pH-responsive Poly Acrylic Acid Research Articles

PH-Responsive Cobalt(II)-Coordinated Assembly Containing Quercetin for Antimicrobial Applications.

The development of novel drug delivery systems (DDSs) with promising antibacterial properties is essential for facing the emergency of increasing resistance to antimicrobial agents. The antibacterial features of quercetin and its metal complexes have been broadly investigated. However, several drawbacks affect their activity and effectiveness. In this work, we propose a DDS based on a pH-responsive cobalt(II)-coordinated assembly containing quercetin and polyacrylic acid. This system is suggested to trigger the release of the model drug in a pH-dependent mode by exploiting the localized acidic environment at the bacterial infection sites under anaerobic conditions. The delivery system has been designed by accurately examining the species and the multiple equilibria occurring in solution among the assembly components. The formation of cobalt(II) complexes with quercetin in the absence or presence of the pH-responsive polyacrylic acid was investigated in buffered aqueous solution at pH 7.4 using spectrophotometric (UV-Vis) and calorimetric (ITC) techniques. The determined binding affinities and thermodynamic parameters that resulted are essential for the development of a DDS with improved binding and release capabilities. Furthermore, the affinity of the polymer-cobalt(II) complex toward the model antimicrobial flavonoid was explored at the solid-liquid interface by quartz crystal microbalance (QCM-D) experiments, which provided marked evidence for drug loading and release under pH control.

Polyurethane Shape Memory Polymer/pH-Responsive Hydrogel Hybrid for Bi-Function Synergistic Actuations

Stimuli-responsive actuating hydrogels response to the external stimulus with complex deformation behaviors based on the programmable anisotropic structure design are one of the most important smart soft materials, which have great potential applications in artificial muscles, smart values, and mini-robots. However, the anisotropic structure of one actuating hydrogel can only be programmed one time, which can only provide single actuating performance, and subsequently, has severely limited their further applications. Herein, we have explored a novel SMP/hydrogel hybrid actuator through combining polyurethane shape memory polymer (PU SMP) layer and pH-responsive polyacrylic-acid (PAA) hydrogel layer by a napkin with UV-adhesive. Owing to both the super-hydrophilicity and super-lipophilicity of the cellulose-fiber based napkin, the SMP and the hydrogel can be bonded firmly by the UV-adhesive in the napkin. More importantly, this bilayer hybrid 2D sheet can be programmed by designing a different temporary shape in heat water which can be fixed easily in cool water to achieve various fixed shapes. This hybrid with a fixed temporary shape can achieve complex actuating performance based on the bi-functional synergy of temperature-triggered SMP and pH-responsive hydrogel. The relatively high modulus PU SMP achieved high to 87.19% and 88.92% shape-fixing ratio, respectively, correspond to bending and folding shapes. The hybrid actuator can actuate with the 25.71 °/min actuating speed. Most importantly, one SMP/hydrogel bi-layer hybrid sheet was repeatedly programmed at least nine times in our research to fix various temporary 1D, 2D and 3D shapes, including bending, folding and spiraling shapes. As a result, only one SMP/hydrogel hybrid can provide various complex stimuli-responsive actuations, including the reversable bending-straightening, spiraling-unspiraling. A few of the intelligent devices have been designed to simulate the movement of the natural organisms, such as bio-mimetic "paw", "pangolin" and "octopus". This work has developed a new SMP/hydrogel hybrid with excellent multi-repeatable (≥9 times) programmability for high-level complex actuations, including the 1D to 2D bending and the 2D to 3D spiraling actuations, which also provides a new strategy to design other new soft intelligent materials and systems.

Tailoring Hydrogen-Bonding Strategy for Sequence-Dependent and Thermo/pH Dual-Responsive Clusteroluminescence.

Rational design of monomer sequence for desired properties is challenging. This study investigates the effect of monomer distribution of double hydrophilic copolymers (DHCs) with electron-rich units on cluster triggered emission (CTE) capacity. By means of combining latent monomer strategy, reversible addition fragmentation chain transfer (RAFT) polymerization and selective hydrolysis technology, the random, pseudo di-block and the gradient DHCs consisting of pH-responsive polyacrylic acid (PAA) segments and thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) segments were successfully synthesized in a controlled manner. Moreover, the gradient DHCs showed a tremendously increased luminescent intensity due to the distinct hydrogen-bonding interaction compared to random and pseudo di-block DHCs. To the best of our knowledge, this is the first reported the direct correlation between luminescent intensity and sequence structure of non-conjugated polymer. Meanwhile, thermo and pH dual-responsive clusteroluminescence could be easily performed. This work demonstrates a novel and facile method to tailor the hydrogen-bonding for the stimuli-responsive light-emitting polymers.

