Gels, Volume 8, Issue 3 (March 2022) – 58 articles

In this study, we report the highly responsive chitosan-based chemically cross-linked nanomatrices, a nano-version of hydrogels developed through modified polymerization reaction for solubility improvement of poorly soluble drug simvastatin. The developed nanomatrices were characterized for solubilization efficiency, swelling studies, sol-gel analysis, in vitro drug release studies, DSC, FTIR, XRD, SEM, particle size analysis, and stability studies. An in vivo acute toxicity study was conducted on female Winstor rats, the result of which endorsed the safety and biocompatibility of the system. A porous and fluffy structure was observed under SEM analysis, which supports the great swelling tendency of the system that further governs the in vitro drug release. Zeta sizer analyzed the particle size in the range of 227.8 ± 17.8 nm. Nano sizing and grafting of hydrophilic excipients to the nanomatrices system explains this shift of trend towards the enhancement of solubilization efficiency, and, furthermore, the XRD results confirmed the amorphous nature of the system. FTIR and DSC analysis confirmed the successful grafting and stability to the system. The developed nanomatrices enhanced the release characteristics and solubility of simvastatin significantly and could be an effective technique for solubility and bioavailability enhancement of other BCS class-II drugs. Due to enhanced solubility, efficient method of preparation, excellent physico-chemical features, and rapid and high dissolution and bio-compatibility, the developed nanomatrices may be a promising approach for oral delivery of hydrophobic drugs. Full article

Geopolymer is a green non-metallic material with high strength and favorable properties in resistance to corrosion, fire, and high temperature, which makes it a potential substitute for Portland cement. The existing studies have primarily focused on the preparation of geopolymers using silico-alumina materials such as fly ash, red mud, metakaolin, volcanic ash, and blast furnace slag to develop geopolymers. This study explores the potential of using ultrafine calcined coal gangue and ground granulated blast furnace slag to develop a new geopolymer with the activation of a single activator (sodium hydroxide) or mixed activator (sodium hydroxide, liquid sodium silicate, and desulfurization gypsum). The setting time and strength of the geopolymers were investigated, followed by the mineral, functional groups, microstructure, and elements analyses using X-ray diffraction, Fourier transform infrared diffraction, scanning electron microscope, and energy dispersive spectrometer to elucidate the effect of different activators on geopolymers. The results showed that the optimum molarity of NaOH single activator was 2 mol/L, the initial setting time and final setting time were 37 min and 47 min, respectively, and the compressive and flexural strengths at 28 days were 23.2 MPa and 7.5 MPa. The optimal mixing ratio of the mixed activator was 6% desulfurization gypsum, 0.6 Na₂SiO₃ modulus, and 16% SS activator; the initial setting time and final setting time were 100 min and 325 min, respectively, and the compressive and flexural strengths at 28 days were 40.1 MPa and 7.8 MPa. The coal gangue geopolymers were mainly C–A–S–H, N–A-S-H, and C–N–A–S–H gels. The mixed activator tended to yield higher strengths than the single activator, the reason is that the hydration reaction was violent and produced more gels. Meanwhile, the relation between setting time and activator and the relation between strength and activator were also obtained, which provide theoretical support for predicting the setting time of coal gangue base polymer and the ratio of alkali activator for geopolymers with a certain strength. Full article

Strain hardening, i.e., the nonlinear elastic response of materials under load, is a physiological response of biological tissues to mechanical stimulation. It has recently been shown to play a central role in regulating cell fate. In this paper, we investigate the effect of temperature and polymer concentrations on the strain hardening of covalent hydrogels composed of pH-neutral soluble chitosans crosslinked with genipin. A series of highly acetylated chitosans with a fraction of acetylated units, F_A, in the range of 0.4–0.6 was synthesized by the homogeneous re-N-acetylation of a partially acetylated chitosan or the heterogeneous deacetylation of chitin. A chitosan sample with an F_A = 0.44 was used to prepare hydrogels with genipin as a crosslinker at a neutral pH. Time and frequency sweep experiments were then performed to obtain information on the gelling kinetics and mechanical response of the resulting hydrogels under small amplitude oscillatory shear. While the shear modulus depends on the chitosan concentration and is almost independent of the gel temperature, we show that the extent of hardening can be modulated when the gelling temperature is varied and is almost independent of the experimental conditions used to build the hydrogels (ex situ or in situ gelation). The overall effect is attributed to a subtle balance between the physical (weak) entanglements and covalent (strong) crosslinks that determine the mechanical response of highly acetylated chitosan hydrogels at large deformations. Full article

