Novel gelatin-polyoxometalate based self-assembled pH responsive hydrogels: formulation and in vitro characterization

The purpose of the study was to develop physically cross-linked novel pH-responsive gelatin – Wells–Dawson-type polyoxometalate (POM)-based self-assembled hydrogels using acrylic acid as a pH-responsive monomer. Cross-linking was achieved through electrostatic interactions between the cationic polymer and anionic Wells–Dawson POM [P₂W₁₅O₅₆]^12?. Ammonium persulfate and sodium hydrogen sulfite were used as initiators. The hydrogels were yellowish in color and exhibited low mechanical strength. Swelling, drug release, and pH sensitivity studies were conducted at pH 1.2 and 7.4. pH-dependent swelling and release of [P₂W₁₅O₅₆]^12? from the prepared hydrogels were observed, with a maximum at pH 7.4. The hydrogels were characterized by thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy, and Fourier transform infrared spectroscopy for evaluation of the surface morphology, hydrogel confirmation, and thermal properties. The results obtained confirmed the development of a gelatin–POM-based self-assembled hydrogel. It can be concluded that as a result of successful physical cross linking, the prepared hydrogels possess desired characteristics of a drug delivery system and can hence be used for a controlled delivery of the encapsulated polyanions. .     

pH-响应型K5多糖药物传递系统的构建及应用

化学疗法是目前癌症治疗的主要方法,但目前常用的化疗药物却普遍存在水溶性不佳、缺乏选择性、毒副作用大等不足,而限制了其应用。本研究基于肝素前体K5多糖为模板,利用具有pH响应性的硼酸酯键,构建了K5-脱氧胆酸（K5AD）两亲性药物传递系统,用于阿霉素（doxorubicin,DOX）的靶向传递释放。考察了该体系的体外药物释放行为,并在体外评价其对肿瘤细胞的抑制作用。结果表明,K5AD的临界胶束浓度值为23.5mg/L,在水溶液中能自组装形成平均粒径为196.7nm的胶束;K5AD-DOX体外药物释放实验显示其具有pH-响应的释药行为,在pH 5.0的酸性环境下药物释放速率较pH 7.4下更快。细胞实验表明,K5AD-DOX对肿瘤细胞的毒性远大于对正常细胞的毒性,表现出治疗的选择性。     

Evaluation of various strategies to formation of pH responsive hydroquinone-terminated films on carbon electrodes

The hydroquinone/quinone (H₂Q/Q) redox system was tethered to glassy carbon surfaces using first an electrochemical pre-oxidation treatment to afford carboxylic acid functionalities followed by immobilizing the H₂Q precursor, n-(2,5-dimethoxyphenyl)alkan-1-amine (general structure: H₂N-(CH₂)_n-C₆H₃(OCH₃)₂, n = 1, 2, 4, 8, and 12), by carbodiimide chemistry and a final demethylation reaction. The resultant surfaces exhibited the expected chemical reversibility in aqueous solution with a pH-sensitive position of the formal potential (∼55 mV/pH unit), and an increase in the peak potential separation going from 0.02 V for n = 1 to 0.21 V for n = 12. The films were very robust and could withstand prolonged sonication and relatively large potential excursions. While the films followed the expected kinetic distance dependence for up to 4 methylene units the electrode kinetics was faster than expected for longer alkyl spacers. We suggest that film disorder, electrode-mediating effects, and a roughened electrode material could account for these apparent inconsistencies. To further understand such effects, two complementary electrode modification strategies leading to better film ordering on carbon were adapted; immobilizing a thin layer of benzoic acid by oxidative deposition of 4-aminobenzoic acid or employing a plasma deposition process to tether an acid analogue. Analysis of the various electrodes was accomplished by electrochemical methods, atomic force microscopy, and X-ray photoelectron spectroscopy.     

Temperature and pH responsive hydrogels based on polyethylene glycol analogues and poly(methacrylic acid) via click chemistry

