Search Results (62)

For decades, endovascular embolization (EE) has been a common technique for the treatment of several vascular abnormalities where the affected vessel is occluded using biocompatible embolic agents. In this work, we developed a NIPAAm-based temperature responsive, dual-crosslinking biocompatible and non-toxic injectable hydrogel system as a liquid embolic agent for EE. The swelling and mechanical properties of the hydrogel were tuned and optimized for its in vivo application. The in vivo study was carried out with nine swine models, including three animals for exploratory study and six animals for acute confirmatory study for the occlusion of surgically created aneurysm and rete mirabile. The polymer hydrogel was delivered into the vascular malformation sites using a catheter guided by angiography. After the injection, the liquid embolic agent was transformed into a solid implant in situ via cross-linking through chemical and thermal processes. During the exploratory study, it was observed that one of the three aneurysms and all the RMs were occluded. During the acute confirmatory study, all the aneurysms and the RMs of six animals were successfully occluded. Overall, our study presents the construction and characterization of a novel injectable hydrogel system capable of successfully occluding vascular malformation in large animals. In the future, after further modification and validation, this material may be used as a liquid embolic agent in clinical studies. Full article

A smart viscose fabric with temperature and pH responsiveness and proactive antibacterial and UV protection was developed. PNCS (poly-(N-isopropylakrylamide)/chitosan) hydrogel was used as the carrier of silver nanoparticles (Ag NPs), synthesised in an environmentally friendly manner using AgNO₃ and a sumac leaf extract. PNCS hydrogel and Ag NPs were applied to the viscose fabric by either in situ synthesis of Ag NPs on the surface of viscose fibres previously modified with PNCS hydrogel, or by the direct immobilisation of Ag NPs by the dehydration/hydration of the PNCS hydrogel with the nanodispersion of Ag NPs in the sumac leaf extract and subsequent application to the viscose fibres. Compared to the pre-functionalised PNCS application method, the in situ functionalisation imparted much higher concentration of Ag NPs on the fibres, colouring the samples brown to brown-green. These samples showed more than 90% reduction in the test bacteria E. coli and S. aureus and provided excellent UV protection. In this case, the PNCS hydrogel acted as a reservoir for Ag NPs, whose release was based on a diffusion-controlled mechanism. Despite the Ag NPs decreasing the responsiveness of the PNCS hydrogel, the moisture management was still preserved in the modified samples. Accordingly, the PNCS hydrogel is a suitable carrier for biosynthesized Ag NPs to tailor the protective smart surface of viscose fibres. Full article

An imbalance in the body’s pH or temperature may modify the immune response and result in ailments such as autoimmune disorders, infectious diseases, cancer, or diabetes. Dual pH- and thermo-responsive carriers are being evaluated as advanced drug delivery microdevices designed to release pharmaceuticals in response to external or internal stimuli. A novel drug delivery system formulated as hydrogel was developed by combining a pH-sensitive polymer (the “biosensor”) with a thermosensitive polymer (the delivery component). Thus, the hydrogel was created by cross-linking, using a solvent-free thermal approach, of poly(N-isopropylacrylamide-co-N-hydroyethyl acrylamide), P(NIPAAm-co-HEAAm), and poly(methylvinylether-alt-maleic acid), P(MVE/MA). The chemical structure of the polymers and hydrogels was analyzed using Fourier-transform infrared (FTIR) and proton nuclear magnetic resonance (¹H NMR) spectroscopies. The pH/thermosensitive hydrogel loses its thermosensitivity under physiological conditions but, remarkably, can recover the thermosensitive capabilities when certain physiologically active biomolecules, acting as triggering agents, electrostatically interact with pH-sensitive units. Our research aimed to develop a drug delivery system that could identify the disturbance of normal physiological parameters and instantaneously send a signal to thermosensitive units, which would collapse and modulate the release profiles of the drug. Full article

