Synthesis of pH-Responsive Multilayer Micelles for Sustained Release of Folic Acid

Two novel triblock copolymers poly(hydroxypropyl acrylate)-b-poly (methyl methacrylate)-b-poly(N,N-dimethylaminoethyl methacrylate) and poly(hydroxypropyl acrylate)-b-poly(methyl methacrylate)-b-poly(acrylic acid) were successfully synthesized. In acetone media, using the electrostatic interactions between N,N-dimethylaminoethyl methacrylate and acrylic acid units, they could form spherically shaped multilayer micelles with pH-responsive, and have a mean diameter around 110 nm. The critical micelle concentration of it was determined to be 2.42 mg/L. In vitro release experiments, the folic acid-loaded micelles exhibited sustained release behavior and the drug release rate was affected by the pH value of release media. These results indicate that the multilayer micelles may serve as a novel intelligent drug delivery system.     

Stimuli-Responsive Hydrogels Based on Random Copolymers of the Sucrose Methacrylate

Poly(sucrose methacrylate-co-acrylic acid), P(SMA-co-AA), and poly(sucrose methacrylate-co-diethylene glycol methyl ether methacrylate), P(SMA-co-EG₂MA), are synthesized by free radical polymerization using sucrose dimethacrylate as a crosslinker. The copolymers present one glass transition suggesting a random distribution of the comonomers. The copolymers–water interaction parameter χ is around 0.5, while M_c increases with SMA molar fraction. The kinetics of water swelling show a Fickian behavior for P(SMA-co-AA) richer in acrylic acid. The swelling is driven by the ionic character of the P(SMA-co-AA), except at pH = 2, and by the hydrophilicity of the SMA for the P(SMA-co-EG₂MA). The temperature influences the swelling behavior of the P(SMA-co-EG₂MA) due to the lower critical solution temperature (LCST) behavior. The pH- and thermoresponsiveness of the P(SMA-co-AA) and P(SMA-co-EG₂MA) hydrogels are maintained by replacing the sensitive comonomers with SMA up to mass fractions of 85 and 20 wt%, respectively, ≈71 and 17 wt% of sucrose, a product from a renewable resource. The hydrolytic degradation of the hydrogels is more pronounced for copolymers richer in SMA and resulted in sucrose release. Hydrogels present viscoelastic behavior, and the P(SMA-co-AA) series is more resistant to compression. The xerogels of the copolymers richer in SMA show a foam-like morphology with open cells.     

pH响应性乙烯-乙烯醇共聚物分离膜的纳滤特性

具有纳滤特性的pH响应性膜在小分子分离体系中具有广泛应用前景。文中以铸膜液浓度为25%的乙烯-乙烯醇共聚物(EVAL)超滤膜为基膜,接枝具有pH响应性的功能单体甲基丙烯酸二甲氨基乙酯,制备pH响应性EVAL膜,通过考察膜对标准物聚乙二醇(PEG)与无机盐的截留性能,研究其纳滤特性。结果表明,当pH小于pKa时,pH响应性EVAL膜对聚乙二醇(PEG)与无机盐的截留效果均明显高于未接枝膜,接枝率6%的接枝膜对PEG 800、PEG 1000及PEG 2000的截留率均达到90%以上,对二价阳离子的截留率达到80%以上,无机盐的截留顺序为:CaCl_2MgCl_2MgSO_4NaClNa2SO_4。当pH大于pKa时,PEG及无机盐截留率明显下降,膜对PEG 1000的截留率由95.6%降至62.9%,对MgCl_2截留率降至30.6%,截留率及膜水通量变化存在显著的pH响应性。     

On-Demand Removable Self-Healing and pH-Responsive Europium-Releasing Adhesive Dressing Enables Inflammatory Microenvironment Modulation and Angiogenesis for Diabetic Wound Healing