A novel temperature responsive copolymer, poly[2‐(2‐methoxyethoxy)ethyl methacrylate‐co‐oligo(ethylene glycol)methacrylate‐co‐N‐hydroxymethyl acrylamide] [P(MEO₂MA‐co‐OEGMA‐co‐HMAM)], was synthesized by atom transfer radical polymerization. pH responsive poly(methacrylic acid) (PMAA) was synthesized by reversible addition‐fragmentation chain transfer polymerization. After the hydroxyl groups on P(MEO₂MA‐co‐OEGMA‐co‐HMAM) were transformed into azide groups and the carboxyl groups on PMAA were transformed into alkyne groups respectively, a novel temperature and pH responsive hydrogel was fabricated by click chemistry between the azide‐P(MEO₂MA‐co‐OEGMA‐co‐HMAM) and alkyne‐PMAA in the presence of CuSO₄ and sodium ascorbate in aqueous solution. The rheological kinetics of gel formation demonstrated that gelation had commenced within 5 min at 25 °C, since then the storage modulus (G′) was higher than the loss modulus (G″). SEM images of hydrogel morphology and the swelling ratios of hydrogel at different temperatures and pH proved that the formed hydrogel had temperature and pH sensitivities. Bovine serum albumin was used as a model to evaluate the sustained release of the hydrogel; the results indicated that the hydrogel was a promising candidate for controlling protein drug delivery. © 2015 Society of Chemical Industry     

基于多目标的模糊神经网络及在pH控制过程中的应用

设计了一种基于多目标的动态模糊递归神经网络（FRNN）建模方法,用于pH中和过程的广义预测控制。所设计的多目标优化算法以提高拟合精度和简化网络结构为原则,同时优化模糊神经网络中的模糊规则数、隶属度函数中心点及其宽度,由此得到的FRNN模型可以高精度拟合pH中和过程。依据该动态模型,在控制过程的每一个控制周期得到其局部线性模型,将广义预测控制中复杂的非线性优化问题转化为简单的二次线性规划问题。仿真对比结果验证了所提方法的有效性。     

Pole-placement self-tuning control of nonlinear Hammerstein system and its application to pH process control

By taking advantage of the separation characteristics of nonlinear gain and dynamic sector inside a Hammerstein model, a novel pole placement self tuning control scheme for nonlinear Hammerstein system was put forward based on the linear system pole placement self tuning control algorithm. And the nonlinear Hammerstein system pole placement self tuning control (NL-PP-STC) algorithm was presented in detail. The identification ability of its parameter estimation algorithm of NL-PP-STC was analyzed, which was always identifiable in closed loop. Two particular problems including the selection of poles and the on-line estimation of model parameters, which may be met in applications of NL-PP-STC to real process control, were discussed. The control simulation of a strong nonlinear pH neutralization process was carried out and good control performance was achieved.     

非线性Hammerstein模型预测控制策略及其在pH中和过程中的应用

所有实际工业过程都包含一定程度的非线性,如pH中和过程由于其本身的强非线性是工业过程控制中具有挑战性的难题,但至今为止仍缺乏有效的非线性控制方法。将基于差分方程模型的模型预测控制策略(model predictive control,MPC)推广到包含一个静态非线性多项式函数和一个线性差分方程动态环节的非线性Hammerstein系统,详细描述了基于静态非线性多项式函数的最优控制作用求解方法,提出了一套新的非线性Hammerstein MPC 控制策略(nonlinear Hammerstein predictive control,NLHPC)。pH中和过程控制仿真和控制实验表明,NLHPC的控制结果好于工业上常用的非线性 PID(nonlinear PID,NL-PID)控制器。     

Amphiphilic urethane acrylate hydrogels: pH sensitivity and drug‐releasing behaviors

Amphiphilic urethane acrylate hydrogels containing ionic groups (dimethylolpropionic acid, DMPA) were prepared with varying the molecular weight of the hydrophobic segment (polyether type, PTMG), and their swelling and drug‐releasing behaviors were examined. Amphiphilic property for the hydrogels could be confirmed by observing the swelling in both water and organic solvent (benzene) readily. High pH sensitivity was observed due to the carboxylic groups incorporated into the molecular backbone of the urethane acrylate molecules. Owing to the amphiphilic property, it was possible to load hydrophilic (riboflavin selected) and hydrophobic (indomethacin selected) drugs in the network with ease. Each drug successfully released from the network of the urethane acrylate. The releasing behaviors were dependent upon the swelling ones and followed Fickian diffusion. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 1305–1311, 1999     

A novel temperature and pH dual‐responsive hybrid hydrogel with polyhedral oligomeric silsesquioxane as crosslinker: synthesis,characterization and drug release properties