This study aims to design microgels that are thermo- and pH-sensitive for controlled doxorubicin (Dox) release in response to tumor microenvironment changes. N-isopropylacrylamide (NIPAAm) is widely used for thermoresponsive tumor-targeted drug delivery systems for the release of therapeutic payloads in response to temperature changes. Herein, a NIPAAm microgel (MP) that is responsive to temperature and pH was designed for the smart delivery of Dox. MP was made from NIPAAm, and polyethylene glycol methyl ether methacrylate (PEGMA) was copolymerized with 5%, 10%, or 15% mol of methacryloylamido hexanoic acid, (CAM5) an amphiphilic acid. We characterized the microgels using FTIR-ATR, DLS, and FESEM. The MP 10% CAM5 exhibited a particle size of 268 nm, with a transition temperature of 44 °C. MP had a drug loading capacity of 13% and entrapment efficiency of 87%. Nearly 100% of the Dox was released at pH 5 and 42 °C, compared to 30% at pH 7.4 and 37 °C. MP 10% CAM5 showed cytocompatibility in HeLa cells using the MTT assay. However, the cell viability assay showed that dox-MP was twice as effective as free Dox. Specifically, 3 μg/mL of free Dox resulted in 74% cell viability, while the same doses of Dox in NP reduced it to 35%. These results are promising for the future tumor-targeted delivery of antineoplastic-drugs, as they may reduce the side effects of Dox. Full article

A series of copolymers containing a thermo-responsive biocompatible first block of poly[di(ethylene glycol) methyl ether methacrylate)-co-(oligo(ethylene glycol) methyl ether methacrylate], P(DEGMA-co-OEGMA) were chain-extended to incorporate either poly(N-isopropylacrylamide), PNIPAAm or poly(N-isopropylacrylamide-co-butyl acrylate), P(NIPAAm-co-BA) as second thermo-responsive block using reversible addition–fragmentation chain transfer (RAFT) polymerization. P(DEGMA-co-OEGMA)-b-PNIPAAm copolymers showed two response temperatures at 33 and 43 °C in an aqueous solution forming stable aggregates at 37 °C. In contrast, P(DEGMA-co-OEGMA)-b-P(NIPAAm-co-BA) copolymers showed aggregation below room temperature due to the shift in response temperature provoked by the presence of hydrophobic butyl acrylate (BA) units, and shrinkage upon heating up to body temperature, while maintaining the second response temperature above 40 °C. The terminal trithiocarbonate group of the block copolymers was modified to a thiol functionality and used to stabilize gold nanorods (GNRDs) via the “grafting to” approach. The Localized Surface Plasmon Resonance (LSPR) absorption band of GNRDs with an aspect ratio of 3.9 (length/diameter) was located at 820 nm after surface grafting with block copolymers showing a hydrodynamic diameter of 160 nm at 37 °C. On the other hand, the stability of the P(DEGMA-co-OEGMA)-b-PNIPAAm@GNRDs and P(DEGMA-co-OEGMA)-b-P(NIPAAm-co-BA)@GNRDs nanohybrids was monitored for 8 days; where the LSPR absorption band did not shift or show any broadening. Aqueous dispersed nanohybrids were irradiated with a near-infrared laser (300 mW), where the temperature of the surroundings increased 16 °C after 16 min, where conditions for no precipitation were determined. These tailored temperature-responsive nanohybrids represent interesting candidates to develop drug nanocarriers for photo-thermal therapies. Full article

The potential antimicrobial and antibiofouling properties of previously synthesized PEG/NiPAAm interpenetrated polymer networks (IPNs) were investigated against three of the most common bacteria (E. coli, S. aureus, and S. epidermidis). The main goal was to evaluate the material’s biocompatibility and determine its potential use as an antifouling component in medical devices. This was intended to provide an alternative option that avoids drug usage as the primary treatment, thus contributing to the fight against antimicrobial resistance (AMR). Additionally, characterization and mechanical testing of the IPN were carried out to determine its resistance to manipulation processes in medical/surgical procedures. IPNs with different NiPAAm ratios exhibited excellent cytocompatibility with BALB/3T3 murine fibroblast cells, with cell viability values of between 90 and 98%. In addition, the results regarding the adsorption of albumin as a model protein showed a nearly constant adsorption percentage of almost zero. Furthermore, the bacterial inhibition tests yielded promising results, demonstrating effective pathogen growth inhibition after 48 h. These findings suggest the material’s suitability for use in biomedical applications. Full article

