温度感应复合型控制释放膜系统的性能研究

采用等离子诱导填孔接枝聚合法将聚N-异丙基丙烯酰胺(PNIPAM)开关接枝到聚偏氟乙烯膜(PVDF)膜孔上,同自由基聚合法制备的PNIPAM交联水凝胶结合,成功地组成了一种温度感应复合型控制释放膜系统。在该膜系统中,PNIPAM接枝PVDF膜作为控制释放开关,PNIPAM交联水凝胶作为药物载体。通过改变交联水凝胶和开关膜的微观结构,研究了该复合膜系统的温度感应控制释放特性。结果表明,该复合膜系统具有良好的温度感应特性,优于单独的开关膜控制释放系统或是单独的交联水凝胶控制释放系统。研究结果将为温度感应型控制释放系统或给药系统的设计与开发提供理论基础。     

PNIPAM/锂藻土纳米复合凝胶微球的制备及其弹性力学性能

利用微流控技术,以锂藻土作为交联剂,成功制备得到温度响应型聚（N-异丙基丙烯酰胺）（PNIPAM）与锂藻土的纳米复合凝胶微球,并利用一种简单的微步进单轴压缩装置,分别在25℃和37℃下对具有不同锂藻土含量的PNIPAM/锂藻土纳米复合凝胶微球的弹性力学性能进行系统研究。该微步进单轴压缩装置主要包括三个部分：一个程控进样器用以实现对凝胶微球的微步进压缩,一套配有高分辨率数码相机的侧视光学系统用以记录凝胶微球受压时发生的形变,一台精密电子天平作为力传感器用来记录凝胶微球在特定形变下所受的外力。研究结果表明,纳米复合凝胶微球在25℃和37℃下的形变量H与所受压力F的实验数据与Hertz弹性接触理论方程呈现良好的拟合关系,证明了PNIPAM/锂藻土纳米复合凝胶微球在25℃和37℃下均具有弹性形变行为。同时,随着锂藻土含量的增加,PNIPAM/锂藻土纳米复合凝胶微球的温敏性降低,但其杨氏模量增大。具有相同锂藻土含量的纳米复合凝胶微球,由于温度升高凝胶体积收缩、凝胶结构变得致密,因此在37℃下的杨氏模量大于其在25℃下的杨氏模量。研究结果可为PNIPAM/锂藻土纳米复合凝胶微球的设计与实际应用提供指导。     

Synthesis and photo-controllable thermosensitivity of poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) terminated with dimethylaminochalcone unit

Poly(N-isopropylacrylamide) terminated with dimethylaminochalcone unit (DMAC-terminated PNIPAM) were prepared by reversible addition-fragmentation chain transfer polymerization using dimethylaminochalcone-functionalized trithiocarbonate (TTC-DMAC) as chain transfer agent. Photodimerization of DMAC-terminated PNIPAM was confirmed by UV-Vis, fluorescence and GPC measurements. The lower critical solution temperature (LCST) of DMAC-terminated PNIPAM first increases and then decreases with increasing molecular weight. When subjected to 365 nm UV irradiation, a large increase of the LCST of DMAC-terminated PNIPAM has been observed especially in the polymer with low molecular weight. Furthermore, the LCST increases with increasing time of 365 nm UV irradiation, which shows photo-controllable thermosensitivity of DMAC-terminated PNIPAM.     

温敏性微凝胶对蛋白质和酶的吸附性能

用微乳液聚合方法以N-异丙基丙烯酰胺为单体合成了温敏性微凝胶聚N-异丙基丙烯酰胺(PNIPAM),研究了其对两种蛋白质和两种酶的吸附性能,测定了吸附等温线和温度对吸附量的影响。结果表明,微凝胶在低临界溶解温度(LCST)附近吸附蛋白质和酶的量有一突跃,例如在LCST前后,1 g纳米颗粒吸附的酪蛋白的质量分别为225 mg和415 mg;吸附的枯草杆菌蛋白酶的质量分别为12 000U/mg和27 500 U/mg。蛋白质和酶是通过物理吸附作用结合到PNIPAM微凝胶上,可以用调节温度的方法,来控制温敏微凝胶对蛋白质和酶的吸附与脱附。     

Synthesis and thermo-responsive behavior of fluorescent labeled microgel particles based on poly(N-isopropylacrylamide) and its related polymers