Owing to the potential of sodium as an alternative to lithium as charge carrier, increasing attention has been focused on the development of high-performance electrolytes for Na batteries in recent years. In this regard, gel-type electrolytes, which combine the outstanding ionic conductivity of liquid electrolytes and the safety of solid electrolytes, demonstrate immense application prospects. However, most gel electrolytes not only need a number of specific techniques for molding, but also typically suffer from breakage, leading to a short service life and severe safety issues. In this study, a supramolecular thixotropic ionogel electrolyte is proposed to address these problems. This thixotropic electrolyte is formed by the supramolecular self-assembly of D-gluconic acetal-based gelator (B8) in an ionic liquid solution of a Na salt, which exhibits moldability, a high ionic conductivity, and a rapid self-healing property. The ionogel electrolyte is chemically stable to Na and exhibits a good Na⁺ transference number. In addition, the self-assembly mechanism of B8 and thixotropic mechanism of ionogel are investigated. The safe, low-cost and multifunctional ionogel electrolyte developed herein supports the development of future high-performance Na batteries. Full article

Backfill mining is the only way to realize no-waste mining and create green mines, but complicated backfill mining technology, high mining costs, and low-production capacity greatly restrict its application in low-quality iron mines. To reduce the cost of iron ore backfill mining, a large number of low-cost green backfill cementing materials have been developed in China over the past 10 years. This paper first introduces the research and development of green cementitious materials using solid waste. Then, it points out the key technologies in the development of green filling cementing materials, reveals the hydration mechanism of green cementing materials through microscopic analysis and research, and optimizes the ratio of green cementing materials based on an orthogonal test. Finally, the development direction of green filling cementing materials is put forward: combining technology development with the filling mining method and filling process; taking the development route from technology to products and from products to commodities. To reduce the cost of filling mining and pursue the economic benefits of filling mining, a demonstration mine of tailings and green cementing materials is taken as the breakthrough point to comprehensively promote the development of iron ore full solid-waste filling mining technology and achieve its large-scale promotion and application. Full article

The self-assembly of carbohydrate-based low molecular weight gelators has led to useful advanced soft materials. The interactions of the gelators with various cations and anions are important in creating novel molecular architectures and expanding the scope of the small molecular gelators. In this study, a series of thirteen new C-2 carbamates of the 4,6-O-phenylethylidene acetal-protected D-glucosamine derivatives has been synthesized and characterized. These compounds are rationally designed from a common sugar template. All carbamates synthesized were found to be efficient gelators and three compounds are also hydrogelators. The resulting gels were characterized using optical microscopy, atomic force microscopy, and rheology. The gelation mechanisms were further elucidated using ¹H NMR spectroscopy at different temperatures. The isopropyl carbamate hydrogelator 7 formed hydrogels at 0.2 wt% and also formed gels with several tetra alkyl ammonium salts, and showed effectiveness in the creation of gel electrolytes. The formation of metallogels using earth-abundant metal ions such as copper, nickel, iron, zinc, as well as silver and lead salts was evaluated for a few gelators. Using chemiluminescence spectroscopy, the metal–organic xerogels showed enzyme-like properties and enhanced luminescence for luminol. In addition, we also studied the applications of several gels for drug immobilizations and the gels showed sustained release of naproxen from the gel matrices. This robust sugar carbamate-derived gelator system can be used as the scaffold for the design of other functional materials with various types of applications. Full article

In the current study, a pH sensitive intelligent hydroxypropyl–β–cyclodextrin-based polymeric network (HP-β-CD-g-MAA) was developed through a solution polymerization technique for site specific delivery of cytarabine in the colonic region. Prepared hydrogel formulations were characterized through cytarabine loading (%), ingredient’s compatibility, structural evaluation, thermal integrity, swelling pattern, release behavior and toxicological profiling in rabbits. Moreover, the pharmacokinetic profile of cytarabine was also determined in rabbits. New polymer formation was evident from FTIR findings. The percentage loaded into the hydrogels was in the range of 37.17–79.3%. Optimum swelling ratio of 44.56 was obtained at pH 7.4. Cytarabine release was persistent and in a controlled manner up to 24 h. In vitro degradation of hydrogels was more pronounced at intestinal pH as compared to acidic pH. Toxicity studies proved absence of any ocular, skin and oral toxicity, thus proving biocompatibility of the fabricated network. Hydrogels exhibited longer plasma half-life (8.75 h) and AUC (45.35 μg.h/mL) with respect to oral cytarabine solution. Thus, the developed hydrogel networks proved to be excellent and biocompatible cargo for prolonged and site-specific delivery of cytarabine in the management of colon cancer. Full article