Miscarriage is defined as the loss of a pregnancy before 24 weeks and administration of progesterone in pregnancy has considerably decreased the risk of premature birth. Progesterone (PGT) starting from the luteal phase stabilizes pregnancy, promotes differentiation of the endometrium, and facilitates the implantation of the embryo. Within the present study, novel hybrid hydrogels based on chitosan methacrylate (CHT), hyaluronic acid (HA), and poly(N-isopropylacrylamide) (PNIPAAm) for vaginal delivery of progesterone were evaluated. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) for structural identity assessment and evaluation of their morphological aspects. The ability to swell, the release capacity, enzymatic degradation, cytotoxicity, and mucoadhesion were also reported. The characterized hydrogels demonstrated mucoadhesive properties in contact with the vaginal tissue of swine and bovine origin as substrates, and biodegradability and controlled release in a simulated vaginal environment. Cytocompatibility tests confirmed the ability of the hydrogels and progesterone to support cell viability and growth. The results showed pH-dependent behavior, controlled drug release, good cytocompatibility, and mucoadhesive properties. The hydrogels with higher chitosan amounts demonstrated better bioadhesive properties. This study provides insights into the potential of these hydrogels for the controlled vaginal delivery of progesterone, with promising therapeutic effects and no cytotoxicity observed. The experimental results indicated that a composition with a moderate content of PNIPAAm was suitable for the controlled delivery of progesterone. Full article

The thermo-responsive behavior of Poly(N-isopropylacrylamide) makes it an ideal candidate to easily embed cells and allows the polymer mixture to be injected. However, P(NiPAAm) hydrogels possess minor mechanical properties. To increase the mechanical properties, a covalent bond is introduced into the P(NIPAAm) network through a biocompatible thiol-ene click-reaction by mixing two polymer solutions. Co-polymers with variable thiol or acrylate groups to thermo-responsive co-monomer ratios, ranging from 1% to 10%, were synthesized. Precise control of the crosslink density allowed customization of the hydrogel’s mechanical properties to match different tissue stiffness levels. Increasing the temperature of the hydrogel above its transition temperature of 31 °C induced the formation of additional physical interactions. These additional interactions both further increased the stiffness of the material and impacted its relaxation behavior. The developed optimized hydrogels reach stiffnesses more than ten times higher compared to the state of the art using similar polymers. Furthermore, when adding cells to the precursor polymer solutions, homogeneous thermo-responsive hydrogels with good cell viability were created upon mixing. In future work, the influence of the mechanical micro-environment on the cell’s behavior can be studied in vitro in a continuous manner by changing the incubation temperature. 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

Self-healing, thermoresponsive hydrogels with a triple network (TN) were obtained by copolymerizing N-isopropyl acryl amide (NiPAAm) with polyvinyl alkohol (PVA) functionalized with methacrylic acid and N,N′-methylene bis(acryl amide) crosslinker in the presence of low amounts (<1 wt.%) of tannic acid (TA). The final gels were obtained by crystalizing the PVA in a freeze-thaw procedure. XRD, DCS, and SEM imaging indicate that the crystallinity is lower and the size of the PVA crystals is smaller at higher TA concentrations. A gel with 0.5 wt.% TA has an elongation at a break of 880% at a tension of 1.39 MPa. It has the best self-healing efficiency of 81% after cutting and losing the chemical network. Step-sweep strain experiments show that the gel has thixotropic properties, which are related to the TA/PVA part of the triple network. The low amount of TA leaves the gel with good thermal responsiveness (equilibrium swelling ratio of 13.3). Swelling-deswelling loop tests show enhanced dimensional robustness of the hydrogel, with a substantial constancy after two cycles. Full article

Thermoresponsive chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) copolymers of different composition were synthesized by free-radical polymerization of chitosan (CS) and N-isopropylacrylamide (NIPAAm) in aqueous solution using potassium persulfate (PPS) as an initiator. By changing the molar ratio of CS:NIPAAm from 1:0.25 to 1:10 graft copolymers with a CS backbone and different amounts of PNIPAM side chains were prepared. The chemical structure of the obtained CS-g-PNIPAAm copolymers was confirmed by FTIR and ¹H NMR spectroscopy. ¹H NMR spectra were also used to calculate the content of attached PNIPAAm side chains. Moreover, the lower critical solution temperature (LCST) behavior of synthesized copolymers was assessed by cloud point, differential scanning calorimetry and particle size measurements. The aqueous solutions of copolymers containing ≥12 molar percent of PNIPAAm side chains demonstrated LCST behavior with the phase separation at around 29.0–32.7 °C. The intensity of thermoresponsiveness depended on the composition of copolymers and increased with increasing content of poly(N-isopropylacrylamide) moieties. The synthesized thermoresponsive chitosan-graft-poly(N-isopropylacrylamide) copolymers could be potentially applied in drug delivery systems or tissue engineering. Full article

