减小;所合成的P(OVPOSS-co-NIPAM)杂化水凝胶均具有温敏性,随着POSS含量的增加,其最低临界溶解温度(LCST)由33.0℃降低至30.0℃,均低于常规水凝胶(33.7℃);POSS的引入使PNIPAM水凝胶的玻璃化转变温度(Tg)由142℃升至148℃,并改善了其热稳定性和力学强度.     

THERMAL-SENSITIVE BETA-CYCLODEXTRIN-CONTAINED POLY(N-ISOPROPYLACRYLAMIDE) HYDROGELS CROSS-LINKED BY Si―O―Si BONDS

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.     

Adsorption isotherms and dissipation of adsorbed poly(N-isopropylacrylamide) in its swelling and collapsed states

Poly(N-isopropylacrylamide) (PNIPAM) physisorbed on gold surfaces in aqueous solutions has been studied using a quartz crystal microbalance with dissipation monitoring (QCM-D). The adsorption isotherms of the polymer, that is, the adsorbed mass versus the concentration of PNIPAM in solution, show distinctly different behaviors at temperatures below and above a lower critical solution temperature (LCST). Below the LCST, PNIPAM forms a single compact layer in solutions with concentrations up to 100 ppm in weight; above the LCST, much thicker films of PNIPAM form in the same concentration range. Changes in the dissipation factor versus solvent concentration show a behavior similar to those in the isotherms. The difference in the adsorption behavior below and above the LCST can be qualitatively explained in terms of the conformation difference of the polymer in its swelling and collapsed states.     

Behavior of temperature-sensitive PNIPAM confined in polyelectrolyte capsules.

Layer-by-layer assembled polyelectrolyte microcapsules are of great interest because they can possibly be used as microcontainers and they show interesting stimuli-responsive properties, which have been recently investigated. Here, we exploit capsules which are made temperature-sensitive by encapsulating poly(N-isopropylacrylamide) (PNIPAM). PNIPAM has a cloud point in water at about 32 degrees C, above which it collapses and is insoluble in water. Further this temperature responsiveness can be tuned by addition of various ions at various concentrations. Here, we present the encapsulation of PNIPAM inside polyelectrolyte microcapsules, and describe the dependence of the lower critical solution temperature (LCST) on the nature and the amount of different salts added. With this information, we demonstrate the ability to tune and finely control the collapse of encapsulated PNIPAM. In this light, this system could be used as a microsensor or drug- delivery system.     

含环糊精的温度敏感性聚合物的合成及自组装

合成了侧基含环糊精的聚异丙基丙烯酰胺(PnipamCD), 该聚合物在水溶液中具有较高的最低临界溶解温度(LCST). 快速升温到溶液的LCST以上可形成球形胶束, 慢速升温到LCST以上可形成空心囊泡. 在PNIPAM的选择性溶剂中, PnipamCD形成棒状组装体.     

Two-stage collapse of unimolecular micelles with double thermoresponsive coronas

Phase transition behavior of unimolecular dendritic three-layer nanostructures with dual thermoresponsive coronas is studied. Successive reversible addition-fragmentation transfer (RAFT) polymerizations of N-isopropylacrylamide (NIPAM) and 2-(dimethylamino)ethyl methacrylate (DMA) were conducted using fractionated fourth-generation hyperbranched polyester (Bolton H40) based macroRAFT agent. At lower temperatures (<20 degrees C), dendritic macromolecules H40-poly(N-isopropylacrylamide)-poly(2-(dimethylamino)ethyl methacrylate) (H40-PNIPAM-PDMA) exist as unimolcular core-shell-corona nanostructures with hydrophobic H40 as the core, swollen PNIPAM as the inner shell, and swollen PDMA as the corona. PNIPAM and PDMA homopolymers undergo phase transitions at their lower critical solution temperatures (LCST), which are found to be 32 degrees C for PNIPAM and 40-50 degrees C for PDMA, respectively. Upon continuously heating through the LCSTs of PNIPAM and PDMA, such dendritic unimolecular micelles exhibit two-stage thermally induced collapse. This process is reversible with a two-stage reswelling upon cooling. Laser light scattering, micro-differential scanning calorimetry, and excimer fluorescence measurements are used to investigate the double phase transitions.     

Thermo-induced formation of physical "cross-linking points" of PNIPAM-g-PEO in semidilute aqueous solutions

Linear poly(N-isopropylacrylamide) chains grafted with short poly(ethylene oxide) chains (PNIPAM-g-PEO) were prepared by free radical copolymerization of NIPAM and PEO macromonomers (M(w) = 5000 g/mol) end-capped with methacrylate in water. Temperature effects on the solution viscosity of thermally sensitive copolymer were studied in different aqueous concentrations. A specific transition was observed during the measurement of the reduced viscosities of PNIPAM-g-PEO copolymer at a certain concentration (C0) in semidilute aqueous solutions: the reduced viscosities increased sharply (namely, thermothickening behavior) at LCST when concentrations were higher than C0, or decreased sharply at LCST when concentrations lower than C0. A plateau was also found near C0 when temperature was closing to LCST from low temperature, showing there is no change in reduced viscosity under this circumstance. The inverse increase of the viscosities at higher temperatures in higher concentration (> approximately 3 g/L) is attributed to the forming of physical "cross-linking points" composed of collapsed PNIPAM core and expanded PEO shell. The sharp decrease of the viscosities at higher temperatures in lower concentration (< approximately 3 g/L) is attributed to the forming of independent globules. The plateau could be attributed to the equilibrium competition between forming of physical "cross-linking points" and independent globules depending on the copolymer solution concentrations.     