The aim of the study was to develop and evaluate the Ginkgo biloba nanocomplex gel (GKNG) as a long-acting formulation for the wound healing potential. Pharmaceutical analysis showed an average particle size of 450.14 ± 36.06 nm for GKNG, zeta potential +0.012 ± 0.003 mV, and encapsulation efficiency 91 ± 1.8%. The rheological analysis also showed the optimum diffusion rate and viscosity needed for topical drug delivery. Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analysis further confirmed the success of GKNG. The in vivo study showed increments in the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) and a lower level of lipid peroxidation (MDA) after GKNG treatment. The GKNG group showed upregulations in collagen type I, as alpha 1 collagen (COL1A1), and collagen type IV, as alpha 1 collagen (COL4A1). Furthermore, the in vivo study showed increments in hydroxyproline, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta 1 (TGF-β1) after the GKNG. Additionally, GKNG effectively increased the wound contraction compared to GK gel and sodium alginate (SA) gel. Based on the in vitro and in vivo evaluation, GKNG effectively accelerated wound healing by modulation of antioxidant enzymes, collagens, angiogenic factors, and TGF-β1. Full article

Hydrogels play important roles in function materials, especially in wastewater treatment, that could solve the problems of microbial infections and dye pollutions. Herein, a natural glycyrrhetinic acid-derived gel was successfully constructed by forming hierarchical assemblies of the glycyrrhetinic acid derivatives (GA-O-09) with Cu²⁺. Interestingly, the GA-O-09/Cu²⁺ gel exhibited Cu²⁺-triggered shrinkage, which was helpful for spontaneous self-demolding through the shrinkage process with a precise amount of Cu²⁺. Moreover, the gel showed excellent antimicrobial activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentrations (MICs) at 2.5 μg/mL and 5.0 μg/mL, respectively. Furthermore, the resultant GA-O-09/Cu²⁺ gel showed an excellent performance in dyes removal; the adsorption capacity at equilibrium (q_e) could reach 82.91 mg/g according to a pseudo-second-order model, and it was better than most reported dye adsorbent materials. The experimental result suggested that the electrostatic interactions of the hydrogel with the cationic dyes and the hydrogel swelling were responsible for the possible dye removal mechanism of GA-O-09/Cu²⁺ gel. Therefore, our study holds the promise of a better future, for such a hydrogel could be used as an antibacterial and dye removal material. Full article

Mesenchymal stem cells (MSCs) possess immunomodulatory properties and capacity for endogenous regeneration. Therefore, MSC therapy is a promising treatment strategy for COVID-19. However, the cells cannot stay in the lung long enough to exert their function. The extracellular matrix from porcine bladders (B-ECM) has been shown not only to regulate cellular activities but also to possess immunoregulatory characteristics. Therefore, it can be hypothesized that B-ECM hydrogel could be an excellent scaffold for MSCs to grow and could anchor MSCs long enough in the lung so that they can exhibit their immunomodulatory functions. In this study, ECM degradation products and a co-culture system of MSCs and macrophages were developed to study the immunomodulatory properties of ECM and MSCs under septic conditions. The results showed that B-ECM degradation products could decrease pro-inflammatory and increase anti-inflammatory cytokines from macrophages. In an in vivo mimicking co-culture system, MSCs cultured on B-ECM hydrogel exhibited immunomodulatory properties at both gene and protein levels. Both B-ECM degradation products and MSC conditioned medium supported the wound healing of alveolar epithelial cells. The results from the study could offer a basis for investigation of immunomodulation by ECM and MSCs before conducting in vivo experiments, which could later be applied in regenerative medicine. Full article

The removal of arsenate ions from aqueous solutions at near-neutral pH was carried out using chitosan-magnetite (ChM) hydrogel beads in batch systems. Equilibrium isotherms and kinetic studies are reported. Obtained equilibrium and kinetic data were fitted to mathematical models, estimating model parameters by non-linear regression analysis. Langmuir model was found to best fit equilibrium data; a maximum adsorption capacity of 66.9 mg As/g was estimated at pH 7.0. Pseudo-first order kinetic model was observed to best fit kinetic data. The pH of the solution was observed to increase with increasing contact time, which is attributed to protonation of amine groups present in the hydrogel. Protonation of functional groups in the ChM sorbent yields a higher number of active sites for arsenate removal, being as this a process that can’t be overlooked in future applications of ChM hydrogel for the removal or arsenate ions. Chitosan-magnetite and ChM-arsenate interactions were determined by XPS. Arsenate removal using fixed-bed column packed with ChM was carried out, reporting a non-ideal behavior attributed to pH increase of the effluent caused by proton transfer to ChM hydrogels. Full article

