Injectable glycol chitosan thermogel formulation for efficient inner ear drug delivery.

We prepared a new injectable thermogel to enhance the efficiency of inner ear delivery of dexamethasone (DEX). Hexanoyl glycol chitosan (HGC) was synthesized and evaluated as an amphiphilic thermogel (Tgel ~ 32 °C) for use as a solubilizing agent as well as an injectable carrier for intratympanic delivery of the hydrophilic and hydrophobic forms of DEX. Various thermogel formulations with different drug types and concentrations were prepared, and their physicochemical and thermogelling properties were characterized by 1H NMR, ATR-FTIR, and rheometer. They exhibited versatile release kinetics from several hours to more than 2 weeks, depending on drug type and concentration. Our formulations further showed good residual stability for more than 21 days without any cytotoxicity or inflammation in the middle and inner ear and could deliver a considerably high drug concentration into the inner ear. Therefore, HGC thermogel has great potential as an effective and safe formulation for inner ear drug delivery.

Freeze-thaw and solvent-exchange strategy to generate physically cross-linked organogels and hydrogels of curdlan with tunable mechanical properties.

Physical gels from natural polysaccharides present the advantage of no toxic cross-linking agents and no chemical modification during preparation. Herein, novel physical gels, transparent organogels and opaque hydrogels from the microorganism-derived (1,3)-ß-D-glucan of curdlan were prepared in dimethyl sulfoxide (DMSO) using the freeze-thaw technique, followed by a solvent-exchange strategy with water. The mechanical and structural properties of these gels were investigated by rheology, scanning electron microscopy, attenuated total reflection infrared spectroscopy, wide-angle X-ray diffraction and small-angle X-ray scattering. Gelation mechanisms and intermolecular interaction models have also been proposed. The good solvent DMSO serves as both a crosslinker and a pore-foaming agent in organogels. The reversible macromolecular conformation changes and phase separation of curdlan endow the gels with reversible transparency, volume change and tunable mechanical strength. The new design strategy of facile preparation and performance tuning provides a platform for developing new organogels and sterile hydrogels of curdlan.

Lignocellulosic nanofibril aerogel via gas phase coagulation and diisocyanate modification for solvent absorption.

Cellulose-based aerogels are considered to be carriers that can absorb oils and organic solvents owing to the merits of low density and high surface area. However, the natural hydrophility and poor mechanical strength often obstruct their widespread applications. In this work, Miscanthus-based dual cross-linked lignocellulosic nanofibril (LCNF) aerogels were prepared by gas phase coagulation and methylene diphenyl dissocyanate (MDI) modification. Due to physical and chemical cross-linking strategies, the optimally 4 M-LCNF aerogels had high surface area of 157.9 m2/g, water contact angle of 138.1°, and enhanced compression properties. Moreover, the modified aerogels exhibited absorption performance for various organic solvents, and the maximal absorption capacity of chloroform was 42 g/g aerogel. Because LCNF was directly produced from Miscanthus without using bleaching reagents, this research provided a more sustainable methodology to utilize lignocelluloses to design robust aerogels to deal with the leakage of oil and organic solvents in industrial applications.

Sol-gel-derived hard coatings from tetraethoxysilane and organoalkoxysilanes bearing zwitterionic and isothiazolinone groups and their antifouling behaviors.

Current environmentally friendly marine antifouling (AF) coatings are mainly polymeric with a relatively low hardness. Hard sol-gel-derived AF coatings for underwater robot-cleaning are seldom used. In this work, two new organoalkoxysilanes, i.e., (N-methoxyacylethyl)-3-aminopropyltriethoxysilane and 2-(2-hydroxy-3-(3-(trimethoxysilyl)propoxy)propyl)benzo[d]isothiazol-3(2H)-one, were synthesized by a facile method. These two precursors were used with tetraethoxysilane (TEOS) to produce three series of hybrid AF coatings with zwitterionic group (Z-χ), antibacterial group (1,2-benzisothiazolin-3-one) (A-χ) and zwitterionic and antibacterial groups (S-χ) by a sol-gel process. The hardness of the coatings was measured using a pencil hardness tester and the AF behaviors of the coatings were examined by laboratory and field assays. A pencil hardness up to 5 H was achieved and slight deterioration was observed after 9 months of immersion in artificial seawater for the A-χ and S-χ coatings at a sufficiently high TEOS content. A synergistic effect between the zwitterion and antimicrobial agents existed but was not obvious. A higher TEOS content led to a higher hardness and better AF performance regardless of the type of AF group. Even with the same biofilm formation after field assay, coatings with a higher TEOS content exhibited a better resistance to mussel settlement.