Poly(N-isopropylacrylamide) (PNIPAM) microgel particles labeled with 3-(2-propenyl)-9-(4-N,N-dimethylaminophenyl)phenanthrene (VDP) as an intramolecular fluorescent probe were prepared by emulsion polymerization. The thermo-responsive behavior of the VDP-labeled PNIPAM microgel particles dispersed in water was studied by turbidimetric and fluorescence analyses. The transition temperature of the VDP-labeled PNIPAM microgel particles in water determined by turbidimetric analysis was ca. 32.5 °C. The wavelength at the maximum fluorescence intensity of the VDP units linked directly to the microgel particles dramatically blue-shifted around the transition temperature. In addition it gradually blue-shifted even below the transition temperature where there was no change observed in the turbidity. These findings suggest that the gradual shrinking of microgel particles occurs with increasing temperature and the subsequent dramatic shrinking results in the increasing in the turbidity. The transition temperatures of VDP-labeled poly(N-n-propylacrylamide) and poly(N-isopropylmethacrylamide) microgel particles determined by turbidimetric analysis were ca. 23 and ca. 42.5 °C, respectively, and their thermo-responsive behavior was similar to that for the VDP-labeled PNIPAM system. In these three systems the microenvironments around the fluorescent probes above the transition temperatures became more hydrophobic than those below the transition temperature, and the estimated values of microenvionmental polarity around the VDP units on their collapsed states were almost the same.     

Structure and performance of poly(vinylidene fluoride) membrane with temperature‐sensitive poly(n‐isopropylacrylamide) homopolymers in membrane pores

The poly(vinylidene fluoride) (PVDF)/poly(N‐isopropylacrylamide) (PNIPAM) blend membranes with different PNIPAM contents are prepared by phase inversion of PNIPAM and PVDF in aqueous medium. The membranes are characterized by thermal gravimetric analyses, elemental analysis, Fourier transform infrared spectrometer, X‐ray photoelectron spectroscopy, and scanning electron microscope photographs. The results indicate that PNIPAM chains are largely distributed in membrane pore other than membrane surface, and furthermore, with the increase of PNIPAM content, the porous size, porosity, and water flux through the membrane increase, the hydrophilicity and antiprotein fouling are enhanced. The blend membrane exhibits temperature‐sensitive permeability to aqueous solutions, with the most drastic change being observed at the lower critical solution temperature (LCST) of PNIPAM (around 32°C). Below the LCST, the blend membrane shows a high protein rejection and a low water flux; above the LCST, the blend membrane shows a low protein rejection and a high water flux. POLYM. COMPOS., 2013. © 2013 Society of Plastics Engineers     

温敏聚N-异丙基丙烯酰胺的载药和释药性能研究

以对乙酰氨基酚为模型药物分子,温敏水凝胶聚N-异丙基丙烯酰胺(PNIPAAm)为载体,研究了药物在凝胶上的负载和在不同温度(25和37℃)下磷酸盐缓冲溶液(pH 7.4)中的释放行为.结果表明,对乙酰氨基酚的负载量约为35wt％,并且与载体PNIPAAm存在氢键作用.药物在磷酸盐缓冲溶液中的体外模拟释放结果显示,当温度(37℃)高于凝胶的LCST时,对乙酰氨基酚释放的较慢;当温度(25℃)低于其LCST时,释放的较快.因此,可通过环境温度的改变达到APAP在载体PNIPAAm上控制释放的目的.     

自交联法合成相转变温度范围窄的聚(N-异丙基丙烯酰胺)水凝胶微球

在不使用交联剂的情况下,采用无皂乳液聚合法合成自交联聚(N-异丙基丙烯酰胺)(PNIPAM)水凝胶微球。固体13C NMR分析结果表明,PNIPAM水凝胶微球中存在因链转移反应形成的自交联点。自交联PNIPAM水凝胶微球的相转变温度范围很窄,接近非连续体积相转变行为。合成过程中反应温度、反应时间、引发剂用量对微球粒径和溶胀比有比较明显的影响,这些因素对微球的相转变温度及其范围的影响均很小。     

Atomistic insights into solvation dynamics and conformational transformation in thermo-sensitive and non-thermo-sensitive oligomers

