pH-Responsive Charge-Conversion Progelator Peptides

A simple strategy for generating stimuli-responsive peptide-based hydrogels via charge-conversion of a self-assembling peptide (SAP) is described. These materials are formulated as soluble, polyanionic peptides, containing maleic acid, citraconic acid, or dimethylmaleic acid amide masking groups on each lysine residue, which do not form assemblies, but instead flow easily through high gauge needles and catheters. Acid-induced mask hydrolysis renews the zwitterionic nature of the peptides with concomitant and rapid self-assembly via β-sheet formation into rehealable hydrogels. The use of different masks enables one to tune pH responsiveness and assembly kinetics. In anticipation of their potential for in vivo hydrogel delivery and use, progelators exhibit hemocompatibility in whole human blood, and their peptide components are shown to be noncytotoxic. Finally, demonstration of stimuli-induced self-assembly for dye sequestration suggests a simple, non-covalent strategy for small molecule encapsulation in a degradable scaffold. In summary, this simple, scalable masking strategy allows for preparation of responsive, dynamic self-assembling biomaterials. This work sets the stage for implementing biodegradable therapeutic hydrogels that assemble in response to physiological, disease-relevant states of acidosis.     

A pH and Redox Dual Responsive 4-Arm Poly(ethylene glycol)-block-poly(disulfide histamine) Copolymer for Non-Viral Gene Transfection in Vitro and in Vivo

A novel 4-arm poly(ethylene glycol)-b-poly(disulfide histamine) copolymer was synthesized by Michael addition reaction of poly(ethylene glycol) (PEG) vinyl sulfone and amine-capped poly(disulfide histamine) oligomer, being denoted as 4-arm PEG-SSPHIS. This copolymer was able to condense DNA into nanoscale polyplexes (<200 nm in average diameter) with almost neutral surface charge (+(5–10) mV). Besides, these polyplexes were colloidal stable within 4 h in HEPES buffer saline at pH 7.4 (physiological environment), but rapidly dissociated to liberate DNA in the presence of 10 mM glutathione (intracellular reducing environment). The polyplexes also revealed pH-responsive surface charges which markedly increased with reducing pH values from 7.4–6.3 (tumor microenvironment). In vitro transfection experiments showed that polyplexes of 4-arm PEG-SSPHIS were capable of exerting enhanced transfection efficacy in MCF-7 and HepG2 cancer cells under acidic conditions (pH 6.3–7.0). Moreover, intravenous administration of the polyplexes to nude mice bearing HepG2-tumor yielded high transgene expression largely in tumor rather other normal organs. Importantly, this copolymer and its polyplexes had low cytotoxicity against the cells in vitro and caused no death of the mice. The results of this study indicate that 4-arm PEG-SSPHIS has high potential as a dual responsive gene delivery vector for cancer gene therapy.     

Towards recycling purpose: Converting PET plastic waste back to terephthalic acid using pH-responsive phase transfer catalyst

Converting polyethylene terephthalate (PET) wastes to its monomer and valuable chemicals via eco-friendly chemical method is still a challenge task. Previously, phase transfer catalysts used for alkaline hydrolysis were soluble in reaction media and hardly separated after reaction. Here, we reported several pH-responsive catalysts combined alkyl quaternary ammonium units with heteropolyacid anion for achieving stepwise product/catalyst separation and catalyst recycling. The properties of homogeneous/heterogeneous transfer behavior allow catalyst to be easily separated from reaction media by adjusting of pH value. Among them, [C₁₆H₃₃N(CH₃)₃]₃PW₁₂O₄₀ (abbreviated as [CTA]₃PW) exhibits the highest activity and the most suitable pH responsive values. Such a pH triggered switchable catalytic system not only shows good performance for depolymerization of pure PET, but also some real PET wastes such as coloured trays and PE/PET complex films could be completely degraded into terephthalic acid. Additionally, the reaction kinetics and activation energy of PET alkaline hydrolysis also studied with and without pH-responsive [CTA]₃PW.     

Reversible pH-Responsive Hydrogels of Softwood Kraft Lignin and Poly[(2-dimethylamino)ethyl Methacrylate]-based Polymers

Softwood kraft lignin (SKL) pH-responsive hydrogels were prepared through controlled aggregation using poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) and poly(2-(dimethylamino)ethyl methacrylate)-block-poly(ethylene oxide)-block-poly(2-(dimethylamino) ethyl methacrylate) triblock copolymer (PDMAEMA-co-PEO-co-PDMAEMA). At low SKL concentrations, the SKL/polymer (PDMAEMA and PDMAEMA-co-PEO-co-PDMAEMA) aqueous solutions exhibited pH-dependent aggregation arising from the formation of strong intermolecular hydrogen bonds. Decreasing the SKL/polymer weight ratio resulted in the pH-reversible soluble-insoluble (S-I) transition to become a soluble-insoluble-soluble (S-I-S) transition, which upon increasing the SKL concentration resulted in hydrogel formation. Under neutral conditions relatively strong hydrogels were formed, which upon either increasing or decreasing solution pH resulted in the hydrogels collapsing to liquid solutions, but were readily reformed upon neutralization. The effects of polymer structure, concentration, and intermolecular interactions on solution behavior and gelation are thoroughly discussed.     

