Temperature-sensitive polyamidoamine dendrimer/poly(N-isopropylacrylamide) hydrogels with improved responsive properties

Novel temperature-sensitive poly(N-isopropylacrylamide)/amine-terminated polyamidoamine dendrimer G6-NH2 hydrogels with fast responsive properties were synthesized by forming semi-interpenetrating polymeric networks. In contrast to the conventional PNIPA hydrogel, these new gels showed rapid shrinking rate at the temperature above lower critical solution temperature (LCST), and exhibited higher equilibrium swelling ratio at room temperature. All these properties might be attributed to the incorporation of polyamidoamine dendrimer G6-NH2, which forms water-releasing channels and increases the hydrophilicity of PNIPA network. The novel hydrogels have potential applications in drug and gene delivery.     

Thermally Responsive Hydrogel Blends: A General Drug Carrier Model for Controlled Drug Release

Thermally responsive hydrogels have drawn significant research attention recently because of their simple use as drug carrier at human body temperature. Here we design a hybrid hydrogel that incorporates a hydrophilic polymer, polyethyleneimine (PEI), into the thermally responsive hydrogel poly(N‐isopropylacrylamide) (PNIPAm), as a general drug carrier model for controlled drug release. In this work, on one hand, PEI modifies the structure and the size of the pores in the PNIPAm hydrogel. On the other hand, PEI plays an important role in tuning the water content in the hydrogel and controls the water release rate of the hydrogel below the lower critical solution temperature (LCST), resulting in a tunable release rate of the drugs at human body temperature (37 °C). Different release rates are shown as different amounts of PEI are incorporated. PEI controls the release rate, dependent on the charge characteristics of the drugs. The hydrogel blends described in this work extend the concept of a general drug carrier for loading both positively and negatively charged drugs, as well as the controlled release effect.     

基于聚N-异丙基丙烯酰胺的细胞智能分离材料

聚 N -异丙基丙烯酰胺(PNIPAm)在水中是具有温度响应性的智能高分子材料,可用于细胞培养和自动脱附。本文从材料的制备方法出发,介绍了电子束照射接枝、等离子体处理接枝、表面活性自由基聚合、水凝胶等方法制备的材料对细胞培养及脱附的影响;阐述了细胞的脱附机理;讨论了加快细胞脱附的方法,包括共聚改性PNIPAm、PNIPAm接枝多孔膜、聚乙二醇(PEG)共聚PNIPAm接枝多孔膜、聚偏氟乙烯(PVDF)膜辅助细胞转移。从PNIPAm温敏性材料表面智能分离得到的细胞片因结构完整并保留了细胞外基质成分,在组织修复中得到了应用。     

含金刚烷基的N-异丙基丙烯酰胺共聚物水凝胶的制备和性能研究

合成了含金刚烷基的甲基丙烯酸金刚烷酯(AdMA)疏水单体,并通过与N-异丙基丙烯酰胺(NIPAM)共聚,制备了温敏性的(P(NIPAM-co-AdMA))共聚物水凝胶.用傅里叶变换红外光谱仪(FTIR)表征了凝胶的化学结构,用环境扫描电镜(ESEM)对凝胶断层结构的形貌进行了观察,用DSC测试了凝胶的体积相转变温度(LCST),并研究了共聚水凝胶的溶胀性能.结果表明,共聚物水凝胶的LCST能够高效地通过改变疏水单体的含量来调节,在实验所考察的范围内,LCST随AdMA含量的增加而线性降低;疏水单体的含量对凝胶的孔洞结构和溶胀性能存在一最优值,在最优的单体配比下,水凝胶具有均匀规整的大孔结构和超快的响应速率.如疏水单体含量为3%(AdMA∶NIPAM=3%)的共聚物水凝胶具有如渔网般均匀的多孔结构,当发生去溶胀时,在5min内就可以失去92%的水,不到10min的时间就可以完全达到去溶胀平衡,水保留率在4%以下.     