Octavinyl polyhedral oligomeric silsesquioxane (OVPS) is used as the crosslinker instead of N,N′‐methylenebisacrylamide (BIS) to copolymerize with 2‐(dimethylamino)ethyl methacrylate (DMAEMA) or DMAEMA and N‐isopropylacrylamide (NIPAM) to prepare hybrid hydrogels: P(OVPS‐co‐DMAEMA) and P(OVPS‐co‐DMAEMA‐co‐NIPAM). The prepared hydrogels are transparent and show dual response to temperature and pH. The hydrogels were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, dynamic mechanical analysis and tensile tests. Their mechanical properties, swelling ratio, deswelling and reswelling behaviors as well as drug release properties were investigated. The results indicate that OVPS can be incorporated into polymer networks in proportion to feed ratios. The P(OVPS‐co‐DMAEMA) hydrogel exhibits more homogeneous interior structure, higher swelling ratio and faster response than the conventional hydrogel prepared with BIS. Moreover, the incorporation of OVPS enhances the compression and tensile properties of the hydrogels. The feed ratios of OVPS and NIPAM have a great effect on volume phase transition temperature, thermal sensitivity, swelling behavior, mechanical properties and drug release properties of the hybrid hydrogels. The prepared dual‐responsive OVPS‐containing hydrogels are expected to be used as biomedical materials in drug release and tissue engineering. © 2014 Society of Chemical Industry     

Thermoresponsive poly (N-vinylcaprolactam)-g-galactosylated chitosan hydrogel: synthesis,characterization, and controlled release properties

Abstract

A dual (thermo- and pH-) responsive hybrid copolymer, poly(N-vinylcaprolactam) grafted galactosylated chitosan (PNVCL-g-GC) was synthesized by EDC/NHS crosslinking. PNVCL-g-GC exhibited a temperature-dependent phase change (LCST) at 32?°C in aqueous solutions. PNVCL-g-GC hydrogel scaffold was fabricated by freeze-drying, and evaluated as a delivery vehicle dependent on environmental pH and temperature. PNVCL-g-GC was characterized using ATR-FTIR, 1H-NMR, DSC, TGA, rheometry, and SEM. The swelling degree increased by the decrease both in temperature and pH. A faster BSA release was observed at 40?°C and at pH 7.2 from the cytocompatible and hemocompatible copolymer.     

Amphiphilic chitosan graft copolymer via combination of ROP, ATRP and click chemistry: Synthesis, self-assembly, thermosensitivity, fluorescence, and controlled drug release

Novel amphiphilic chitosan-g-poly(ε-caprolactone)-(g-poly(2-(2-methoxyethoxy)ethyl methacrylate)-co-oligo(ethylene glycol) methacrylate) (CS-g-PCL(-g-P(MEO₂MA-co-OEGMA))) copolymers with double side chains of PCL and P(MEO₂MA-co-OEGMA) were synthesized via combination of ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP) and click chemistry. The molar ratio of PCL and P(MEO₂MA-co-OEGMA) was varied through variation of the feed ratio and the coupling efficiency of click chemistry is comparatively high. The graft copolymers can assemble into spherical micelles. The micelles show thermosensitive properties and the lower critical solution temperatures (LCSTs) were influenced by CS chains and the ratio of PCL and P(MEO₂MA-co-OEGMA) side chains. Moreover, the micelles can reversibly swell and shrink in response to the change of temperatures. Furthermore, the micelles present obvious fluorescence and the fluorescent intensity can be adjusted by altering the temperatures. The investigation of doxorubicin release from the micelles indicated that the release rate of the drug could be effectively controlled by altering the temperatures.     

Toward efficient water/oil separation material: Effect of copolymer composition on pH‐responsive wettability and separation performance

Interest in functional soft matter with stimuli‐responsive wettability has increasingly intensified in recent years. From the chemical product engineering viewpoint, this study aims to fabricate reversible pH‐responsive polymeric surfaces with controllable wettability using [poly(2,2,3,4,4,4‐hexafluorobutyl methacrylate)‐block‐ poly(acrylic acid) (PHFBMA‐b‐PAA)] block copolymers. To attain this aim, three block copolymers with different PAA segment lengths were synthesized for the first time through Cu(0)‐mediated reversible‐deactivation radical polymerization and hydrolysis reaction. pH‐induced controllable wettability was achieved by spin‐coating the resulting block copolymers onto silicon wafers. Results showed that the pH‐responsive wetting behavior was introduced by incorporating the PAA block, and that the responsiveness of as‐fabricated surfaces was greatly influenced by PAA content. All three evolutions of water contact angle with pH shared a similar inflection point at pH 5.25. Furthermore, on the basis of the wetting properties and mechanism understanding, the application of copolymer coated meshes in layered water/oil separation was exploited. Given their superhydrophilicity and underwater superoleophobicity, PHFBMA₇₀‐b‐PAA₁₄₈ and PHFBMA₇₀‐b‐PAA₂₁₁ coated stainless steel meshes (SSMs) can efficiently separate water from different mixtures of organic solvent and water with high flux. However, considering long‐term use, the PHFBMA₇₀‐b‐PAA₁₄₈ coated SSM with good stability may be the best copolymer for water/oil separation. Therefore, a coordination of structure, composition, and functionality was necessary to enable practical applications of the functional materials. © 2016 American Institute of Chemical Engineers AIChE J, 62: 1758–1771, 2016     