Current diabetic wound treatments remain unsatisfactory due to the lack of a comprehensive strategy that can integrate strong applicability (tissue adhesiveness, shape adaptability, fast self-healability, and facile dressing change) with the initiation and smooth connection of the cascade wound healing processes. Herein, benefiting from the multifaceted bonding ability of tannic acid to metal ions and various polymers, a family of tannin–europium coordination complex crosslinked citrate-based mussel-inspired bioadhesives (TE-CMBAs) are specially developed for diabetic wound healing. TE-CMBAs can gel instantly (< 60 s), possess favorable shape-adaptability, considerable mechanical strengths, high elasticity, considerable wet tissue adhesiveness (≈40 kPa), favorable photothermal antimicrobial activity, excellent anti-oxidant activity, biocompatibility, and angiogenetic property. The reversible hydrogen bond crosslinking and sensitive metal–phenolic coordination also confers TE-CMBAs with self-healability, pH-responsive europium ion and TA releasing properties and on-demand removability upon mixing with borax solution, enabling convenient painless dressing change and the smooth connection of inflammatory microenvironment modulation, angiogenesis promotion, and effective extracellular matrix production leveraging the acidic pH condition of diabetic wounds. This adhesive dressing provides a comprehensive regenerative strategy for diabetic wound management and can be extended to other complicated tissue healing scenarios.     

Synthesis of thermo- and pH-responsive polysilsesquioxane with carboxylic acid group

The thermoresponsive polysilsesquioxanes containing N-(methoxyethyl)methylamide structures with carboxylic acid groups were newly prepared. In the syntheses of the polysilsesquioxanes, the silane coupling reagent, obtained from the reaction of (3-isocyanatopropyl)trimethoxysilane and (2-methoxyethyl)methylamine, was used for the co-condensation with (3-mercaptopropyl)trimethoxysilane to give the polysilsesquioxane with mercapto group (MMEPSQ). MMEPSQ was employed as the intermediary compound to introduce carboxylic acid group through thiol-ene reaction. The polysilsesquioxane, which was prepared from the reaction of MMEPSQ and methacrylic acid showed the expected amphiphilic and thermoresponsive properties in an aqueous solution with addition of sodium hydroxide. The lower critical solution temperature (LCST) owing to hydrophobic aggregation increased with pH value of the aqueous solution. Furthermoe, the use of MMEPSQ for the reactions with maleic anhydride and successive ring-opening reaction by the amines, which contained pyridine or 15-crown-5-ether ring, enabled the formations of multi-functionalized polysilsesquioxanes. In the case of the polysilsesquioxane containing carboxylic acid groups and pyridine rings, the pyridinium salt structure was favorable to keep an enough solubility in water and the reversible thermoresponsive behavior. The polysilsesquioxane containing the crown ether and carboxylic acid groups, the selective ion recognition property to alkali metal ion was observed.     

欧车前胶-g-聚丙烯酸/黑云母高吸水性树脂的合成与溶胀行为

以欧车前胶（PSY）、丙烯酸（AA）和黑云母（BT）为原料,N,N′-亚甲基双丙烯酰胺（MBA）为交联剂,过硫酸铵（APS）为引发剂,采用水溶液聚合法制备了欧车前胶接枝聚丙烯酸复合黑云母（PSY-g-PAA/BT）高吸水性树脂。考察了不同含量BT树脂在蒸馏水和盐水中的吸水倍率和溶胀行为。红外光谱和溶胀性能测试结果表明,...     

pH响应性PAA/毒死蜱/氨基化介孔硅缓释体系的制备与性能

以共缩聚法合成氨基化介孔硅,采用浸渍法制备毒死蜱/氨基化介孔硅,并以带负电荷的聚丙烯酸（PAA）为功能分子,通过静电吸附作用制备了具有pH响应的PAA/毒死蜱/氨基化介孔硅缓释体系。利用XRD、N₂吸附-脱附、TEM、SEM、TG、Zeta电位和FTIR对PAA/毒死蜱/氨基化介孔硅的结构进行了表征,并探究了其在不同pH和温度下的释药行为。结果表明,PAA通过静电作用包覆于毒死蜱/氨基化介孔硅的表面。缓释体系的药物释放主要受到PAA的阻碍作用,PAA修饰载药氨基化介孔硅显示出明显的pH响应性,当pH≤7时,其药物释放速率随pH减小而增大,而在偏碱性条件下的释药速率稍大于中性环境。同时,载药体系的释药速率还受到温度的影响。其释药行为可用Korsmeryer-Pappas动力学模型来描述。     

pH-Responsive and Reversible A-Motif-Based DNA Hydrogel: Synthesis and Biosensing Application**