Fluorescence response mechanism of green synthetic carboxymethyl chitosan-Eu3+ aerogel to acidic gases.

Industrial waste acidic gases are huge hazards to the environment and human health, so a material that can detect and remove them is needed. In this paper, CM chitosan-Eu3+ fluorescence aerogel was prepared via a green method by combining the carboxymethyl chitosan biomass polymer with Eu3+ ions, the structure and properties of this aerogel were characterized by SEM, TG, and stress-strain curves. The coordination of Eu3+ ions and carboxymethyl chitosan was analyzed with XPS and the difference in luminescence intensity of aerogel prepared at different pH values was analyzed. The monitoring of the aerogels revealed different responses to different acidic gases, and the fluorescence intensity of the aerogel showed a linear decrease with the adsorbed hydrogen chloride gas (HCl), while acetic acid gas (HAc) enhanced fluorescence. The adsorption system of the CM chitosan-Eu3+ aerogel was simulated using pseudo-second-order kinetics, which showed that the maximum adsorption capacity of HCl is 9.16 mmol/g. The different response mechanisms of HCl and HAc gas were analyzed with FT-IR, fluorescence lifetime imaging and Judd-Ofelt theory. This fluorescence aerogel was found to have potential applications in ensuring industrial production safety.

Lead zirconate titanate aerogel piezoelectric composite designed with a biomimetic shell structure for underwater acoustic transducers.

In this study, we used lead zirconate titanate (PZT) aerogels prepared by a solvothermal assisted sol-gel method as raw materials to synthesize PZT aerogel/PVDF composite coatings and PZT aerogel sintered sheets through natural annealing and PVDF composite and hot pressing, respectively, and then combined them with the design principle of a biomimetic shell structure to prepare an alternate coating/sheet structured PZT aerogel piezoelectric composite with natural distinguished mechanical properties. It had excellent piezoelectric properties with a piezoelectric coefficient d33 of 435.15 pC N-1 and d31 of -144.55 pC N-1, excellent electromechanical coupling properties with a planar electromechanical coupling coefficient of 60.14%, low dielectric loss of 0.76% at 40 Hz and low density of 3.04 g cm-3. When used as the piezoelectric material in underwater acoustic transducers (UATs), compared with all kinds of piezoelectric ceramics, it achieved higher piezoelectric and comprehensive mechanical properties, lower dielectric loss, lower density, and electromechanical coupling properties similar to that of Pb-containing piezoelectric ceramics, thus showing extremely promising application prospects in UATs.

Production of nanocellulose gels and films from invasive tree species.

Wood from invasive tree species Acacia dealbata and Ailanthus altissima was used to produce high value-added nanocellulose. Firstly, bleached pulps were produced from the wood of these tree species after kraft cooking. Afterwards, the resultant pulps were pre-treated by TEMPO-mediated oxidation (Acacia dealbata) or enzymatic hydrolysis (Ailanthus altissima) followed by high-pressure homogenization. Hydrogels were obtained and characterized for their main physical and chemical properties, including rheology measurements. After freeze-drying, the surface properties of the materials were evaluated by inverse gas chromatography. Results showed that nano/micro fibrils could be obtained from the wood of these invasive species. Rheometry studies showed that Acacia-TEMPO cellulose nanofibrils form strong gels with high yield stress point and viscosities (reaching ca. 100,000 Pa·s). Additionally, the surfaces of the obtained nanocelluloses showed a dispersive component of the surface energy near 40 mJ/m2 and a prevalence of the Lewis acidic character over the basic one, as typical for cellulose-based materials. Finally, films with good mechanical and optical properties could be obtained from the cellulose hydrogels. Acacia-TEMPO film (produced by filtration/hot pressing) showed a tensile strength of 79 MPa, Young's modulus of 7.9 GPa, and a transparency of 88%. The water vapor barrier, however, was modest (permeability of 4.9 × 10-6 g/(Pa·day·m)).