Electrochemical properties of ferrocene modified polysiloxane/chitosan nanocomposite and its application to glucose sensor

A ferrocene functionalized polysiloxane was synthesized and its composite with chitosan was prepared. The electrochemical properties in solution and in immobilized states were examined for both the ferrocene functionalized polysiloxane and its composite with chitosan. The composite film exhibits a reversible redox wave at E°′ = +360 mV vs. Ag/AgCl which is 110 mV more negative than that of the ferrocene functionalized polysiloxane film. It can be explained by the introduction of chitosan to enhance the hydrophilicity of the film and increase mass transport rate in aqueous condition. The composite film shows a very facile electron transport behavior with an apparent diffusion coefficient of 3.5 × 10⁻⁶ cm²/s. The scanning electron microscopic analysis of the film, which is in dried state, reveals that the ferrocene polysiloxane forms average 500 nm size spheres and those are evenly distributed in the chitosan matrix to give a homogeneous nanocomposite. The significantly large value of the apparent diffusion coefficient of the ferrocene moieties in the composite film can be explained by the introduction of highly hydrophilic character to the film originated from the high water-uptake capability of chitosan to give solution-like behaviors of the film in solution. The composite is found to be a useful platform to host enzymes to make biosensors and glucose sensing capability is demonstrated.     

Computational Investigation of the pH Dependence of Stability of Melanosome Proteins: Implication for Melanosome formation and Disease

Intravesicular pH plays a crucial role in melanosome maturation and function. Melanosomal pH changes during maturation from very acidic in the early stages to neutral in late stages. Neutral pH is critical for providing optimal conditions for the rate-limiting, pH-sensitive melanin-synthesizing enzyme tyrosinase (TYR). This dramatic change in pH is thought to result from the activity of several proteins that control melanosomal pH. Here, we computationally investigated the pH-dependent stability of several melanosomal membrane proteins and compared them to the pH dependence of the stability of TYR. We confirmed that the pH optimum of TYR is neutral, and we also found that proteins that are negative regulators of melanosomal pH are predicted to function optimally at neutral pH. In contrast, positive pH regulators were predicted to have an acidic pH optimum. We propose a competitive mechanism among positive and negative regulators that results in pH equilibrium. Our findings are consistent with previous work that demonstrated a correlation between the pH optima of stability and activity, and they are consistent with the expected activity of positive and negative regulators of melanosomal pH. Furthermore, our data suggest that disease-causing variants impact the pH dependence of melanosomal proteins; this is particularly prominent for the OCA2 protein. In conclusion, melanosomal pH appears to affect the activity of multiple melanosomal proteins.     

Preparation and photophysical behaviors of fluorescent chitosan bearing fluorescein: Potential biomaterial as temperature/pH probes

A novel method for attaching fluorescein (via its epoxy derivative) to water‐soluble chitosan, and the temperature/pH‐sensitive qualities of fluorescence were investigated. 3‐Epoxypropoxy fluorescein (EPF) was firstly synthesized by the reaction between fluorescein and epichlorohydrin, and then water‐soluble chitosan bearing fluorescein (CS‐EPF) was prepared via ring‐opening reaction with EPF. They were characterized by the methods of ¹H NMR, MS, IR, UV–Vis, and luminescence spectra, respectively. The chemiluminescent and photophysical behaviors of EPF and CS‐EPF were studied in detail. The results showed that the fluorescent chitosan could still provide temperature and pH sensitivities similar to that of fluo‐ rescein, achieving better long‐term stability and fast equilibrium response. CS‐EPF had an excellent linear response between relative fluorescence intensity and temperature in the range of 0–60°C and two linear relationships between relative fluorescence intensity and pH in 0.0–4.14 and 8.15–13.20, respectively. This investigation may provide a convenient way to prepare low‐cost and multifunctional macromolecule biomaterial to probe pH and temperature in biological systems. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 3960–3966, 2007     

Complexation of chitosan and gelatin: From soluble complexes to colloidal gel

The formation of soluble and insoluble complexes between chitosan (CH) and gelatin type B (GB) was investigated as a function of pH (3.0–6.5), sodium chloride (NaCl) concentration (0–100 mM), and storage time (up to 40 days). The turbidity of the CH/GB complexes achieved a maximum value at pH 5.5 and increased with time. The increase of ionic strength first intensified the complex formation but then decreased it at higher salt content. After phase separation, the main component of the separated dense phase was water, from 95.5 to 97.8 wt%, depending on NaCl concentration. With increasing storage time, the insoluble phase changed from a liquid-like system to a thermoreversible colloidal gel, as supported by confocal laser scanning microscopy as well as rheological data. The formation of this colloidal gel is explained in terms of electrostatic complexation and hydrogen bonding.     