PH-responsive polyacrylic acid (PAA)-carboxymethyl cellulose (CMC) hydrogel incorporating halloysite nanotubes (HNT) for controlled curcumin delivery

A pH-sensitive nanocomposite based on halloysite nanotubes (HNT) coated with polyacrylic acid (PAA)/carboxymethyl cellulose (CMC) hydrogel was synthesized for controlled delivery of curcumin (CUR) to MCF-7 cancer cells. Hazelnut oil was added to minimize the nanocomposite size and increase its uniformity via water/oil/water (W/O/W) double emulsion method. Likewise, Span 80 surfactant was incorporated to produce a nanoniosomal emulsion that increased the stability and retention of CUR as an anticancer drug. The molecular interactions between the nanocomposite components, its crystalline structure, surface morphology, size distribution and surface charge were analyzed through Fourier transformed infrared (FT-IR) spectroscopy, field emission-scanning electron microscope (FE-SEM), X-ray diffraction (XRD), dynamic light scattering (DLS) and zeta potential measurements, respectively. The resulting drug delivery system showed a 45% drug loading and an 87% encapsulation efficiency, which are amongst the highest values reported up to date for CUR nanocarriers. The zeta potential of the nanocomposite was about 36 mV, indicating good stability. A sustained drug release was observed, with 61% and 96% CUR released at pH 7.4 and 5.4 after 96 h, respectively, which confirms the pH-sensitivity of the developed nanocarrier. MTT assay demonstrated the strong toxicity of the nanocomposites against MCF-7 cancer cells. Also, 46% of cell death rate in the apoptotic phase was observed by flow cytometry. The results obtained herein support the great potential of PAA/CMC/HNT/CUR hydrogel nanocomposites as smart drug delivery vehicles for breast cancer treatment.

Preparation and Permeation Properties of a pH-Responsive Polyacrylic Acid Coated Porous Alumina Membrane

A pH-responsive membrane is expected to be used for applications such as drug delivery, controlling chemical release, bioprocessing, and water treatment. Polyacrylic acid (PAA) is a pH-responsive polymer that swells at high pH. A tubular α-alumina porous support was coated with PAA by grafting to introduce appropriate functional groups, followed by polymerization with acrylic acid. The permeances of acetic acid, lactic acid, phenol, and caffeine were evaluated by circulating water inside the membrane, measuring the concentration of species that permeated into the water, and analyzing the results with the permeation model. The permeance of all species decreased with increasing pH, and that of phenol was the largest among these species. At high pH, the PAA carboxy group in the membrane dissociated into carboxy ions and protons, causing the swelling of PAA due to electrical repulsion between the negative charges of the PAA chain, which decreased the pore size of the membrane and suppressed permeation. Furthermore, the electrical repulsion between negatively charged species and the PAA membrane also suppressed the permeation. The results of this study demonstrated that the PAA-coated α-alumina porous support functioned as a pH-responsive membrane.

Multifunctional fish gelatin hydrogel inverse opal films for wound healing

BackgroundWound healing has become a worldwide healthcare issue. Attempts in the area focus on developing patches with the capabilities of avoiding wound infection, promoting tissue remolding, and reporting treatment status that are of great value for wound treatment.ResultsIn this paper, we present a novel inverse opal film (IOF) patch based on a photo-crosslinking fish gelatin hydrogel with the desired features for wound healing and dynamic monitoring. The film with vibrant structure colors was constructed by using the mixture of fish gelatin methacryloyl, chitosan, and polyacrylic acid (PAA) to replicate colloidal crystal templates. As the structures of these natural biomolecules are well-retained during the fabrication, the resultant IOF was with brilliant biocompatibility, low immunogenicity, antibacterial property, as well as with the functions of promoting tissue growth and wound healing. In addition, the IOF presented interconnected nanopores and high specific surface areas for vascular endothelial growth factor loading, which could further improve its angiogenesis capability. More attractively, as the pH-responsive PAA was incorporated, the IOF patch could report the wound healing status through its real-time structural colors or reflectance spectra.ConclusionsThese features implied the practical value of the multifunctional fish gelatin hydrogel IOFs in clinical wound management.Graphical

Anti‐cancer combination therapy by co‐delivery of hydrophilic and hydrophobic using dual temperature and pH‐responsive liposomes