Hollow MnO2/GNPs serving as a multiresponsive nanocarrier for controlled drug release

In this work, hollow manganese dioxide/gold nanoparticle (MnO₂/GNPs) hybrid drug nanocarriers were prepared by coupling the gold nanoparticles (GNPs) with hollow structure manganese dioxide (MnO₂). Among them, GNPs have been used as near-infrared (NIR)-responsive element for photothermal effect under NIR laser irradiation. The glutathione (GSH)-responsive and pH-responsive performances of drug release were derived from hollow MnO₂. Particularly, Doxorubicin hydrochloride (DOX) can be loaded into hollow MnO₂/GNPs with the drug loading efficiency up to 82.0%. Moreover, the photothermal effect and GSH-/pH-responsive properties of hollow MnO₂/GNPs were investigated. The hollow MnO₂/GNPs possessed satisfactory drug release efficiency (ca. 87.4% of loaded drug released in 12 h) and have high photothermal conversion efficiency, multiresponsive properties, and degradability. Finally, the kinetics of drug release was discussed in detail. Thus, our finding highlights that the multiresponsive nanocarriers are of great potential in the field of drug controlled release.     

pH-responsive drug delivery system based on hollow silicon dioxide micropillars coated with polyelectrolyte multilayers

We report on the fabrication of polyelectrolyte multilayer-coated hollow silicon dioxide micropillars as pH-responsive drug delivery systems. Silicon dioxide micropillars are based on macroporous silicon formed by electrochemical etching. Due to their hollow core capable of being loaded with chemically active agents, silicon dioxide micropillars provide additional function such as drug delivery system. The polyelectrolyte multilayer was assembled by the layer-by-layer technique based on the alternative deposition of cationic and anionic polyelectrolytes. The polyelectrolyte pair poly(allylamine hydrochloride) and sodium poly(styrene sulfonate) exhibited pH-responsive properties for the loading and release of a positively charged drug doxorubicin. The drug release rate was observed to be higher at pH 5.2 compared to that at pH 7.4. Furthermore, we assessed the effect of the number of polyelectrolyte bilayers on the drug release loading and release rate. Thus, this hybrid composite could be potentially applicable as a pH-controlled system for localized drug release.     

Encapsulation of magnetic nanoparticles in a pH-sensitive poly(4-vinyl pyridine) polymer: a step forward to a multi-responsive system

A multiresponsive system that consists on pH-responsive polymer microspheres with encapsulated iron oxide magnetic nanoparticles that rendered the core magnetic to enable externally controlled actuation under magnetic induction has been developed. The inorganic nanoparticles were first prepared and, then, further encapsulated in a pH-sensitive poly(4-vinylpyridine). These spheres have been obtained by a modification of the simple, rapid and high-reproducible nanoprecipitation method. Magnetic measurements showed that the iron oxide nanoparticles are superparamagnetic and, therefore, able to undergo a local increase of the temperature when an oscillating magnetic field is applied. Magnetically triggered heating and pH sensitivity can be useful for biomedical applications.     

Preparation and optimization of superabsorbent hydrogel micromatrices based on poly(acrylic acid), partly sodium salt-g-poly(ethylene oxide) for modified release of indomethacin

The purpose of this study was to prepare modified-release dosage of indomethacin (IND) in the form of micromatrices based on a superabsorbent hydrogel (SAH), poly(acrylic acid), partly sodium salt-g-poly(ethylene oxide) (PAAc-Na-g-PEO). A soaking procedure was used for the preparation of drug-loaded hydrogel micromatrices. The amount of IND, volume of drug-loading solution, and amount of PAAc-Na-g-PEO granules used for preparing micromatrices were the independent factors. The dependent factors were the measured responses from micromatrices, that is, percent recovery, percent entrapment efficiency, and the time at which 63.2% of the drug was released (T_d, minutes). A three-factor, three-level full factorial design (33) was created to optimize formulations. Nonlinear regression analysis indicated a good correlation between the measured responses and the independent factors. Optimum responses were obtained from medium levels of IND and SAH and low level of drug-loading solution. Differential scanning calorimetry, X-ray diffraction analysis, and scanning electron micrography indicated that IND crystals are physically adsorbed into the pores and irregular spaces of the hydrogel.     

PEGylation and aqueous solution behaviour of pH responsive poly(l-lysine iso-phthalamide)

The effect of PEGylation on the aqueous solution properties of a pH responsive pseudopeptide, poly(l-lysine iso-phthalamide), has been investigated using UV and fluorescence spectroscopy, ¹H NMR spectroscopy and dynamic light scattering. It was demonstrated that the level of PEGylation had a critical effect on the pH response of the parent polymer. When the degree of PEGylation was less than 23.4 wt% the modified polymer exhibited a transition from an expanded structure at high degrees of ionization to a compact hydrophobically stabilised structure at low degrees of ionization. The specific pH at which the conformational transition occurred was dependent on the degree of PEGylation. At levels of PEGylation in excess of 25.6 wt% the polymer no longer displayed this pH dependent conformation and existed in a micellar form (100-200 nm) over the whole range of ionization. Both linear and micellar forms of the pseudopeptide have applications in drug delivery.