Tailoring Chitosan/LTA Zeolite Hybrid Aerogels for Anionic and Cationic Dye Adsorption.

Chitosan (CS) is largely employed in environmental applications as an adsorbent of anionic dyes, due to the presence in its chemical structure of amine groups that, if protonated, act as adsorbing sites for negatively charged molecules. Efficient adsorption of both cationic and anionic dyes is thus not achievable with a pristine chitosan adsorbent, but it requires the combination of two or more components. Here, we show that simultaneous adsorption of cationic and anionic dyes can be obtained by embedding Linde Type A (LTA) zeolite particles in a crosslinked CS-based aerogel. In order to optimize dye removal ability of the hybrid aerogel, we target the crosslinker concentration so that crosslinking is mainly activated during the thermal treatment after the fast freezing of the CS/LTA mixture. The adsorption of isotherms is obtained for different CS/LTA weight ratios and for different types of anionic and cationic dyes. Irrespective of the formulation, the Langmuir model was found to accurately describe the adsorption isotherms. The optimal tradeoff in the adsorption behavior was obtained with the CS/LTA aerogel (1:1 weight ratio), for which the maximum uptake of indigo carmine (anionic dye) and rhodamine 6G (cationic dye) is 103 and 43 mg g-1, respectively. The behavior observed for the adsorption capacity and energy cannot be rationalized as a pure superposition of the two components, but suggests that reciprocal steric effects, chemical heterogeneity, and molecular interactions between CS and LTA zeolite particles play an important role.

Intranasal In Situ Gel of Apixaban-Loaded Nanoethosomes: Preparation, Optimization, and In Vivo Evaluation.

The present study was conducted to formulate ethosomal thermoreversible in situ gel of apixaban, an anticoagulant drug, for nasal delivery. Ethosomes were formed, of lecithin, cholesterol, and ethanol, by using thin-film hydration method. The prepared ethosomes were characterized by Zetasizer, transmission electron microscope, entrapment efficiency, and in vitro study. The selected ethosomal formula (API-ETHO2) was incorporated in gel using P407 and P188 as thermoreversible agents and carbopol 934 as mucoadhesive agent. Box-Behnken design was used to study the effect of independent variables (concentration of P407, P188, and carbopol 934) on gelation temperature, mucoadhesive strength, and in vitro cumulative percent drug released at 12h (response variables). The optimized formulation was subjected to compatibility study, ex vivo permeation, histopathological examination for the nasal mucosa, and in vivo study. API-ETHO2 was spherical with an average size of 145.1±12.3 nm, zeta potential of -20±4 mV, entrapment efficiency of 67.11%±3.26, and in vitro % release of 79.54%±4.1. All gel formulations exhibited an acceptable pH and drug content. The optimum gel offered 32.3°C, 1226.3 dyne/cm2, and 53.50% for gelation temperature, mucoadhesive strength, and in vitro percent released, respectively. Apixaban ethosomal in situ gel evolved higher ex vivo permeation (1.499±0.11 µg/cm2h) through the nasal mucosa than pure apixaban gel. Histopathological study assured that there is no necrosis or tearing of the nasal mucosa happened by ethosomal gel. The pharmacokinetic parameters in rabbit plasma showed that intranasal administration of optimized API-ethosomal in situ gel achieved higher Cmax and AUC0-∞ than unprocessed API nasal gel, nasal suspension, and oral suspension. The ethosomal thermoreversible nasal gel established its potential to improve nasal permeation and prolong anticoagulant effect of apixaban.

Spatiotemporal Control of Supramolecular Polymerization and Gelation of Metal-Organic Polyhedra.

