Hydrogels, composed of hydrophilic homopolymer or copolymer networks, have structures similar to natural living tissues, making them ideal for applications in drug delivery, tissue engineering, and biosensors. Since Wichterle and Lim first synthesized hydrogels in 1960, extensive research has led to various types with unique features. Responsive hydrogels, which undergo reversible structural changes when exposed to stimuli like temperature, pH, or specific molecules, are particularly promising. Temperature-sensitive hydrogels, which mimic biological processes, are the most studied, with poly(N-isopropylacrylamide) (PNIPAm) being prominent due to its lower critical solution temperature of around 32 °C. Additionally, pH-responsive hydrogels, composed of polyelectrolytes, change their structure in response to pH variations. Despite their potential, conventional hydrogels often lack mechanical strength. The double-network (DN) hydrogel approach, introduced by Gong in 2003, significantly enhanced mechanical properties, leading to innovations like shape-deformable DN hydrogels, organic/inorganic composites, and flexible display devices. These advancements highlight the potential of hydrogels in diverse fields requiring precise and adaptable material performance. In this review, we focus on advancements in the field of responsive acrylamide-based hydrogels with IPN structures, emphasizing the recent research on DN hydrogels.

Six derivatives of poly-N-vinylcaprolactam (PNVCL) P1-P6 were synthesized via surfactant-free precipitation polymerization (SFPP) at 70 °C, with potassium persulfate (KPS) as the initiator. P5 and P6 were synthesized using the cross-linker N,N\'-Methylenebisacrylamide (MBA). The conductivity was measured to monitor the polymerization process. The hydrodynamic diameters (HDs) and polydispersity indexes (PDIs) of aqueous dispersions of P1-P6 were determined using dynamic light scattering (DLS) and zeta potential (ZP) using electrophoretic mobilities. At 18 °C for P1-P6, the HDs (nm) were 428.32 ± 81.30 and PDI 0.31 ± 0.19, 528.60 ± 84.70 (PDI 0.42 ± 0,04), 425.96 ± 115.42 (PDI 0.56 ± 0.08), 440.34 ± 106.40 (PDI 0.52 ± 0.09), 198.39 ± 225.35 (PDI 0.40 ± 0.19), and 1201.52 ± 1318.05 (PDI 0.71 ± 0.30), the and ZPs were (mV) 0.90 ± 3.23, -4.46 ± 1.22, -6.44 ± 1.82, 0.22 ± 0.48, 0.18 ± 0.79, and -0.02 ± 0.39 for P1-P6, respectively. The lower critical solution temperature ranged from 27 to 29 °C. The polymers were characterized using the ATR-FTIR method. The study concluded that the physicochemical properties of the product were significantly affected by the initial reaction parameters. Polymers P1-P4 and P6 have potential for use as drug carriers for skin applications.

Gold nanoparticles (AuNPs) possess attractive electronic, optical, and catalytic properties, enabling many potential applications. Poly(N-isopropyl acrylamide) (PNIPAAm) is a temperature-responsive polymer that changes its hydrophilicity upon a slight temperature change, and combining PNIPAAm with AuNPs allows us to modulate the properties of AuNPs by temperature. In a previous study, we proposed a simpler method for designing PNIPAAm-AuNP hybrid microgels, which used an AuNP monomer with polymerizable groups. The size of AuNPs is the most important factor influencing their catalytic performance, and numerous studies have emphasized the importance of controlling the size of AuNPs by adjusting their stabilizer concentration. This paper focuses on the effect of AuNP size on the catalytic activity of PNIPAAm-AuNP hybrid microgels prepared via the copolymerization of N-isopropyl acrylamide and AuNP monomers with different AuNP sizes. To quantitatively evaluate the catalytic activity of the hybrid microgels, we monitored the reduction of 4-nitrophenol to 4-aminophenol using the hybrid microgels with various AuNP sizes. While the hybrid microgels with an AuNP size of 13.0 nm exhibited the highest reaction rate and the apparent reaction rate constant (kapp) of 24.2 × 10-3 s-1, those of 35.9 nm exhibited a small kapp of 1.3 × 10-3 s-1. Thus, the catalytic activity of the PNIPAAm-AuNP hybrid microgel was strongly influenced by the AuNP size. The hybrid microgels with various AuNP sizes enabled the reversibly temperature-responsive on-off regulation of the reduction reaction.