EuF3 纳米晶/PNIPAm复合水凝胶的制备及荧光温敏性能

以十一烯酸为表面活性剂, 采用液体-固体-溶液法(LSS)制备了EuF3纳米晶; 将其用CCl4处理, 得到表面修饰有C-Cl基团的功能化EuF3纳米晶; 通过原子转移自由基聚合(ATRP)制备EuF3 /聚N-异丙基丙烯酰胺(EuF3/PNIPAm)复合温敏水凝胶. 采用HRTEM, XRD, FTIR, DSC及PL等对EuF3 纳米晶及EuF3/ PNIPAm 复合凝胶的微观结构与性能进行了表征, 用变温荧光光谱研究了环境温度对复合凝胶荧光性能的影响. 结果表明, EuF3纳米晶呈六方相晶型; 粒径呈多分散分布, 且相对集中于10, 20和50 nm. 该复合凝胶的较低临界溶解温度(LCST)随纳米晶含量的增加而下降, 环境温度与纳米晶含量对复合凝胶的荧光特性产生明显影响.     

Autonomously-triggered microfluidic cooling using thermo-responsive hydrogels

We present autonomously-triggered on-chip microfluidic cooling devices that utilize thermo-responsive hydrogels to adapt to local environmental temperatures. An external rotating magnetic stirrer couples with an in situ fabricated nickel impeller in these centrifugal-based microfluidic cooling devices to recirculate cooler water. Temperature-responsive hydrogels, which exhibit volumetric expansion and contraction, are integrated at the axle of the impeller. In this design, the hydrogels behave similar to an automotive clutch, to autonomously control the impeller's rotation as a function of the local environmental temperature. Therefore, the hydrogels act as both sensors and actuators and help take away the necessity for additional temperature sensing, feedback, and/or control units here. Cooling devices capable of on-chip thermal management at multiple predetermined onset operation points are realized by changes to the composition of hydrogel to alter its lowest critical solution temperature (LCST). Furthermore, the effect of magnetic stirrer frequency on the fluid cooling and flowrates for different two-blade nickel impeller designs are presented.     

Frontal polymerization synthesis and drug delivery behavior of thermo-responsive poly(N-isopropylacrylamide) hydrogel

Thermo-responsive hydrogels of poly(N-isopropylacrylamide) (PNIPAm) were prepared by fontal polymerization and investigated as a temperature-triggered delivery device for the model drug aspirin. The influence of relative amount of reactant components on the feature of the polymerization front was studied. Furthermore, aspirin was loaded into hydrogels prepared by fontal polymerization method and classical polymerization, respectively, and its release characteristics were determined under different temperature conditions (25 °C and 37 °C). The drug storages and kinetic parameters for two hydrogels indicated that drug-loading capacity and drug release of frontal polymerization (FP) hydrogel were improved as compared with the classical polymerization (CP) one. Scanning electronic microscope and differential scanning calorimetry (DSC) results could account for these improvements in drug delivery for FP hydrogel. The above results indicate that FP can be an alternative method for the preparation of PNIPAm hydrogels used as drug delivery devices with less time consuming and easier protocols.     

Porous alginate-Ca hydrogels interpenetrated with PNIPAAm networks: Interrelationship between compressive stress and pore morphology

Thermo-sensitive porous hydrogels composed of interpenetrated networks (IPN) of alginate-Ca²⁺ and PNIPAAm have been obtained. The hydrogels were prepared by cross-linking alginate-Na⁺ with Ca²⁺ ions inside PNIPAAm networks. Compressive tests and scanning electron microscopy were used to evaluate gel strength and pore morphology, respectively. IPN hydrogels displayed two distinct pore morphologies under thermal stimuli. Below 30-35 °C, the LCST of PNIPAAm in water, IPN hydrogels were highly porous. The pore size of hydrogel heated above LCST became progressively smaller. Alginate-Ca²⁺ and PNIPAAm hydrogels, used as references, did not present such behaviour, indicating that the porous effect is due to IPN hydrogel. It was verified that higher strength is achieved when the hydrogel presents small pore size and the temperature is increased. It is suggested that at temperatures above LCST, the PNIPAAm chains shrink and pull the alginate-Ca²⁺ networks back. During shrinking, the polymer chains occupy the open spaces (pores from which water is expelled), and therefore, the hydrogel becomes less deformable when subjected to compressive stress. The results presented in this work indicate that the mechanical properties as well as the pore morphologies of these IPN hydrogels can be tailored by thermal stimulus.     