In coordination-based supramolecular materials such as metallogels, simultaneous temporal and spatial control of their assembly remains challenging. Here, we demonstrate that the combination of light with acids as stimuli allows for the spatiotemporal control over the architectures, mechanical properties, and shape of porous soft materials based on metal-organic polyhedra (MOPs). First, we show that the formation of a colloidal gel network from a preformed kinetically trapped MOP solution can be triggered upon addition of trifluoroacetic acid (TFA) and that acid concentration determines the reaction kinetics. As determined by time-resolved dynamic light scattering, UV-vis absorption, and 1H NMR spectroscopies and rheology measurements, the consequences of the increase in acid concentration are (i) an increase in the cross-linking between MOPs; (ii) a growth in the size of the colloidal particles forming the gel network; (iii) an increase in the density of the colloidal network; and (iv) a decrease in the ductility and stiffness of the resulting gel. We then demonstrate that irradiation of a dispersed photoacid generator, pyranine, allows the spatiotemporal control of the gel formation by locally triggering the self-assembly process. Using this methodology, we show that the gel can be patterned into a desired shape. Such precise positioning of the assembled structures, combined with the stable and permanent porosity of MOPs, could allow their integration into devices for applications such as sensing, separation, catalysis, or drug release.

Synthesis of a green bigel using cottonseed oil/cannabis oil/alginate/ferula gum for quercetin release: Synergistic effects for treating infertility in rats.

Although therapeutic effect of quercetin (Quer) was reported on non-alcoholic fatty liver disease (NAFLD), destructive effects have been shown on male fertility due to its pro-oxidative properties. On the other hand, NAFLD impairs germ cells to produce sperm and leads to male infertility. Herein, a biocompatible and green bigel was designed for Quer delivery to prevent infertility induced by NAFLD as the increasing complications. Bigels were prepared using cottonseed oil/cannabis oil/alginate/ferula gum and optimized by the mixture design method. NAFLD was induced by 58% of dietary calorie as lard and 42 g/l fructose for 16 weeks in Sprague-Dawley rats. So on animals received 2 mg/kg Quer loaded on bigels, free bigels, or free Quer for 45 days as daily gavage. Semen was analyzed, followed by the assessment of DNA integrity. Count, motility, and normal morphology reached the healthy control group at the bigel-Quer-treated one. Moreover, all of these parameters were significantly higher in the bigel-Quer group than the Quer and bigel, alone. The percent of sperms with head and tail abnormality decreased considerably in the bigel-Quer group compared with the Quer, free bigel, and NAFLD groups. Serum testosterone levels significantly increased and reached the healthy control group in the bigel-Quer group. DNA fragmentation of sperm significantly decreased in the bigel-Quer group (p < 0.05). The bigel showed synergistic effects with Quer for treating infertility in rats with NAFLD.

Serum Protein Adsorption Modulates the Toxicity of Highly Positively Charged Hydrogel Surfaces.

Hydrogels formed from peptide self-assembly are a class of materials that are being explored for their utility in tissue engineering, drug and cell delivery, two- and three-dimensional cell culture, and as adjuvants in surgical procedures. Most self-assembled peptide gels can be syringe-injected in vivo to facilitate the local delivery of payloads, including cells, directly to the targeted tissue. Herein, we report that highly positively charged peptide gels are inherently toxic to cells, which would seem to limit their utility. However, adding media containing fetal bovine serum, a common culture supplement, directly transforms these toxic gels into cytocompatible materials capable of sustaining cell viability even in the absence of added nutrients. Multistage mass spectrometry showed that at least 40 serum proteins can absorb to a gel's surface through electrostatic attraction ameliorating its toxicity. Further, cell-based studies employing model gels having only bovine serum albumin, fetuin-A, or vitronectin absorbed to the gel surface showed that single protein additives can also be effective depending on the identity of the cell line. Separate studies employing these model gels showed that the mechanism(s) responsible for mitigating apoptosis involve both the pacification of gel surface charge and adsorbed protein-mediated cell signaling events that activate both the PI3/Akt and MAPK/ERK pathways which are known to facilitate resistance to stress-induced apoptosis and overall cell survival.

In situ reduced graphene-based aerogels embedded with gold nanoparticles for real-time humidity sensing and toxic dyes elimination.