Structurally well-defined small molecules with lower critical solution temperature (LCST) behavior offer enormous prospects for fine-tuning their phase transition properties to be \"on-demand\" applied in the specific scene but are still underexplored. Herein, a novel amphiphilic small LCST molecule is rationally designed and synthesized. The molecule, namely TG, features a conjugation of multiple short ethylene glycol (EG) chains with the functional coordinating terpyridine (Tpy) moiety. The molecule TG demonstrates excellent LCST behavior down to 0.05 × 10-3 m in a water solution. And a cloud point Tcp = 30.9 °C with a very short thermal hysteresis ΔT = 0.2 °C and good reversibility can be achieved when c = 0.1 × 10-3 m. The excellent LCST properties of TG have enabled its successful performance as the smart window for solar radiation management with the ∆Tlum, ∆TIR, and ∆Tsol being 83.6%, 49.1%, and 67.2%, respectively. Moreover, the presence of Tpy moiety in TG enables its coordination with Ru3+ and the resulting complex also exhibits modulated LCST behavior with different concentration-dependent Tcp. These studies would provide novel small-molecule-based scaffolds for constructing better solar radiation management systems as well as other thermal-responsive smart materials.

The effect of amphiphilic block copolymer polyethylene glycol (PEG)-polypropylene glycol (PPG)-PEG concentration in the polyphenylsulfone (PPSU) casting solution and coagulation bath temperature (CBT) on the structure, separation, and antifouling performance of PPSU ultrafiltration membranes was studied for the first time. According to the phase diagram obtained, PPSU/PEG-PPG-PEG/N-methyl-2-pyrrolidone (NMP) systems are characterized by a narrow miscibility gap. It was found that 20 wt.% PPSU solutions in NMP with the addition of 5-15 wt.% of PEG-PPG-PEG block copolymer feature upper critical solution temperature, gel point, and lower critical solution temperature. Membrane composition and structure were studied by Fourier-transform infrared spectroscopy, scanning electron and atomic force microscopies, and water contact angle measurements. The addition of PEG-PPG-PPG to the PPSU casting solution was found to increase the hydrophilicity of the membrane surface (water contact angle decreased from 78° for the reference PPSU membrane down to 50° for 20 wt.%PPSU/15 wt.% PEG-PPG-PEG membrane). It was revealed that the pure water flux increased with the rise of CBT from 18-20 L·m-2·h-1 for the reference PPSU membrane up to 38-140 L·m-2·h-1 for 20 wt.% PPSU/10-15 wt.% PEG-PPG-PEG membranes. However, the opposite trend was observed for 20 wt.% PPSU/5-7 wt.% PEG-PPG-PEG membranes: pure water flux decreased with an increase in CBT. This is due to the differences in the mechanism of phase separation (non-solvent-induced phase separation (NIPS) or a combination of NIPS and temperature-induced phase separation (TIPS)). It was shown that 20 wt.% PPSU/10 wt.% PEG-PPG-PEG membranes were characterized by significantly higher antifouling performance (FRR-81-89%, DRr-26-32%, DRir-10-20%, DT-33-45%) during the ultrafiltration of bovine serum albumin solutions compared to the reference PPSU membrane prepared at different CBTs (FRR-29-38%, DRr-6-14%, DRir-74-89%, DT-88-94%).

In this paper, the kinetic stability of Pickering emulsions stabilized by spherical silica particles (100 nm in diameter) was examined in the water - 2,6-lutidine mixture. In the close vicinity of the lower critical solution temperature, Pickering emulsions were unstable due to the ultra-low liquid-liquid interfacial tension but increased their stability with increasing the temperature. In this system, the interfacial tension obeys universal scale law and can be tuned by temperature without adding any surface-active agents. Owing to this unique feature, we elucidated the relation between the interfacial tension and the stability of Pickering emulsions.

Drug-releasing contact lenses are emerging therapeutic systems for treating ocular diseases. However, their applicability is limited by the burst release of drugs during lens wear and premature drug leakage during packaging, rendering the precise control of release duration or dose difficult. Here, we introduce a pH-sensitive contact lens exhibiting on-demand drug release only during lens wear and negligible premature drug leakage during packaging and transportation, which is accomplished by incorporating drug-loaded mesoporous silica nanoparticles (MSNs) coated with a pH-sensitive polymer into the contact lens. The compositionally optimized pH-sensitive polymer has a lower critical solution temperature (LCST) at >45 °C at pH 7.4, whereas its LCST decreases to <35 °C under acidic conditions (pH ∼ 6.5). Consequently, the MSN-incorporated contact lens sustainably releases the loaded drugs only in the acidic state at 35 °C, which corresponds to lens-wear conditions, through the MSN pores that open because of the shrinkage of polymer chains. Conversely, negligible drug leakage is observed from the contact lens under low-temperature or neutral-pH conditions corresponding to packaging and transportation. Furthermore, compared with the plain contact lens, the pH-sensitive contact lens exhibits good biocompatibility and unchanged bulk characteristics, such as optical (transmittance in the visible-light region), mechanical (elastic modulus and tensile strength), and physical (surface roughness, oxygen permeability, and water content) properties. These findings suggest that the pH-sensitive contact lens can be potentially applied in ocular disease treatment.

