Search Results (68)

Postoperative adhesions are a prevalent complication following abdominal surgeries, often leading to significant clinical challenges. This study introduces an innovative solution utilizing a polyethylene glycol (PEG)-based triblock copolymer to form an injectable, self-healing hydrogel aimed at preventing these adhesions. The hydrogel, formulated with temperature-responsive and self-healing properties through the incorporation of poly (N-isopropyl acrylamide) (PNIPAM) and anion–pi interactions, was synthesized using reversible addition–fragmentation chain transfer (RAFT) polymerization. The hydrogel’s physical properties, biocompatibility, hemostatic effect, and anti-adhesive capabilities were rigorously tested through in vitro and in vivo experiments involving rat models. It demonstrated excellent biocompatibility, effective tissue adhesion, and robust hemostatic properties. Most notably, it exhibited significant anti-adhesive effects in a rat abdominal wall–cecum model, reducing adhesion formation effectively compared to controls. The PEG-based injectable hydrogel presents a promising approach for postoperative adhesion prevention. Its ability to gel in situ triggered by body heat, coupled with its self-healing properties, provides a substantial advantage in clinical settings, indicating its potential utility as a novel anti-adhesion material. Full article

Stimuli-responsive polymers (SRPs) have garnered significant attention in recent decades due to their immense potential in biomedical and environmental applications. When these SRPs are grafted onto magnetic nanoparticles, they form multifunctional nanocomposites capable of various complex applications, such as targeted drug delivery, advanced separations, and magnetic resonance imaging. In this study, we employed a one-step hydrothermal method using 3-aminopropyltrimethoxysilane (APTES) to synthesize APTES-modified Fe₃O₄ nanoparticles (APTES@Fe₃O₄) featuring reactive terminal amine groups. Subsequently, via two consecutive surface-initiated atom transfer radical polymerizations (SI-ATRP), pH- and temperature-responsive polymer blocks were grown from the Fe₃O₄ surface, resulting in the formation of poly(itaconic acid)-block-poly(N-isopropyl acrylamide) (PIA-b-PNIPAM)-grafted nanomagnetic particles (PIA-b-PNIPAM@Fe₃O₄). To confirm the chemical composition and assess how the particle morphology and size distribution of these SRP-based nanocomposites change in response to ambient pH and temperature stimuli, various characterization techniques were employed, including transmission electron microscopy, differential light scattering, and Fourier transform infrared spectroscopy. The results indicated successful synthesis, with PIA-b-PNIPAM@Fe₃O₄ demonstrating sensitivity to both temperature and pH. Full article

In this project, a new class of temperature- and pH-sensitive hydrogel consisting of N-isopropyl acrylamide (NIPAM), hydroxyethyl methacrylate (HEMA), and acrylamide (AAm) was prepared via a controlled route through the reversible addition–fragmentation chain-transfer (RAFT) polymerization process. Poly(ethyleneglycol) dimethacrylate (PEG-DMA) was used as a long-chain hydrophilic and biocompatible crosslinking agent. The hydrogel structure was confirmed by different characteristic techniques such as ¹H NMR, FT-IR, and SEC, and the morphology and particle diameters were checked via the scanning electron microscopy (SEM) and dynamic light scattering (DLS) methods. Afterward, the as-prepared hydrogel, poly(NIPAM-co-HEMA-co-AAm), was loaded with doxorubicin (DOX) to be used as a temperature- and pH-triggered delivery carrier. The prepared system released DOX slowly at 37 °C and neutral pH, but increased DOX release significantly at 42 °C and acidic pH. The anti-cancer efficiencies of free DOX, hydrogel, and the DOX–hydrogel conjugate were tested in vitro using human colorectal adenocarcinoma HT-29 cell lines. Cytotoxicity evaluation of free DOX compared with the DOX–hydrogel conjugate revealed that more cancer cells were killed with increasing concentration. Moreover, the DOX-mediated apoptosis and ROS levels showed the beneficial effects of poly(NIPAM-co-HEMA-co-AAm) hydrogel for cancer drug delivery. Generally, the results suggest that this system can be a potential candidate for designing drug delivery systems. Full article