A novel combination chemotherapic strategy by co-delivery of doxorubicin (DOX) and mitomycin C (MC) anti-cancers was reported using dual pH and temperature-responsive copolymer-modified liposomes to achieve superior therapeutic efficacy. The copolymer was prepared using temperature-responsive N-isopropylacrylamide and pH-responsive poly-acrylic acid monomers through reversible addition–fragmentation chain transfer polymerisation and revealed dual pH/temperature-dependent phase transitions proved by differential scanning colorimetric and cloud point measurements. With relatively high encapsulation efficiency of 81.2% for DOX and 77.3% for MC, the prepared polymer-modified responsive liposomes (PMRLs) have shown enhanced and controlled temperature/pH-dependent release profiles and significantly lower thermal dose thresholds with up to a 250-fold decrease at pH 7.4 and 1000-fold decrease at pH 5.5 compared to the traditional formulations. The temperature/pH-dependent release profile of the drugs was investigated in vitro and cytotoxicity of the carriers was evaluated using both normal and cancerous cell lines. It was found that the two drugs co-loaded PMRLs were revealed synergistic effects on cytotoxicity of the carriers against Michigan Cancer Foundation-7 breast cancer cells. The results revealed that by this combinational regimen, the prepared liposomes have the potential to dramatically decrease the risk of damage to healthy tissues normally caused by liposomal cancer therapy.

Self‐Regulating Cross‐Linked Graphene Oxide Membranes with Stable Retention Properties over a Wide pH Range

AbstractTo extend the effective working range of porous membranes is highly desirable for membrane applications. Here, graphene oxide (GO) based membranes capable of retaining stable retention properties with varying pH are reported. The self‐adjustable properties of GO based membranes are realized by coupling with pH‐responsive polyacrylic acid (PAA) molecules via a facile vacuum filtration process. With decreasing pH, the shrinkage of the molecular chains of PAA decreases the interlayer spacing of PAA/GO membranes, which compensates for the weakened Donnan effect in acidic conditions, leading to the stable retention properties of the membranes over a wide pH range. With PAA introduced, the laminated structure of the membranes is well preserved while the membrane thickness is slightly increased. PAA endows the membranes with obvious self‐alteration of pore structure in response to the change of pH. Nanofiltration performance measurements show that the dye retention properties of GO membranes decrease sharply when the pH changes from 9 to 1. However, the rejection rates of PAA/GO membranes could be well retained or even increased in acidic conditions. This work demonstrates that PAA is an effective pH‐sensitive modification material for fabricating GO‐based membranes with stable retention properties under varying pH.

Antifreezing and Stretchable Organohydrogels as Soft Actuators.

Inspired by the freezing tolerance performances found in living creatures, an effect approach is presented to develop novel antifreezing polymeric organohydrogel actuators. Through construction of a bilayer hydrogel including a nonresponsive polyacrylamide (PAAm) layer and a pH-responsive polyacrylic acid (PAA) layer in the presence of a mixed solvent of water and glycerol, organohydrogel actuators that could produce various shape deformations at subzero temperatures have been achieved, and the actuating speed could be tuned by adjusting the temperature and the ratio between glycerol and water. Moreover, a series of application demonstrations including a weightlifting robot, artificial valve, and robotic arm have been displayed. In addition, by introducing the ionic compound KI into the glycerol-based organogel, flexible conductors that could perform stable sensing performance over a wide range of temperatures from -30°C to 60°C have been developed.

Tailor-made pH-sensitive polyacrylic acid functionalized mesoporous silica nanoparticles for efficient and controlled delivery of anti-cancer drug Etoposide

A multifaceted therapeutic platform has been proposed for controlled delivery of Etoposide (ETS) leading to a synergistic advantage of maximum therapeutic efficacy and diminished toxicity. A state of the art pH responsive nanoparticles (NPs) MSNs-PAA consisting of mesoporous silica nanoparticles core and polymeric shell layers, were developed for controlled release of model anti-cancer drug ETS. Graft onto strategy was employed and amination served as an interim step, laying a vital foundation for functionalization of the MSN core with hydrophilic and pH responsive polyacrylic acid (PAA). MCM-41-PAA were investigated as carriers for loading and regulated release of ETS at different pH for the first time. The PAA-MSNs contained 20.19% grafted PAA as exhibited by thermogravimetric analysis (TGA), which enormously improved the solubility of ETS in aqueous media. The synthesized PAA-MSNs were characterized by various techniques viz, SEM-EDS, TEM, BET, FT-IR and powder XRD. ETS was effectively loaded into the channels of PAA-MSN via electrostatic interactions. The cumulative release was much rapid at extracellular tumor (6.8) and endosomal pH (5.5) than that of blood pH (7.4). Hemolysis study was done for the prepared NPs. MTT assay results showed that the drug-loaded ETS-MCM-41-PAA NPs were more cytotoxic to both prostate cancer cells namely PC-3 and LNCaP than free ETS, which was attributed to their slow and sustained release behavior. The above results confirmed that PAA-MSN hold a great potential as pH responsive carriers with promising future in the field of cancer therapy.