Recognition‐Mediated Hydrogel Swelling Controlled by Interaction with a Negative Thermoresponsive LCST Polymer

Most polymeric thermoresponsive hydrogels contract upon heating beyond the lower critical solution temperature (LCST) of the polymers used. Herein, we report a supramolecular hydrogel system that shows the opposite temperature dependence. When the non‐thermosesponsive hydrogel NaphtGel, containing dialkoxynaphthalene guest molecules, becomes complexed with the tetra cationic macrocyclic host CBPQT⁴⁺, swelling occurred as a result of host–guest complex formation leading to charge repulsion between the host units, as well as an osmotic contribution of chloride counter‐ions embedded in the network. The immersion of NaphtGel in a solution of poly(N‐isopropylacrylamide) with tetrathiafulvalene (TTF) end groups complexed with CBPQT⁴⁺ induced positive thermoresponsive behaviour. The LCST‐induced dethreading of the polymer‐based pseudorotaxane upon heating led to transfer of the CBPQT⁴⁺ host and a concomitant swelling of NaphtGel. Subsequent cooling led to reformation of the TTF‐based host–guest complexes in solution and contraction of the hydrogel.     

纤维素纳米纤维接枝聚(N-异丙基丙烯酰胺)水凝胶的制备与表征

将具有温度响应的聚N-异丙基丙烯酰胺(PNIPAm)接枝到电纺纤维素纳米纤维膜上,制备温度响应型纤维素接枝聚N-异丙基丙烯酰胺(PNIPAm-g-Cell)纳米纤维水凝胶。 研究接枝单体(N)与纤维素(c)的质量比、反应温度、反应时间和引发剂浓度对产物接枝率、溶胀性和形貌的影响。 结果表明,最佳聚合反应条件为m(N):m(c)=15:1、反应温度40 ℃、反应时间3 h、引发剂浓度为10 mmol/L,得到PNIPAm-g-Cell接枝率和溶胀率分别为35%和31%。 与PNIPAm相比,PNIPAm-g-Cell水凝胶的低临界相转变温度(LCST)显著升高,说明亲水性纤维素的引入改变了体系的亲疏水平衡。 去溶胀动力学测试表明,0.5 min内接枝率为25%和35%的水凝胶保水率分别降低至93%和61%。 说明接枝率越高PNIPAm-g-Cell水凝胶对温度的响应速度越快,对温度越敏感。     

新型pH及温度敏感性水凝胶

水凝胶是由三维交联网络结构的高聚物和介质共同组成的多元体系 ,因其独特的刺激响应行为 ,已在药物释放体系、物料分离、化学机械、人工肌肉等领域显示了良好的应用前景[1,2 ] .在人体体液这种复杂的环境中 ,水凝胶同时受到ｐＨ和温度等多重刺激作用 ,因此 ,研究多重响应性水凝胶具有重要意义 .聚氨酯作为一种广泛应用的高分子材料具有结构易调节、力学性能优异及生物相容性好等特点 ,在生物医学领域可将其用作假肢部件、外科用置入管、隐形眼睛等 .已有文献报道了ｐＨ敏感性聚氨酯水凝胶[3～ 5] ,但对多重响应性聚氨酯基水凝胶的报道还很…     

Chemically Crosslinked pH- and Temperature-Sensitive (N-isopropylacrylamide-co-1-vinyl-2-pyrrolidone) Based on New Crosslinker: I. Swelling Behavior

Novel pH- and temperature-sensitive polymer matrices based on N-isopropylacrylamide have been developed. The hydrogels were prepared by bulk radical polymerization of N-isopropylacrylamide and 1-vinyl-2-pyrrolidinone in appropriate amounts of distilled water using different mol% of traditional N,N-methylene bisacrylamide (MBA) and the new synthesized N,N,N-tris acryloyl melamine (MAAm) crosslinkers. Lower critical solution transition temperatures (LCST) were measured by differential scanning calorimetry. The synthesized hydrogels have LCST lower than 40°C. The influence of environmental conditions such as temperature and pH on the swelling behavior of these polymeric gels was investigated. The swelling behaviors of the resulting gels show pH sensitivity. The crosslinked NIPAAm/VP with MAAm hydrogels exhibited more rapid deswelling rate than NIPAAm/VP hydrogels crosslinked with MBA in pure water in response to abrupt temperature changes from 20°C to 50°C.     