Degenerative intervertebral disc disease is a common source of chronic pain and reduced quality of life in people over the age of 40. While degeneration occurs throughout the disc, it most often initiates in the nucleus pulposus (NP). Minimally invasive delivery of NP cells within hydrogels that can restore and maintain the disc height while regenerating the damaged NP tissue is a promising treatment strategy for this condition. Towards this goal, a biohybrid ABA dimethacrylate triblock copolymer was synthesized, possessing a lower critical solution temperature below 37 °C and which contained as its central block an MMP-degradable peptide flanked by poly(trimethylene carbonate) blocks bearing pendant oligoethylene glycol groups. This triblock prepolymer was used to form macroporous NP cell-laden hydrogels via redox initiated (ammonium persulfate/sodium bisulfite) crosslinking, with or without the inclusion of thiolated chondroitin sulfate. The resulting macroporous hydrogels had water and mechanical properties similar to those of human NP tissue and were mechanically resilient. The hydrogels supported NP cell attachment and growth over 28 days in hypoxic culture. In hydrogels prepared with the triblock copolymer but without the chondroitin sulfate the NP cells were distributed homogeneously throughout in clusters and deposited collagen type II and sulfated glycosaminoglycans but not collagen type I. This hydrogel formulation warrants further investigation as a cell delivery vehicle to regenerate degenerated NP tissue. STATEMENT OF SIGNIFICANCE: The intervertebral disc between the vertebral bones of the spine consists of three regions: a gel-like central nucleus pulposus (NP) within the annulus fibrosis, and bony endplates. Degeneration of the intervertebral disc is a source of chronic pain in the elderly and most commonly initiates in the NP. Replacement of degenerated NP tissue with a NP cell-laden hydrogel is a promising treatment strategy. Herein we demonstrate that a crosslinkable polymer with a lower critical solution temperature below 37 °C can be used to form macroporous hydrogels for this purpose. The hydrogels are capable of supporting NP cells, which deposit collagen II and sulfated glycosaminoglycans, while also possessing mechanical properties matching those of human NP tissue.

Schizophrenic copolymers are one type of the popular smart polymers that show invertible colloidal structures in response to temperature stimulus. However, the lack of principles to predict the phase transition temperature of a schizophrenic copolymer from its corresponding parent thermo-responsive polymers limits their development. Additionally, studies on their applications remain scarce. Herein, a series of schizophrenic copolymers were synthesized by polymerization of a RAFT-made polymer precursor poly(acrylamide-co-N-acryloxysuccinimide-co-acrylic acid) (P(AAm-co-NAS-co-AAc)) with the mixture of N-isopropylmethacrylamide (NIPAm) and acrylamide (AAm) in varying molar ratios. In aqueous solution, the block P(AAm-co-NAS-co-AAc) and the block poly(NIPAm-co-AAm) exhibited upper and lower critical solution temperature (UCST and LCST) behavior, respectively. The schizophrenic copolymers featured either UCST-LCST, LCST-UCST, or only LCST thermo-responsive transition. A preliminary correlation of phase transition between the schizophrenic copolymers and their parent polymers was summarized. Furthermore, the co-assembly of the schizophrenic copolymers and proteins were conducted and the kinetics of protein loading and protein activity were investigated, which showed that the schizophrenic copolymers were efficient platforms for protein co-assembly with ultra-high protein loading while preserving the protein bioactivities. Additionally, all the materials were non-toxic towards NIH 3T3 and MCF-7 cells. This work offers the prospects of the schizophrenic polymers in soft colloidal and assembly systems, particularly in guiding the design of new materials and their use in biomedical applications.

Amorphous solid dispersions (ASDs) comprising an active pharmaceutical ingredient (API) and polymer are a frequently described approach in the formulation of new drug candidates. This study aimed to evaluate the saturation solubility and dissolution behavior of ASDs consisting of paracetamol (PCM) and polyvinylpyrrolidone/vinyl acetate (PVP/VA) in water and their influence on the transepithelial in vitro permeation of PCM. With increasing amounts of PVP/VA, the water solubility of ASDs containing PCM increased up to six times compared to that of a saturated PCM solution. In the case of preparations with 30 % PCM, two-phase separation was observed in water at room temperature, consisting of a polymer-rich phase with high API loading and an aqueous, polymer-poor phase. This result was attributed to the thermoresponsive behavior of PVP/VA with lower critical solution temperature (LCST). As the PCM content in the ASD increased, the LCST decreased. This behavior was analyzed by measuring the demixing temperature (Tdem) values with differential scanning calorimetry (DSC). Furthermore, the permeation behavior of PCM from these phase-separated preparations through Caco-2 cells was analyzed. Additionally, the effect of these preparations on cell viability was evaluated using the MTT assay. Preparations with relatively high PCM concentrations showed a reduction in cell viability.