Solvation dynamics and conformational transformation in oligomers with varying degree of temperature sensitivity is studied using molecular dynamics (MD) simulations. Conformational transformation in three model systems namely poly(N-isopropylacrylamide) (PNIPAM), poly(acrylamide) (PAA), and poly(ethylene glycol) (PEG) are compared and contrasted to understand the origin of a coil-to-globule transformations across the lower critical solution temperature (LCST) in thermo-sensitive oligomers. PNIPAM, PAA, and PEG are water-soluble oligomers. However, for the temperature range used in these simulations, PNIPAM shows an LCST whereas PAA and PEG are non-thermo-sensitive. Oligomers of PNIPAM, PAA, and PEG consisting of 30 monomer units (30-mer) each were simulated at 5 °C (278 K) and 37 °C (310 K). Conformational transformations in the oligomers are evaluated using structural and dynamical correlation functions such as radius of gyration, radial distribution function, residence time probabilities and hydrogen-bonding life-times. Our simulations suggest that the solubility, solvation dynamics, and conformation of the oligomers are dictated by two factors: (a) the local structure of proximal water and (b) the diffusion and exchange kinetics of proximal water with bulk water. In thermo-sensitive oligomer such as PNIPAM, we find that the coil-to-globule transition is closely related to the local ordering and solvation dynamics of PNIPAM. We have identified stable configurations of proximal water molecules for an oligomer undergoing conformational transition. The slow diffusional properties of proximal water molecules near PNIPAM oligomers suggests that water forms a stable network near hydrophilic groups of PNIPAM as compared to the hydrophilic groups of PAA and PEG. Thermal perturbation of this solvated structure results in significant reduction in local ordering of water, which contributes to the globular collapse and the reduced solubility of PNIPAM above its LCST. On the other hand, non-thermo-sensitive oligomers such as PAA and PEG are characterized by much faster diffusion and exchange kinetics of proximal water at the two simulated temperatures compared to PNIPAM. This faster exchange kinetics helps in maintaining higher hydration level of the oligomers and is responsible for the apparent hydrophilic character and thereby the observed solubility at the two simulated temperatures.     

POEGMA hydrogel cross-linked by starch-based microspheres: synthesis and characterization

Hydrogels with high mechanical strength and controllable stimuli responses are highly desirable in the biomedical field. Herein, starch-based microspheres were used as macrosized cross-linkers to synthesize a series of extremely tough and thermosensitive poly[2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methyl ether methacrylate] (POEGMA) hydrogels. Scanning electron microscopy and confocal laser scanning microscopy showed that the starch-based microspheres were uniformly distributed in the hydrogel network. Compression test results indicated that the POEGMA hydrogel exhibits strength of 3.0 MPa, which is ten times greater than that of conventional hydrogels cross-linked using small molecules. This improvement in mechanical strength is attributable to the even distribution of the cross-linking points in the hydrogel, because of which the length of the flexible polymer chains between the microspheres was similar. As a result, the polymer network can readily dissipate stress. Moreover, the mechanical strength of the POEGMA hydrogel can be regulated efficiently by varying the amount of microspheres used. In addition, the POEGMA hydrogel exhibited a lower critical solution temperature (LCST) of 37°C when the 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA)/oligo(ethylene glycol) methyl ether methacrylate (OEGMA₃₀₀) mass ratio was 70/30. Further, the LCST of the POEGMA hydrogel can also be adjusted by adding salt or ethanol. The LCST decreased in the presence of sodium chloride but increased in the presence of ethanol.     

Hydroxyl end-functionalized poly(2-isopropyl oxazoline)s used as nano-sized colloidal templates for preparation of hollow polymeric nanocapsules

Hollow polymeric nanocapsules with a thermosensitive membrane are prepared and characterized. They reversibly change their dimensions during temperature variations below and above the transition of the membrane. The nanocapsules were prepared by three steps: (i) well-defined mesoglobules prepared from an LCST polymer (hydroxyl end functionalized poly(2-isopropyl-2-oxazoline), PiPOZ-OH) were coated with a thermo-sensitive cross-linked shell formed via seeded radical copolymerization of N-isopropylacrylamide (NIPAM) and N,N′-bis-methylene acrylamide to produce core–shell nanoparticles (ii), which were subjected to extensive dialysis below the LCSTs of both the core-forming PiPOZ-OH and shell-forming PNIPAM to remove the core (iii). The use of a core-forming polymer of low molecular weight (<8900 g mol⁻¹), narrow dispersity (<1.15) and relatively low T_g (52–68 °C) is beneficial as far as the effectiveness of the removal of the cores is concerned. The inherent immiscibility between PiPOZ-OH and PNIPAM as well as the specific raspberry-like structure of the core–shell particles also contributed for enhancement of the core removal effectiveness.     