Doubly responsive polymer-microgel composites: rheology and structure

Mixtures of alkali swellable microgels and linear PNIPAm chains exhibit doubly responsive properties both with pH and temperature. Below the lower critical solution temperature (LCST), the linear chains of PNIPAm are soluble and increase the osmotic pressure outside the microgels, which causes them to deswell. Above the LCST, the PNIPAm chains become insoluble and form spherical colloidal particles confined between the microgels that subsequently reswell. The swelling and deswelling of the microgels change the rheological properties of the composites, providing a unique way to tune the elasticity of the composites with temperature. The structure of the composites above the LCST is studied using multiple light scattering and fluorescence confocal microscopy. The phase separation of PNIPAm above the LCST is strongly affected by the confinement of the PNIPAm chains between the microgels.     

Thermoresponsive behavior of poly(n-isopropylacrylamide) hydrogels containing gold nanostructures

We report the changes in the structure and thermoresponsive behavior of poly(N-isopropylacrylamide) (PNIPAm) hydrogels when gold nanostructures are synthesized in situ within the hydrogel matrix. Cross-linked PNIPAm hydrogels were synthesized using NIPAm and 0.00-3.50% (w/w versus NIPAm) of N,N'-methylenebisacrylamide (MBAm) and/or N,N'-cystaminebisacrylamide (CBAm) as cross-linking agents. The hydrogels were soaked in potassium tetrachloroaurate to introduce gold ions. The hydrogels containing Au3+ were then immersed in a sodium borohydride solution to reduce the gold ions. Infrared spectroscopy, UV-visible spectroscopy, and equilibrium swelling were used to examine the structural/physical differences between gels of different compositions; UV-visible spectroscopy and mass measurements were used to observe the kinetics and thermodynamics of the hydrogel volume phase transition. These studies revealed several differences in the physical characteristics and thermoresponsive behavior of hydrogels based on cross-linker identity and the presence or absence of gold nanostructures. Hydrogels with gold nanostructures and high CBAm and low MBAm content have equilibrium swelling masses 3-20 times their native analogues. In comparison, gold-containing hydrogels with high MBAm and low CBAm content have swelling masses that are equal to their native analogues. Additionally, the gold-containing PNIPAm hydrogels cross-linked with only CBAm have a deswelling temperature of approximately 40 degrees C, approximately 8 degrees C above the samples cross-linked with only MBAm. Varying the CBAm content and introducing gold enables tuning of the deswelling temperature.     

Monitoring mesoglobules formation in PNIPAm solutions using Nile Red solvatochromism

Nile Red solvatochromism is used to monitor phase separation in concentrated poly(N-isopropyl acrylamide) (PNIPAm) aqueous solutions. Below the lower critical solution temperature (LCST), Nile Red molecules are in a polar environment and thus exhibit negligible fluorescence. Above the LCST, the aggregation of the PNIPAm chains into hydrophobic mesoglobules provides a nonpolar environment, causing a strong increase of fluorescence. The spectra show two emission bands, which can be related to the partitioning of Nile Red molecules between the core and the surface of the mesoglobules. More generally, the technique appears as a new and promising tool to probe microheterogeneities in polymer solutions or mixtures.     

An efficient method for the fabrication of temperature-sensitive hydrogel microactuators

In this article a new method for the photolithographical deposition of temperature-sensitive hydrogels is presented. The method can be used in conjunction with standard 365 nm UV-photolithography to accurately dimension and position temperature-sensitive hydrogel microactuators in a highly parallel fashion. A number of characteristics of the hydrogels were investigated. These include: the photolithographical reproduction quality, the effect of the crosslinking density in the hydrogels on their swelling behavior, the swelling hysteresis behavior, the effect of dimensional constraints on the swelling of the hydrogels and the effect of copolymerization with an ionizable comonomer on the temperature behavior of the hydrogels. The method presents a considerable improvement in the microfabrication of temperature-sensitive hydrogel microactuators and has potential for the mass-fabrication of these interesting microactuators.     

Synthesis and release profile analysis of thermo-sensitive albumin hydrogels

Novel thermo-responsive hydrophilic microspheres were prepared by free radical polymerization of methacrylate bovine serum albumin and N-isopropylacrylamide, as cross-linker and functional monomer, respectively. The incorporation of monomers in the network was confirmed by infrared spectroscopy, while the network density and shape of hydrogels strictly depend on concentration of monomers in the polymerization feed. The thermal analyses showed negative thermo-responsive behavior with pronounced water affinity of microspheres at temperature lower than lower critical solution temperature (LCST). The in vitro release studies of drug-loaded thermo-sensitive hydrogels were performed. Experimental data showed, for the copolymers with functional monomer/cross-linker ratio ≤ 1, a predominant drug release in the collapsed state, while the copolymers with functional monomer/cross-linker ratio > 1 showed prominent drug release in the swollen state. Below the hydrogel LCST, drug release through the swollen polymeric networks was observed, while a squeezing-out effect at temperature above the LCST was predominant.     