Tuning the critical solution temperature (CST) of thermoresponsive polymers is essential to exploit their immense potential in various applications. In the present study, the effect of PEG-methyl ether methacrylate with a higher molecular weight of 1100 g/mol (mPEGMA₁₁₀₀) as a comonomer was investigated for its suitability for the CST adjustment of LCST-type polymers. Accordingly, a library of mPEGMA₁₁₀₀-based copolymers was established with varying compositions (X_mPEGMA1100) using four main comonomers, namely di(ethylene glycol) ethyl ether acrylate, N-isopropyl acrylamide and methacrylamide, and mPEGMA₃₀₀, with different CST values (cloud points, T_CP, and clearing points, T_CL, by turbidimetry). It was found that less than 20 mol% of the mPEGMA₁₁₀₀ in the copolymers is practically sufficient for tuning the CST in the entire measurable temperature range, i.e., up to 100 °C, regardless of the CST of the homopolymer of the main comonomer (CST₀). Moreover, a predictive asymptotic model was developed based on the measured CST values, which strikingly revealed that the CSTs of mPEGMA₁₁₀₀-containing copolymers depend only on the two main parameters of these copolymers, X_mPEGMA1100 and the CST of the homopolymer of the main comonomer (CST₀), that is, CST = f(CST₀, X_mPEGMA1100). The revealed two-parameter relationship defines a surface in 3D plotting, and it is applicable to determine the CST of copolymers in advance for a given composition or to define the suitable composition for a required CST value. These unprecedented results on the dependence of CSTs on two major well-defined parameters enable to design a variety of novel macromolecular structures with tailored thermoresponsive properties. Full article

In this article, we report on the alginate heterografted by Poly(N-isopropyl acrylamide-co-N-tert-butyl acrylamide) and Poly(N-isopropyl acrylamide) (ALG-g-P(NIPAM86-co-NtBAM14)-g-PNIPAM) copolymer thermoresponsive hydrogel, reinforced by substituting part of the 5 wt% aqueous formulation by small amounts of Poly(acrylic acid)-g-P(boc-L-Lysine) (PAA-g-P(b-LL)) graft copolymer (up to 1 wt%). The resulting complex hydrogels were explored by oscillatory and steady-state shear rheology. The thermoresponsive profile of the formulations were affected remarkably by increasing the PAA-g-P(b-LL) component of the polymer blend. Especially, the sol-gel behavior altered to soft gel–strong gel behavior due to the formation of a semi-interpenetrating network based on the hydrophobic self-organization of the PAA-g-P(b-LL). In addition, the critical characteristics, namely T_{c,thermothickening} (temperature above which the viscosity increases steeply) and ΔT (transition temperature window), shifted and broadened to lower temperatures, respectively, due to the influence of the hydrophobic side chains P(b-LL) on the LCST of the PNIPAM-based grafted chains of the alginate. The effect of ionic strength was also examined, showing that this is another important factor affecting the thermoresponsiveness of the hydrogel. Again, the thermoresponsive profile of the hydrogel was changed significantly by the presence of salt. All the formulations showed self-healing capability and tolerance injectability, suitable for potential bioapplications in living bodies. Full article