电镀废水处理pH测控的相关问题

为了保证电镀废水处理中pH测控的准确性,介绍了玻璃电极的结构及pH测量的原理,指出了玻璃电极的缺陷(如高输入阻抗、电极的污染与腐蚀)对pH测控的影响,给出了电极清洗及pH计校正的一般方法,提出了自动报警或投药装置在使用中应注意的问题。     

Synthesis of biodegradable pentaarmed star-block copolymers via an asymmetric BIS-TRIS core by combination of ROP and RAFT: From star architectures to double responsive micelles

Biodegradable star-shaped poly(?-caprolactone) and poly(?-caprolactone-b-l-lactide) (5sPCL-b-PLLA) with five arms were synthesized by ring-opening polymerization (ROP) from an asymmetric BIS-TRIS core via “core-first” strategy. Subsequently, a series of amphiphilic and double responsive star-block copolymers were synthesized by Z-RAFT star polymerization of N,N-dimethylamino-2-ethyl methacrylate (DMAEMA) from the star-shaped macro-RAFT agent, which was prepared by attaching 3-benzylsulfanylthiocarbonylthiocarbonylsufanylpropionic acid (BSPA) to 5sPCL-b-PLLA using a simple two-step reaction sequence. GPC and ¹H NMR data demonstrated the polymerization courses are under control. The molecular weight of 5sPCL-b-PLLA-b-DMAEMA increased with the monomer conversion, and the molecular weight distribution was in the range of 1.19-1.37. The spherical micelles with degradable core and pH/thermo-double sensitive shell had been prepared from the aqueous medium of the amphiphilic star-shaped copolymers by dialysis method. Both pH and thermal-responsive behaviours of copolymer micelles obtained in this study were investigated. The micelle size and morphology were measured by DLS, AFM and TEM.     

Influence of lignin's pH on polyurethane flexible foam formation and how to control it

Low pH of commercial lignins has a catastrophic impact on the polyurethane foaming reactions. Experiments were performed with 10 wt% of lignin with various pHs in polyols. Virgin lignin (pH 2.5, 35% moisture) has the most negative impact as it reduces the initial foam rising rate by 85% and the foam's final height by 35% as compared to the reference foam, lignin free. Drying of this lignin at 80°C for 12 h can reduce this impact while alkaline treatment to bring the lignin's pH to 6.6 almost cancel it. As revealed by in situ dielectric constant measurements, both reactions, gelling via polymerization and blowing via CO₂ degassing, are impacted. In situ Fourier transform infrared analysis of the foaming process demonstrated that blowing reaction is the most pH sensitive. Two methods to counter the pH influence by pH modification were tested and provide interesting results but also significant drawbacks limiting their applicability.     

Cassette mutagenesis of Aspergillus awamori glucoamylase near its general acid residue to probe its catalytic and pH properties

Nine single amino add mutations in the active site of Aspergillusawamori glucoamylase were made by cassette mutagenesis to alterthe pH dependence of the enzyme and to determine possible functionsof the mutated residues. The Glul79-Asp mutation expressed inyeast led to a very large decrease in k_cat but to no changein K_m, verifying this residue's catalytic function. Aspl76-Gluand Glul80-Asp mutations affected K_m a more than k_cat, implyingthat Aspl76 and Glul80 are involved in substrate binding orstructural integrity. The Leul77-Asp mutation decreased k_catonly moderately, probably by changing the position of the generalacid catalytic group, and did not affect K_m. The Trpl78-Aspmutation greatly decreased k_cat while increasing K_m, showingthe importance of Trpl78 in the active site. Vall81-Asp andAsnl82-Asp mutations changed kinetk values little, suggestingthat Vall81 and Asnl82 are of minor catalytic and structuralimportance. Finally, insertions of Asp or Gly between residues176 and 177 resulted in almost complete loss of activity, probablycaused by destruction of the active site structure. No largechanges in pH dependence occurred in those mutations where kineticvalues could be determined, in spite of the increase in mostcases of the total negative charge. Increases in activationenergy of maltoheptaose hydrolysis in most of the mutant glucoamylasessuggested cleavage of individual hydrogen bonds in enzyme-substratecomplexes.