Swelling and mechanical behavior of poly(N-isopropylacrylamide)/Na-montmorillonite layered silicates composite gels

Clay-polymer hydrogel composites have been synthesized based on poly(N-isopropylacrylamide) (PNIPAM) gels containing 0.25-4 wt% of the expandable smectic clay Na-montmorillonite layered silicates (Na-MLS). The morphology of the composite gels has been studied using a polarized optical microscope. The size of Na-MLS aggregates increases with Na-MLS concentration. The swelling ratio of the Na-MLS/PNIPAM composite in water is increased at the low Na-MLS concentration but decreases as the concentration increases. Correspondingly, the shear modulus of the gel is found to exhibit a distinct minimum against clay concentration. For Na-MLS concentrations ranging from 2.0 to 3.2 wt%, the composite gels have larger swelling ratio and stronger mechanical strength than those for a pure PNIPAM. The presence of Na-MLS does not affect the value of the lower critical solution temperature (LCST) of the PNIPAM. However, the gel volume change at the LCST is first increased and then decreased upon the increase of the Na-MLS. No pH induced phase transition is observed for the Na-MLS/PNIPAM composites. The experimental results can be explained by considering that Na-MLS is physically entrapped inside rather than chemically bonded into the gel.     

近红外光响应氧化石墨烯/微凝胶复合智能水凝胶

设计合成了一种包含氧化石墨烯（GO）片层、聚（N-异丙基丙烯酰胺）（PNIPAM）微凝胶球体和PNIPAM链段的复合结构水凝胶。通过控制聚合时间得到负载双键且粒径不同的PNIPAM微凝胶,将其作为交联点与N-异丙基丙烯酰胺（NIPAM）聚合,GO作为纳米填料掺入水凝胶体系,GO片层上的含氧基团与NIPAM上的胺基产生氢键物理交联。此方法制备的复合水凝胶同时具有温度敏感和近红外光敏感特性,通过改变GO浓度、微凝胶的合成时间、NIPAM浓度等条件,水凝胶的光敏感性和温度敏感性得到提升。相比于传统PNIPAM水凝胶,此种复合水凝胶能够对光响应,实现非接触式控制形变,且响应速率快、响应程度高,可应用于光控开关等领域。     

Synthesis and tunable thermoresponsive solution morphologies of 2,2‐bis‐methylolpropionic acid dendron–azobenzene–poly(N‐isopropyl acrylamide) copolymers

Amphiphilic temperature‐ and photoresponsive linear–dendritic block copolymers comprising second‐generation acetonide‐2,2‐bis‐methylolpropionic acid‐based polyester dendron and linear poly(N‐isopropyl acrylamide) (PNIPAM) linked by an azobenzene unit were synthesized using atom transfer radical polymerization (ATRP) followed by click chemistry. Linear PNIPAM precursor was prepared from an azide‐functionalized azobenzene containing ATRP initiator. Two polymers obtained by varying the chain length of the PNIPAM block showed different morphologies and lower critical solution temperature (LCST) values in aqueous solution. Complete change in morphology of the two polymers into large spherical aggregates and nanotubes, respectively, was observed upon heating the micellar solution above LCST. The azobenzene unit was found to undergo trans–cis photoisomerization in the assemblies and caused a change in the microenvironment of an encapsulated hydrophobic dye without any release. Acetonide groups on the dendron were deprotected to afford hydroxylated polymer that showed well‐defined morphologies above the LCST and after heating–cooling cycle while significant dye encapsulation was seen only above the LCST. © 2017 Society of Chemical Industry     

Preparation and Characterization of Temperature‐Sensitive Poly(Styrene‐Butadiene‐Styrene)/Poly(N‐Isopropylacrylamide) Hydrogel Elastomer with Interpenetrating Polymeric Networks

A poly(styrene‐butadiene‐styrene)/poly(N‐isopropylacrylamide) (SBS/PNIPAM) hydrogel elastomer with interpenetrating polymeric network structure is prepared by using solution free radical polymerization in benzene/tetrahydrofuran solvent mixture. The characterizations of hydrogel elastomers are investigated by Fourier transform infrared spectroscopy, scanning electron microscope, rheology, equilibrium swelling studies, and oscillatory swelling study. Results show that these hydrogel elastomers exhibit a temperature‐sensitivity inherited from PNIPAM component at the temperature around 30 °C. Besides, change with tetrahydrofuran to different proportion in solvent mixtures, constituent, and properties as gel content, swelling capacity, mechanical strength and volume phase transition degree are affected deeply.     