The synthesis of poly(N-isopropyl acrylamide) (pNIPA)-based polymers via the surfactant-free precipitation polymerization (SFPP) method produced thermosensitive nanospheres with a range of distinctive physicochemical properties. Nano- and microparticles were generated using various initiators, significantly influencing particle characteristics, including the hydrodynamic diameter (D_H), which varied from 87.7 nm to 1618.1 nm. Initiators, such as potassium persulfate and 2,2′-azobis(2-methylpropionamidine) dihydrochloride, conferred anionic and cationic functionalities, respectively, impacting the electrokinetic potential (EP) of the particles. Notably, certain particles with cationic initiators exhibited negative EP values at 18 °C, attributed to residual initiator components that affected the surface charge distribution. The presence of hydrophilic N-(2-hydroxyethyl)acrylamide (HEAA) segments also influenced solubility and phase transition behaviors, with critical dependencies on the HEAA/NIPA (N-isopropyl acrylamide) molar ratios. EP measurements taken at 18 °C and 42 °C revealed substantial differences, primarily governed by the initiator type and polymer composition. Observed variations in particle stability and size were associated with the choice of crosslinking agents and comonomer content, which affected both D_H and EP in distinct ways. This study provides insights into key factors influencing colloidal stability and electrostatic interactions within thermosensitive polymer systems, underscoring their potential applications in biomedical and industrial fields. Full article

Surface-based biosensors have proven to be of particular interest in the monitoring of human pathogens by means of their distinct nucleic acid sequences. Genosensors rely on targeted gene/DNA probe hybridization at the surface of a physical transducer and have been exploited for their high specificity and physicochemical stability. Unfortunately, these sensing materials still face limitations impeding their use in current diagnostic techniques. Most of their shortcomings arise from their suboptimal surface properties, including low hybridization density, inadequate probe orientation, and biofouling. Herein, we describe and compare two functionalization methodologies to immobilize DNA probes on a glass substrate via a thermoresponsive polymer in order to produce genosensors with improved properties. The first methodology relies on the use of a silanization step, followed by PET-RAFT of NIPAM monomers on the coated surface, while the second relies on vinyl sulfone modifications of the substrate, to which the pre-synthetized PNIPAM was grafted to. The functionalized substrates were fully characterized by means of X-ray photoelectron spectroscopy for their surface atomic content, fluorescence assay for their DNA hybridization density, and water contact angle measurements for their thermoresponsive behavior. The antifouling properties were evaluated by fluorescence microscopy. Both immobilization methodologies hold the potential to be applied to the engineering of DNA biosensors with a variety of polymers and other metal oxide surfaces. Full article

The ability of thermoresponsive polymers to respond to temperature with a reversible conformational change makes them promising ‘smart’ materials for solutions in medical and biotechnological applications. In this work, two such polymers and structural isomers were studied: poly(N-isopropyl acrylamide) (PNiPAm) and poly(2-isopropyl-2-oxazoline) (PiPOx). We compare the critical solution temperatures (CST) of these polymers in D₂O and H₂O in the presence of Hofmeister series salts, as results obtained under these different solvent conditions are often compared. D₂O has a higher dipole moment and electronegativity than H₂O, which could significantly alter the CST transition. We used two complementary methods to measure the CST, dynamic light scattering (DLS) and differential scanning calorimetry (DSC) and found that the CST decreased significantly in D₂O compared to H₂O. In the presence of highly concentrated kosmotropes, the CST of both polymers decreased in both solvents. The influence of the kosmotropic anions was smaller than the water isotope effect at low ionic strengths but considerably higher at physiological ionic strengths. However, the Hofmeister anion effect was quantitatively different in H₂O than in D₂O, with the largest relative differences observed for Cl⁻, where the CSTs in D₂O decreased more than in H₂O measured by DLS but less by DSC. PiPOx was more sensitive than PNiPAm to the presence of chaotropes. It exhibited much higher transition enthalpies and multistep transitions, especially in aqueous solutions. Our results highlight that measurements of thermoresponsive polymer properties in D₂O cannot be compared directly or quantitatively to application conditions or even measurements performed in H₂O. Full article

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 (k_app) of 24.2 × 10⁻³ s⁻¹, those of 35.9 nm exhibited a small k_app 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. Full article