Hybrid aerogels are promising candidates for energy storage, biosensing, and medical applications, but the conventional fabrication methods, being time-consuming and complex, limit their widespread utilization. The critical issues affecting their functionality include the un-controllable particle dispersity, loading of active materials, and the porosity. We report a simple and efficient method to synthesize in situ reduced Au nanoparticles@graphene (Au@graphene) hybrid aerogel using near-infrared radiation (NIR), resulting the uniform loading of well-dispersed Au nanoparticles (Au-NPs) as well as in situ reduction of graphene oxide (GO) with enhanced conductivity. The concentration of iso-propylacrylamide and GO can be adjusted to control the aerogel pore size during the freeze-drying process. Reduction of HAuCl4 and GO to high extent under NIR light was confirmed with advanced characterization techniques. Density functional theory based calculations with generalized gradient-corrected functional (GGA/PW91) in the hybrid aerogel system, and dnd basis sets are used for the confirmation of possible interactions between the GO, Au-NPs, and the polymer. The as-designed highly porous and conductive aerogel shows an excellent humidity response (30-97%) and successfully removes the methylene blue pollutant from the aqueous solution to a high extent (90%). Therefore, Au@graphene hybrid aerogel is potentially an exciting candidate for a wide range of applications in the humidity sensing and biomedical disease detection.

A facile synthesis of graphene oxide/locust bean gum hybrid aerogel for water purification.

Graphene oxide/locust bean gum (GO/LBG) aerogels, synthesized in an ice crystal template without using any chemical modifiers, were used for the treatment of water pollution. Various characterization results showed that GO/LBG aerogel exhibited a network-like three-dimensional (3D) structure with large specific surface area. The adsorption data revealed that GO/LBG aerogels with GO/LBG mass ratio of 1:4 (GO/LBG-1 aerogels) exhibited more prominent adsorption properties for Rhodamine-B (RhB, 514.5 mgg-1) than Indigo Carmine (IC, 134.6 mgg-1). Simultaneously, GO/LBG-1 aerogels could selectively remove RhB from a binary mixed solution of RhB-IC dyes. Furthermore, GO/LBG-1 aerogels also displayed excellent reusability and could still reach 92.4 % after ten cycles. Based on the above results, GO/LBG-1 aerogel could be considered as an ideal adsorbent with potential application value for removing water-soluble RhB from wastewater.

Aerogels based on corn starch as carriers for pinhão coat extract (Araucaria angustifolia) rich in phenolic compounds for active packaging.

The objective of this study was to produce renewable aerogels from native and anionic corn starches loaded with pinhão coat extract (PCE) with water absorbent capacity, antioxidant activity and controlled release of phenolic compounds in a hydrophilic food simulant media. Starch aerogels were produced with different concentrations of PCE, 5 and 10%, and evaluated for FT-IR spectra, relative crystallinity, thermal properties, water absorption capacity (WAC), density, antioxidant activity and in vitro release. Thermal stability of the compounds was improved by the incorporation of PCE. The aerogels presented high WAC of 541 to 731% and low-density values of 0.03 g.cm-1. The highest inhibition of DPPH and ABTS radicals was presented to anionic starch aerogels with 10% PCE rendering 26% of inhibition of ABTS and 24% of DPPH. The maximum in vitro releases for native and anionic starch aerogels with 5% of PCE were 28.70 and 29.44%, respectively, and for aerogels with 10% of PCE they were 34.27 and 35.94%, respectively. The anionic starch aerogels had the highest amount of phenolic compounds released when compared to the native starch aerogels. The starch-based bioactive aerogels showed potential to be applied in food packaging as water absorbent and as a carrier of phenolic compounds.

The role of alkali in sweet potato starch-Mesona chinensis Benth polysaccharide gels: Gelation, rheological and structural properties.