Curcumin, an active ingredient in turmeric, has various biological activities, but its low solubility and limited bioavailability hinder its therapeutic use. To address this, we created dual pH- and thermo-sensitive nanogels (NGs) from poly-N-isopropylacrylamide (PNIPAm) and polyacrylamide (PAAm) [P(NIPAAm-co-AAm) NGs] for delivering curcumin (Cur). We characterized the NGs using various techniques and found them to be biocompatible and low in toxicity. We conducted in vitro experiments to demonstrate the pH- and temperature-sensitive loading and release of Cur by controlling the swelling and deswelling of the NGs. The PNIPAm-co-PAAm copolymer we synthesized showed ~65% Cur loading. The NGs’ zeta potential decreased with increasing pH, and they underwent a phase transition at 40 °C with concentration-dependent properties. Almost 100% of Cur was released from the NGs after four hours at pH 5.5 and 40 °C. Therefore, these newly synthesized NGs have the potential for solid-tumor-targeted therapy by releasing the drug based on physical stimuli such as pH and temperature. Full article

The development of dual-stimuli-responsive hydrogels attracts much research interest owing to its unique stimuli-responsive characteristics. In this study, a poly-N-isopropyl acrylamide-co-glycidyl methacrylate-based copolymer was synthesized by incorporating N-isopropyl acrylamide (NIPAm) and a glycidyl methacrylate (GMA) monomer. The synthesized copolymer, pNIPAm-co-GMA was further modified with L-lysine (Lys) functional units and further conjugated with fluorescent isothiocyanate (FITC) to produce a fluorescent copolymer pNIPAAm-co-GMA-Lys hydrogel (HG). The in vitro drug loading and dual pH- and temperature-stimuli-responsive drug release behavior of the pNIPAAm-co-GMA-Lys HG was investigated at different pH (pH 7.4, 6.2, and 4.0) and temperature (25 °C, 37 °C, and 45 °C) conditions, respectively, using curcumin (Cur) as a model anticancer drug. The Cur drug-loaded pNIPAAm-co-GMA-Lys/Cur HG showed a relatively slow drug release behavior at a physiological pH (pH 7.4) and low temperature (25 °C) condition, whereas enhanced drug release was achieved at acidic pH (pH 6.2 and 4.0) and higher temperature (37 °C and 45 °C) conditions. Furthermore, the in vitro biocompatibility and intracellular fluorescence imaging were examined using the MDA-MB-231 cell line. Therefore, we demonstrate that the synthesized pNIPAAm-co-GMA-Lys HG system with temperature- and pH-stimuli-responsive features could be promising for various applications in biomedical fields, including drug delivery, gene delivery, tissue engineering, diagnosis, antibacterial/antifouling material, and implantable devices. Full article

In a previous study, we presented an empirical law for the magnetorheological effect of nanocomposite hydrogels with magnetite microparticles derived from rheological data. In order to understand the underlying processes, we employ computed tomography for structure analysis. This allows the evaluation of the translational and rotational movement of the magnetic particles. Gels with 10% and 3.0% magnetic particle mass content are investigated at three degrees of swelling and at different magnetic flux densities in steady states by means of computed tomography. Since a temperature-controlled sample-chamber is difficult to implement in a tomographic setup, salt is used to deswell the gels instead. Based on the findings of the particle movement, we propose a mechanism using an energy-based approach. This leads to a theoretical law that shows the same scaling behavior as the previously found empirical law. Full article

Hydrogels are functional smart materials which can be tailored by modifying their chemical composition. Further functionalization can be achieved by incorporating magnetic particles into the gel matrix. In this study, a hydrogel with magnetite micro-particles is synthesized and characterized by rheological measurements. Inorganic clay is used as the crosslinking agent, which additionally prevents the sedimentation of the micro-particles during the synthesis of the gel. The mass fractions for the magnetite particles in the synthesized gels range from 10% to 60% in the initial state. Rheological measurements are performed in different degrees of swelling using temperature as a stimulus. The influence of a homogeneous magnetic field is analyzed by a step-wise activation and deactivation during dynamic mechanical analysis. For the evaluation of the magnetorheological effect in the steady states a procedure is developed, which takes occurring drift effects into account. Using the magnetic flux density, the particle volume fraction and the storage modulus as independent parameters, a general product approach is deployed for a regression analysis of the dataset. In the end, an empirical law for the magnetorheological effect in nanocomposite hydrogels can be found. Full article