Salt effect on the heat-induced association behavior of gold nanoparticles coated with poly(N-isopropylacrylamide) prepared via reversible addition-fragmentation chain transfer (RAFT) radical polymerization

Poly(N-isopropylacrylamide) (PNIPAM) with a narrow molecular weight distribution was prepared by reversible addition-fragmentation chain transfer (RAFT) radical polymerization. A dithioester group at the chain end of PNIPAM thus prepared was cleaved by treating with 2-ethanolamine to provide thiol-terminated PNIPAM with which gold nanoparticles were coated via reactions of the terminal thiol with gold. The thermoresponsive nature of the maximum wavelength of the surface plasmon band and hydrodynamic radius (Rh) for the PNIPAM-coated gold nanoparticles were found to be sensitively affected by added salt. In pure water, Rh for the PNIPAM-coated gold nanoparticles at 40 degrees C (>lower critical solution temperature (LCST)) was smaller than that at 25 degrees C (相似文献   

具有温度敏感和荧光特性的侧链查尔酮共聚物的研究

采用2,2′-偶氮二异丁腈作为引发剂,将N-异丙基丙烯酰胺和4-甲基丙烯酰氧基-4′-二甲氨基查尔酮单体,在四氢呋喃溶剂中通过自由基共聚制备了一系列具有溶剂和温度双重敏感荧光特性的侧链查尔酮共聚物,并通过红外光谱、核磁共振氢谱和紫外-可见光谱对其结构进行表征,通过吸光度法测定了共聚物中查尔酮单元的含量.研究了侧链查尔酮共聚物的温敏性以及溶剂极性和温度双重敏感的荧光特性.结果表明,侧链查尔酮共聚物是一类具有最低临界溶解温度(LCST)的温敏性聚合物,其LCST温度随着共聚物中查尔酮含量的增加而降低;随着溶剂极性的增加,侧链查尔酮共聚物的紫外-可见最大吸收波长红移,其荧光发光波长红移并且发光强度先增强后降低,具有溶剂极性敏感的荧光特性;同时对比侧链查尔酮共聚物水溶液低温和高温下的荧光,发现低温下几乎无荧光,高温下其荧光得到明显增强,其荧光具有可逆的温度"开/关"特性。     

PNIPAM-b-聚碳酸酯温敏胶束的制备及用作药物控制释放载体的研究

以多孔硅球固定化猪胰脂肪酶(IPPL)为催化剂,温敏性HO-PNIPAM为大分子引发剂,5-甲基-5-烯丙氧羰基-三亚甲基碳酸酯(MAC)和5,5-二甲基三亚甲基碳酸酯(DTC)为共聚单体,通过开环聚合合成了不同结构比例的两亲性嵌段型共聚物P(MAC-co-DTC) -b-PNIPAM.该嵌段型共聚物在水中可自组装形成...     

Destruction of hydrogen bonds of poly(N-isopropylacrylamide) aqueous solution by trimethylamine N-oxide

Trimethylamine N-oxide (TMAO) is a compatible or protective osmolyte that stabilizes the protein native structure through non-bonding mechanism between TMAO and hydration surface of protein. However, we have shown here first time the direct binding mechanism for naturally occurring osmolyte TMAO with hydration structure of poly(N-isopropylacrylamide) (PNIPAM), an isomer of polyleucine, and subsequent aggregation of PNIPAM. The influence of TMAO on lower critical solution temperature (LCST) of PNIPAM was investigated as a function of TMAO concentration at different temperatures by fluorescence spectroscopy, viscosity (η), multi angle dynamic light scattering, zeta potential, and Fourier transform infrared (FTIR) spectroscopy measurements. To address some of the basis for further analysis of FTIR spectra of PNIPAM, we have also measured FTIR spectra for the monomer of N-isopropylacrylamide (NIPAM) in deuterium oxide (D(2)O) as a function of TMAO concentration. Our experimental results purportedly elucidate that the LCST values decrease with increasing TMAO concentration, which is mainly contributing to the direct hydrogen bonding of TMAO with the water molecules that are bound to the amide (-CONH) functional groups of the PNIPAM. We believed that the present work may act as a ladder to reach the heights of understanding of molecular mechanism between TMAO and macromolecule.     

Direct observation of the phase transition for a poly(N-isopropylacryamide) layer grafted onto a solid surface by AFM and QCM-D

The temperature-induced structural changes of a thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) layer grafted onto a silica substrate were investigated in aqueous solution using an atomic force microscope (AFM) and a quartz crystal microbalance with dissipation (QCM-D). A PNIPAM layer was grafted onto the silicon wafer surface by free radical polymerization of NIPAM to obtain a high molecular weight polymer layer with low-grafting density overall. By AFM imaging, the transition of the grafted PNIPAM chains from a brush-like to a mushroom-like state was clearly visualized: The surface images of the plate were featureless at temperatures below the LCST commensurate with a brush-like layer, whereas above the LCST, a large number of domain structures with a characteristic size of approximately 100 nm were seen on the surface. Both frequency and dissipation data obtained using QCM-D showed a significant change at the LCST. Analysis of these data confirmed that the observed PNIPAM structural transition was caused by a collapse of the brush-like structure as a result of dehydration of the polymer chains.     

Fabricated temperature sensitive photocatalyst of PNIPAM@ZnO/C for controllable photocatalytic activity

Temperature sensitive photocatalyst of PNIPAM@ZnO/C was successfully prepared by cross-linking polymerization technology and it possesses excellent and switchable photocatalytic activity.