温敏性萃取水凝胶对生物大分子的分离

合成了均聚的聚N 异丙基丙烯酰胺(PNIPAM)水凝胶以及N 异丙基丙烯酰胺与丙烯酰胺共聚的〔P(NIPAM-AM)〕水凝胶,并研究了它们的溶胀性能及其对生物大分子的萃取分离性能。结果表明,两种温敏凝胶具有很好的溶胀性能,其低临界共溶温度(LCST)分别为30 4和31 0℃,它们对蛋白质和酶的分离效率在LCST附近发生突跃,如PNIPAM水凝胶对白蛋白的分离效率在LCST前后从96 2%降至59 8%。当交联剂N,N 次甲基双丙烯酰胺(Bis)的质量分数w(Bis)>4%时,分离效率大于90%(LCST以下)。     

温度敏感高分子水凝胶的合成及性能研究

从分子设计的角度出发,选用具有优良温敏性的N-异丙基丙烯酰胺(NIPA)为基本原料,制备了温度敏感水凝胶,系统研究了水凝胶的基本物理性能(密度、平均分子量、交联密度、平衡态水含量、固定电荷密度等),测试了水凝胶在不同离子强度下的溶胀、退溶胀性能,并对其响应机理进行了探讨,同时对水凝胶的机械性能进行了测试.结果表明:温度敏感水凝胶的溶胀受离子强度和温度的影响很大,离子强度越高,溶胀率越低;其机械强度随温度变化显著.     

A Composite Thermo‐Responsive Membrane System for Improved Controlled‐Release

A novel composite thermo‐responsive membrane system for improved controlled‐release is successfully developed. The membrane is composed of a porous membrane with grafted poly(N‐isopropylacrylamide) (PNIPAM) gates acting as functional valves, and a cross‐linked PNIPAM hydrogel inside the reservoir acting as the solute carrier. The thermo‐responsive controlled‐release characteristics of the proposed system are studied when the ambient temperature is continuously increased from 20 to 45 °C (across the LCST of PNIPAM) at a constant rate of 1.5 °C/min. The experimental results show that the prepared system exhibits significantly better performance for thermo‐responsive controlled‐release than single‐functional systems currently in existence, due to the cooperative action of the gating membrane and the inner cross‐linked hydrogel. Furthermore, due to the distinctive composite architecture, the proposed system can overcome some inherent disadvantages of current systems, such as the drug security problem of the reservoir‐type systems and the mechanical strength problem of the hydrogel matrix‐type systems. The system proposed in this study provides a new mode for thermo‐responsive controlled‐release.     

Structural effect of a series of block copolymers consisting of poly(N-isopropylacrylamide) and poly(N-hydroxyethylacrylamide) on thermoresponsive behavior

Well-defined diblock and triblock copolymers consisting of poly(N-isopropylacrylamide) (PNIPAM) and poly(N-hydroxyethylacrylamide) (PHEAA) were prepared using the atom transfer radical polymerization (ATRP) method. The number-average molecular weight and fraction of each segment were precisely controllable by adjusting the monomer/initiator ratio in feed. The lower critical solution temperature (LCST) of a series of block copolymers with different compositions was examined using a turbidimetry analysis. The copolymers with a relatively lower molar fraction of HEAA units in the polymer chain exhibited phase transition phenomenon, in which the LCST depended on the fraction in the copolymer. On the other hand, the LCST disappeared for the copolymers with higher HEAA unit molar fractions. The ¹H NMR measurement clarified that the disappearance of the LCST was attributed to the formation of the water-soluble micelle. Furthermore, the thermoresponsive property of the series of block copolymers was elucidated on the basis of the structural effect of the copolymer, which includes the order and length of the block segments.