According to the Chinese traditional black jelly production process, a critical step to ensure the quality of jelly is to add alkali to it. In this study, the effects of sodium carbonate (Na2CO3) and sodium bicarbonate (NaHCO3) on the pasting, rheological, textural, and structural properties of sweet potato starch (SPS)-Mesona chinensis Benth polysaccharide (MCP) gels were evaluated. Adding Na2CO3 at low concentration reduced the final viscosity (FV) of SPS-MCP gels, whereas adding it at a high concentration increased the FV. Adding NaHCO3 can increase the FV of SPS-MCP gels in a concentration-dependent manner. Rheological results indicated that adding NaHCO3 at a low concentration decreased the storage modulus of SPS-MCP gels, whereas adding it at a high concentration increased the storage modulus. The storage modulus of SPS-MCP gels increased with increasing concentration of NaHCO3. The addition of Na2CO3 and NaHCO3 improved the textural properties of SPS-MCP gels and decreased the water mobility. Infrared results indicated that adding alkali can enhance the hydrogen bonding between SPS and MCP. Scanning electron microscopy results suggested that alkali can reduce the size of gels, and make the structure more compact.

Long-term antibacterial composite via alginate aerogel sustained release of antibiotics and Cu used for bone tissue bacteria infection.

Bone related-bacterial diseases including wound infections and osteomyelitis (OM) remain a serious problem accompanied with amputation in most severe cases. In this work, we report an exceptional effective antibacterial alginate aerogel, which consists of tigecycline (TGC) and octahedral Cu crystal as an organo-inorganic synergy platform for antibacterial and local infection therapy applications. The alginate aerogel could greatly prolong the release of copper ions and maintain effective antibacterial concentration over 18 days. The result of in-vitro experiments demonstrated that the alginate aerogel has an exceptional effective function on antibacterial activity. Cytotoxicity tests indicated that the alginate aerogel has low biological toxicity (average cell viability >75%). These remarkable results suggested that the alginate aerogel exhibits great potential for the treatment of OM, and has a prosperous future of application in bone tissue engineering.

Nanostructured Gels for Energy and Environmental Applications.

Nanostructured gels have emerged as an attractive functional material to innovate the field of energy, with applications ranging from extraction and purification to nanocatalysts with unprecedented performance. In this review we discuss the various classes of nanostructured gels and the most recent advancements in the field with a perspective on future directions of this challenging area.

Sustainable drug release from polycaprolactone coated chitin-lignin gel fibrous scaffolds.

Non-healing wounds have placed an enormous stress on both patients and healthcare systems worldwide. Severe complications induced by these wounds can lead to limb amputation or even death and urgently require more effective treatments. Electrospun scaffolds have great potential for improving wound healing treatments by providing controlled drug delivery. Previously, we developed fibrous scaffolds from complex carbohydrate polymers [i.e. chitin-lignin (CL) gels]. However, their application was limited by solubility and undesirable burst drug release. Here, a coaxial electrospinning is applied to encapsulate the CL gels with polycaprolactone (PCL). Presence of a PCL shell layer thus provides longer shelf-life for the CL gels in a wet environment and sustainable drug release. Antibiotics loaded into core-shell fibrous platform effectively inhibit both gram-positive and -negative bacteria without inducting observable cytotoxicity. Therefore, PCL coated CL fibrous gel platforms appear to be good candidates for controlled drug release based wound dressing applications.

Bioinspired Color-Changeable Organogel Tactile Sensor with Excellent Overall Performance.

Inspired by chameleons' structural color regulation capability, a simple, but effective, swelling method is proposed for the first time to prepare an ionic polyacrylamide (PAAm) organogel for simultaneous tactile sensing and interactive color changing. The PAAm organogel obtained by swelling the PAAm scaffold in the dimethyl sulfoxide solution of organic electrochromic material (OECM) shows an extremely large stretchability with an elongation of 1600%, a supersoftness with a compressive modulus of 7.2 kPa, an excellent transmittance up to 90%, and a very fast response time of 0.5 s combined with the characteristic of interactive color changing. The PAAm organogel also suggests a universal design ability to tailor coloration spectra for tactile sensors via simply changing the type and content of OECM. The tactile sensor based on a PAAm organogel is capable of serving as a wearable device for precisely tracing human body motion performance and directly visualizing the stress distribution via interactive color changing capability. It is demonstrated that the swelling method proposed here is a simple and practical strategy to prepare ionic organogels with both piezo-resistive and electrochromic effects.