Influence of crosslinker and ionic comonomer concentration on glass transition and demixing/mixing transition of copolymers poly(N-isopropylacrylamide) and poly(sodium acrylate) hydrogels

Hydrogels based on N-isopropylacrylamide and sodium acrylate as ionic comonomer were synthesized by free radical polymerization in water using N,N′-methylenebisacrylamide as crosslinker and ammonium persulfate as initiator. The glass transition of dried copolymers poly(N-isopropylacrylamide) (PNIPA) and poly(sodium acrylate) (SA) gels and demixing/mixing transition of PNIPA-SA hydrogels swollen with increasing amounts of water were studied using conventional differential scanning calorimetry. In the crosslinked polymers, the glass transition linearly increases, and the transition range becomes broader, with increasing crosslinker content. Increasing content of ionic comonomer also produces an increase of glass transition temperature, which moves to higher temperatures with higher sodium acrylate fraction. The influence of chemical structure of PNIPA-SA hydrogels on the lower critical solution temperature (LCST) of PNIPA-SA/water mixtures during heating and cooling was quantified as function of the content of the crosslinker and the ionic comonomer, as well as water content of the hydrogel in the range from 95 to 70 wt%. At parity of water content, the LCST occurs at higher temperatures for gels containing higher amounts of sodium acrylate. Similarly, the introduction of N,N′-methylenebisacrylamide causes an increase of the LCST, which grows with increasing of crosslinking degree of the hydrogel.     

Injectable Graphene Oxide/Graphene Composite Supramolecular Hydrogel for Delivery of Anti-Cancer Drugs

Injectable hydrogels have attracted a lot of attention in drug delivery, however, their capacity to deliver water-insoluble or hydrophobic anti-cancer drugs is limited. Here, we developed injectable graphene oxide/graphene composite supramolecular hydrogels to deliver anti-cancer drugs. Pluronic F-127 was used to stabilize graphene oxide (GO) and reduced graphene oxide (RGO) in solution, which was mixed with α-cyclodextrin (α-CD) solution to form hydrogels. Native hydrogel was used as control. GO or RGO slightly shortened gelation time. The storage and loss moduli of the hydrogels were tracked by dynamic force measurement. The storage modulus of GO or RGO composite hydrogels was larger than that of the native hydrogel. Hydrogels were unstable in solution and eroded gradually. GO or RGO in Pluronic F-127 solution could potentially improve the solubility of the water-insoluble anti-cancer drug camptothecin (CPT), especially with large drug-loaded CPT amount. Drug release behaviors from solutions and hydrogels were characterized. The nanocomponents (GO or RGO) were able to bind more drug molecules either for CPT or for doxorubicin hydrochloride (DXR) in solution. Therefore, GO or RGO composite hydrogel could potentially enable better controlled and gentler drug release (for both CPT and DXR) than native hydrogel.     

Synthesis and characteristic of the thermo- and pH-sensitive hydrogel and microporous hydrogel induced by the NP-10 aqueous two-phase system

A series of novel thermo- and pH-sensitive (NP10-AA TPS) hydrogels and microporous (NP10-AA MP) hydrogels, inducing by polyoxyethylene (10) nonyl phenyl ether (NP-10) aqueous two-phase system, was designed and fabricated with acrylic acid (AA) as the monomer for the first time. The resultant NP10-AA TPS hydrogel, compared with the traditional TPS hydrogel, was more advanced in both of the high swelling ratio and the variable lower critical solution temperature (LCST). A simple synthesis technique of the NP10-AA MP hydrogel was developed. The thermo-sensitivity of the NP10-AA TPS hydrogel including the initial swelling ratio, LCST, dehydrated efficiency, was depended strongly on the crosslinker (MBA), initiator (APS), NP-10 and AA concentration. The swelling rate of the NP10-AA MP hydrogel was much higher than that of AA hydrogel dehydrated in the same lyophilization condition.