A hybrid synthetic-natural, thermoresponsive graft copolymer composed of poly(N-isopropyl acrylamide) (PNIPAM) side chains, prepared via RAFT polymerization, and a chitosan (Chit) polysaccharide backbone, was synthesized via radical addition-fragmentation reactions using the “grafting to” technique, in aqueous solution. ATR-FTIR, TGA, polyelectrolyte titrations and ¹H NMR spectroscopy were employed in order to validate the Chit-g-PNIPAM copolymer chemical structure. Additionally, ¹H NMR spectra and back conductometric titration were utilized to quantify the content of grafted PNIPAM side chains. The resulting graft copolymer contains dual functionality, namely both pH responsive free amino groups, with electrostatic complexation/coordination properties, and thermoresponsive PNIPAM side chains. Particle size measurements via dynamic light scattering (DLS) were used to study the thermoresponsive behavior of the Chit-g-PNIPAM copolymer. Thermal properties examined by TGA showed that, by the grafting modification with PNIPAM, the Chit structure became more thermally stable. The lower critical solution temperature (LCST) of the copolymer solution was determined by DLS measurements at 25–45 °C. Furthermore, dynamic and electrophoretic light scattering measurements demonstrated that the Chit-g-PNIPAM thermoresponsive copolymer is suitable of binding DNA molecules and forms nanosized polyplexes at different amino to phosphate groups ratios, with potential application as gene delivery systems. Full article

The aim of this study was to characterize and compare the zeta potential of particles sensitive to external thermal stimuli. Poly N-(isopropyl) acrylamide (PNIPA) was selected as the thermosensitive polymer with a volume phase transition temperature (VPTT) between 32 and 33 °C. The hydrodynamic diameter (D_H) of the nanoparticles was measured by dynamic light scattering. Zeta potential (ZP) measurements were performed with the same instrument used for D_H measurements. ZP measurements allow the prediction of the stability of colloidal systems in aqueous solutions. These measurements were combined with a pH study before and after the purification process of the particles. The ZP was measured to determine the electrostatic interactions between the particles, which can lead to particle aggregation and decrease their colloidal stability. The effect of the composition of the synthesized particles on the ZP was assessed. One of the most important factors influencing ZP is pH, especially in aqueous solutions. The initiator did not significantly affect the D_H of the particles, but it did significantly affect the ZP. The synthesized particles were subjected to a visible radiation absorption study in the selected temperature range to determine the VPTT. Full article

The regulated and targeted administration of hydrophobic and hydrophilic drugs is both promising and challenging in the field of drug delivery. Developing a hydrogel which is responsive to dual stimuli is considered a promising and exciting research area of study. In this work, melamine functionalized poly-N-isopropyl acrylamide-co-glycidyl methacrylate copolymer has been developed by copolymerizing glycidyl methacrylate (GMA) monomer with N-isopropyl acrylamide (NIPAm) and further functionalized with melamine units (pNIPAm-co-pGMA-Mela). The prepared pNIPAm-co-pGMA-Mela copolymer hydrogel was characterized using various characterization techniques, including ¹H NMR, FTIR, SEM, zeta potential, and particle size analysis. A hydrophobic drug (ibuprofen, Ibu) and hydrophilic drug (5-fluorouracil, 5-Fu) were selected as model drugs. Dual pH and temperature stimuli-responsive drug release behavior of the pNIPAm-co-pGMA-Mela hydrogel was evaluated under different pH (pH 7.4 and 4.0) and temperature (25 °C, 37 °C, and 45 °C) conditions. Furthermore, the in vitro biocompatibility of the developed pNIPAm-co-pGMA-Mela copolymer hydrogel was determined on MDA-MB-231 cells. The pH and temperature-responsive drug delivery study results reveal that the pNIPAm-co-pGMA-Mela hydrogel system is responsive to both pH and temperature stimuli and exhibits about ~100% of Ibu and 5-Fu, respectively, released at pH 4.0/45 °C. Moreover, the MTT assay and hemocompatibility analysis results proved that the pNIPAm-co-pGMA-Mela hydrogel system is biocompatible and hemocompatible, suggesting that that it could be used for drug delivery applications. The experimental results suggest that the proposed pNIPAm-co-pGMA-Mela hydrogel system is responsive to dual pH and temperature stimuli, and could be a promising drug carrier system for both hydrophilic and hydrophobic drug delivery applications. Full article