Preparation of polyacrylic acid (paa) films on porous silicon for drug storage/release applications.

Recent developments in controlled drug delivery technology has benefitted modern medicine by providing patients with efficient, noninvasive methods that enhance the action of drugs, reduce dosing frequency, and decrease adverse side-effects. Porous silicon (pSi) is an interesting platform from which drug delivery devices can be built because it is nontoxic, biodegradable, and can be prepared to have high surface area ratios for drug loading. In this work, porous silicon materials were prepared using an electrochemical etching method.Samples were characterized using infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Caffeine was selected as test drug for capture, storage, and release in pSi. To protect the drug from the external environment and enable its release a pH responsive polyacrylic acid (PAA) film was prepared on the pSi surface through a multistep process using (3- aminopropyl)triethoxysilane (APTES), α-bromoisobutyryl bromide (BIBB), and acrylic acid. FTIR spectra and AFM images acquired throughout the deposition process will be presented.

Development of a novel strategy for controlled release of lysozyme from whey protein isolate based active food packaging films

The purpose of this study is to develop a novel controlled release system based on pH-responsive polyacrylic acid (PAA)/lysozyme (LYS) complexes incorporated within a hydrophilic whey protein isolate (WPI) film matrix for active food packaging applications. Complex formation is simple under benign conditions that are suitable for preserving antimicrobial activity of the lysozyme. In addition, the pH-dependent charge density of complexes allowed a uniform distribution in the matrix. The properties of the complexes such as size, surface charge and hydrophilicity were varied by changing PAA/LYS ratio (0.1 and 0.3 w/w) and PAA molecular weight (2 kDa and 450 kDa). The effects of complex properties as well as mode of lysozyme incorporation into the films (100%-free, 50%-free+50%-PAA/LYS complex and 100%-PAA/LYS complex) on the LYS release rate, activity and antimicrobial efficacy of the films were investigated. The results have shown that ∼100% LYS loading into the complexes is possible regardless of PAA molecular weight or PAA/LYS ratio. Incorporating lysozyme into the film in complexed form extended its release time from less than 24 h up to 500 h and reduced its diffusivity from ∼10−9 to ∼10−13 cm2/s. The films including 50%-free-LYS+50%-PAA/LYS complex showed a 5.7 log reduction in bacterial population within 72 h whereas 100%-free-LYS containing film could not suppress Listeria innocua growth after 24 h. Overall, the results suggest that complexation of lysozyme with weak polyelectrolytes can be used as an effective strategy to achieve a long-lasting antimicrobial effect and that films prepared with such complexes have great potential as food packaging materials.

Synthesis of pH-responsive β-CD-based star polymer and impact of its self-assembly behavior on pectinase activity.

A novel type of pH-responsive star polymer based on β-cyclodextrin (β-CD) was synthesized and further covalently conjugated with enzyme. The impact of its self-assembly behavior on enzyme activity was investigated. In our design, azide containing the polymer (N3 )7 -β-CD-(PtBA)14 was synthesized via atom transfer radical polymerization of tert-butyl acrylate using (N3 )7 -β-CD-(Br)14 as the multifunctional initiator. The final product (N3 )7 -β-CD-(PAA)14 was obtained via hydrolysis and covalently conjugating pectinase onto pH-responsive polyacrylic acid (PAA) arms. PAA can change its conformation with the self-assembly by altered pH, leading its nanostructure into micellar nanoparticles in aqueous solution and further affecting the activity of immobilized pectinase. The results were proved by fluorescence spectroscopy and dynamic light scattering. This system proves that the activity of immobilized enzyme can be tailored predictably, and this pH-responsive polymer holds great potential for controllable delivery of enzymes.

Biodegradable pH-responsive polyacrylic acid derivative hydrogels with tunable swelling behavior for oral delivery of insulin

Novel biodegradable and pH-sensitive hydrogels composed of four types of pH-sensitive polyacrylic acid derivatives (PAAD) and a biodegradable poly(l-glutamic acid) (PGA) crosslinker were synthesized and characterized for oral delivery of proteins or peptides. The swelling ratios of hydrogels in buffer solutions showed a pH-dependent profile at different pH values. Insulin was loaded into the hydrogels as a model protein. The in vitro drug release experiment was carried out at different pH values and the release data suggested that both the pH and the type of the AAD unit played important roles in the drug release behaviors of the hydrogels. In vitro MTT assay indicated that the hydrogels displayed good cytocompatibility. After oral administration of insulin-loaded hydrogel particles to streptozotocin-induced diabetic rats at 60 IU/kg, the fasting plasma glucose level was reduced continuously to 67.4% within 7 h. These results indicated that the hydrogels are potential new vehicles for oral delivery of drugs.