Functional DNA hydrogels with various motifs and functional groups require perfect sequence design to avoid cross-bonding interference with themselves or other structural sequences. This work reports an A-motif functional DNA hydrogel that does not require any sequence design. A-motif DNA is a noncanonical parallel DNA duplex structure containing homopolymeric deoxyadenosines (poly-dA) strands that undergo conformation changes from single strands at neutral pH to a parallel duplex DNA helix at acidic pH. Despite this and other advantages over other DNA motifs like no cross-bonding interference with other structural sequences, the A-motif has not been explored much. We successfully synthesized a DNA hydrogel by using an A-motif as a reversible handle to polymerize a DNA three-way junction. The A-motif hydrogel was initially characterized by electrophoretic mobility shift assay, and dynamic light scattering, which showed the formation of higher-order structures. Further, we used imaging techniques like atomic force microscopy and scanning electron microscope to validating its hydrogel like highly branched morphology. pH-induced conformation transformation from monomers to gel is quick and reversible, and was analysed for multiple acid-base cycles. The sol-to-gel transitions and gelation properties were further examined in rheological studies. The use of the A-motif hydrogel in the visual detection of pathogenic target nucleic acid sequence was demonstrated for the first time in a capillary assay. Moreover, pH-induced hydrogel formation was observed in situ as a layer over the mammalian cells. The proposed A-motif DNA scaffold has enormous potential in designing stimuli-responsive nanostructures that can be used for many biological applications.     

pH-responsive dual-functional hydrogel integrating localized delivery and anti-cancer activities for highly effective therapy in PDX of OSCC

As one of the most promising localized drug delivery systems for enhancing therapeutic efficacy and reducing systemic toxicity, supramolecular hydrogels self-assembled from natural products have recently attracted tremendous attention. However, the intricate drug loading process, limited drug entrapment efficacy, and lack of stimulus responsiveness considerably impede their potential for biological applications and raise the need for advanced hydrogel-based delivery systems. Therefore, the development of updated materials that integrate localized delivery and drug activity into a single system is extremely desired and has great potential to overcome the aforementioned shortcomings. In this study, a pH-responsive dual-functional isoG-based supramolecular hydrogel with both localized delivery and anti-cancer activity in one molecule is successfully developed in one pot by following a simple and green procedure. The isoguanosine-phenylboronic-guanosine (isoGPBG) hydrogel exhibits exceptional stability (more than one year), outstanding pH-responsiveness and excellent sustained release capability. Both in vitro and in vivo experiments demonstrate that the isoGPBG hydrogel not only shows acceptable biocompatibility and biodegradability but also significantly inhibit tumor growth (approximately 60% inhibition of tumor growth) and improve overall survival, especially in preclinical patient-derived xenograft (PDX) model of oral squamous cell carcinoma (OSCC). Therefore, the isoGPBG hydrogel, to the best of our knowledge, is the first example of pH-responsive dual-functional isoG-based supramolecular hydrogel integrating localized delivery and anti-cancer activity in one molecule. It is implied that the isoGPBG hydrogel could act as a smart dual-functional localized delivery system in the future for clinical cancer therapy.     

Hybrid Hydrogel-Magnet Actuators with pH-Responsive Hydrogels for Gastrointestinal Microrobots

Limited space on millimeter-scale devices for biomedical applications makes it challenging to incorporate bulky actuators and power for onboard mechanical actuation. Stimuli-responsive hydrogels, such as pH-responsive hydrogels, provide a solution to automatically sense and actuate in the gastrointestinal tract. However, hydrogels are often nonload bearing and slow in actuation. To overcome these challenges, a new type of hybrid actuator is developed which utilizes a pH-responsive hydrogel with magnets to trigger magnetic springs (i.e., permanent magnets with repulsive, spring-like forces) to quickly initiate rotational and translational movements at pH > 6. The agar-poly(acrylic acid) hydrogel undergoes a large volume transition at pH > 6 and exhibits large nominal blocking stress of 610–819 kPa for a 3–4 mm diameter cylinder hydrogel. Moreover, the scaling of hydrogel force and response times are experimentally confirmed. Based on the hydrogel properties, an analytical hydrogel model is developed to predict hydrogel force and displacement under varying magnetic loads and wall constraints in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 6.8), and the experimental data validate the model. Finally, an innovative hybrid hydrogel-magnet actuator that triggers rotational and translational motion without external activation is demonstrated.