Despite advances in breast cancer treatment, there remains a need for local management of noninvasive, low-grade ductal carcinoma in situ (DCIS). These focal lesions are well suited for local intraductal treatment. Intraductal administration supported target site drug retention, improved efficacy, and reduced systemic exposure. Here, we used a poly(N-isopropyl acrylamide, pNIPAM) nanoparticle delivery system loaded with cytotoxic piplartine and an MAPKAP Kinase 2 inhibitor (YARA) for this purpose. For tumor environment targeting, a collagen-binding peptide SILY (RRANAALKAGELYKSILYGSG-hydrazide) was attached to pNIPAM nanoparticles, and the nanoparticle diameter, zeta potential, drug loading, and release were assessed. The system was evaluated for cytotoxicity in a 2D cell culture and 3D spheroids. In vivo efficacy was evaluated using a chemical carcinogenesis model in female Sprague–Dawley rats. Nanoparticle delivery significantly reduced the IC₅₀ of piplartine (4.9 times) compared to the drug in solution. The combination of piplartine and YARA in nanoparticles further reduced the piplartine IC₅₀ (~15 times). Treatment with these nanoparticles decreased the in vivo tumor incidence (5.2 times). Notably, the concentration of piplartine in mammary glands treated with nanoparticles (35.3 ± 22.4 μg/mL) was substantially higher than in plasma (0.7 ± 0.05 μg/mL), demonstrating targeted drug retention. These results indicate that our nanocarrier system effectively reduced tumor development with low systemic exposure. Full article

Temperature-responsive separation membranes can significantly change their permeability and separation properties in response to changes in their surrounding temperature, improving efficiency and reducing membrane costs. This study focuses on the modification of polyvinylidene fluoride (PVDF) membranes with amphiphilic temperature-responsive copolymer and inorganic nanoparticles. We prepared an amphiphilic temperature-responsive copolymer in which the hydrophilic poly(N-isopropyl acrylamide) (PNIPAAm) was side-linked to a hydrophobic polyvinylidene fluoride (PVDF) skeleton. Subsequently, PVDF-g-PNIPAAm polymer and graphene oxide (GO) were blended with PVDF to prepare temperature-responsive separation membranes. The results showed that temperature-responsive polymers with different NIPAAm grafting ratios were successfully prepared by adjusting the material ratio of NIPAAm to PVDF. PVDF-g-PNIPAAm was blended with PVDF with different grafting ratios to obtain separate membranes with different temperature responses. GO and PVDF-g-PNIPAAm formed a relatively stable hydrogen bond network, which improved the internal structure and antifouling performance of the membrane without affecting the temperature response, thus extending the service life of the membrane. Full article

Polymeric drug delivery technology, which allows for medicinal ingredients to enter a cell more easily, has advanced considerably in recent decades. Innovative medication delivery strategies use biodegradable and bio-reducible polymers, and progress in the field has been accelerated by future possible research applications. Natural polymers utilized in polymeric drug delivery systems include arginine, chitosan, dextrin, polysaccharides, poly(glycolic acid), poly(lactic acid), and hyaluronic acid. Additionally, poly(2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide), poly(ethylenimine), dendritic polymers, biodegradable polymers, and bioabsorbable polymers as well as biomimetic and bio-related polymeric systems and drug-free macromolecular therapies have been employed in polymeric drug delivery. Different synthetic and natural biomaterials are in the clinical phase to mitigate different diseases. Drug delivery methods using natural and synthetic polymers are becoming increasingly common in the pharmaceutical industry, with biocompatible and bio-related copolymers and dendrimers having helped cure cancer as drug delivery systems. This review discusses all the above components and how, by combining synthetic and biological approaches, micro- and nano-drug delivery systems can result in revolutionary polymeric drug and gene delivery devices. Full article