Polymer gel is the most widely used plugging agent in profile control, whose formula and injected speed are very important process parameters. It is very significant to study the effect of shear rates on the dynamic gelation of polymer gel in porous media for selecting suitable formula and injection speed. Taking the phenol formaldehyde resin gel with static gelation time of 21 h in ampoule bottle as research objective, it was studied the dynamic gelation process and subsequent water flooding in porous media under different injected speeds by a circulated equipment. The results shown that final dynamic gelation time is 2.4 times longer than the static gelation time in porous media. The gel particles are formed and mainly accumulated in the near wellbore zone after dynamic gelation. Injection speed has little effect on the dynamic gelation time in porous media, but has a great effect on the gel strength. The effect of injection speed on dynamic gel strength is evaluated by established the quantitative relationship between shear rate and dynamic gel strength. According to subsequent water flooding results, gel particles have certain plugging capacity in the near wellbore zone. The plugging ability declines obviously with an increasing injection speed. The experimental results provide theoretical support for the successful application of polymer gel used in profile control. Full article

Micro- and nanogels are being increasingly used to encapsulate bioactive compounds. Their soft structure allows large loading capacity while their stimuli responsiveness makes them extremely versatile. In this work, the complexation of DNA with thermoresponsive microgels is presented. To this end, PEGylated charged microgels based on poly-N-isopropylacrylamide have been synthesized, allowing one to explore the electrostatics of the complexation. Cationic microgels complexate spontaneously by electrostatic attraction to oppositely charged DNA as demonstrated by electrophoretic mobility of the complexes. Then, Langmuir monolayers reveal an increased interaction of DNA with swollen microgels (20 °C). Anionic microgels require the presence of multivalent cations (Ca²⁺) to promote the complexation, overcoming the electrostatic repulsion with negatively charged DNA. Then again, Langmuir monolayers evidence their complexation at the surface. However, the presence of Ca²⁺ seems to induce profound changes in the interaction and surface conformation of anionic microgels. These alterations are further explored by measuring adsorbed films with the pendant drop technique. Conformational changes induced by Ca²⁺ on the structure of the microgel can ultimately affect the complexation with DNA and should be considered in the design. The combination of microstructural and surface properties for microgels offers a new perspective into complexation of DNA with soft particles with biomedical applications. Full article

Standard hydrogels prepared by free radical polymerization (FRP) have heterogeneous structures with a wide mesh size distribution, which affect their mechanical and separation properties. Recent research has identified four-armed poly(ethylene glycol) (tetra-PEG) as a solution to this problem. tetra-PEG gels with a homogeneous network can be prepared and applied as high-strength gels and cell-culture substrates by reacting two types of tetra-PEG with different reactive groups at the ends. In this study, we report a photoresponsive tetra-PEG that undergoes a phase transition from a sol to a gel state in response to light. tetra-PEGs containing cinnamoyl and maleimide groups at the ends of the four-armed chains were found to gel when exposed to light. The effects of polymer concentration and light irradiation time on the gelation of tetra-PEG containing photodimerization groups were investigated. The results showed that the elastic modulus of the gel increased with the increase in the light irradiation time. Full article

Hyaluronic acid (HA) was functionalized with a series of amino synthons (octylamine, polyethylene glycol amine, trifluoropropyl amine, rhodamine). Sodium hyaluronate (HAs) was first converted into its protonated form (HAp) and the reaction was conducted in DMSO by varying the initial ratio (−NH₂ (synthon)/COOH (HAp)). HA derivatives were characterized by a combination of techniques (FTIR, ¹H NMR, 1D diffusion-filtered ¹⁹F NMR, DOSY experiments), and degrees of substitution (DS_HA) varying from 0.3% to 47% were determined, according to the grafted synthon. Nanohydrogels were then obtained by ionic gelation between functionalized hyaluronic acids and chitosan (CS) and tripolyphosphate (TPP) as a cross-linker. Nanohydrogels for which HA and CS were respectively labeled by rhodamine and fluorescein which are a fluorescent donor-acceptor pair were subjected to FRET experiments to evaluate the stability of these nano-assemblies. Full article

To design a controlled drug release preparation based on a safe natural material, a Konjac glucomannan (KGM) mixture containing 16.0 w/w% calcium hydroxide (Ca(OH)₂) was ground in a planetary ball mill for 0–120 min. The mechanochemical effect on the physicochemical properties of the KGM ground product was investigated by Fourier-transform infrared spectroscopy (FT-IR), powder X-ray spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy, and drug release testing. The FT-IR spectra of the ground KGM indicated that the deacetylation reaction of KGM was accelerated in the Ca(OH)₂-containing sols by mechanochemical energy, and the degree of deacetylation of KGM was dependent on the grinding time. The time required for tablet disintegration of the KGM matrix tablets containing theophylline increased as the grinding time increased; therefore, drug release was sustained. The Higuchi plots of the matrix tablets obtained from KGM ground for 60–120 min exhibited good linearity because they maintained their gel matrix tablet shape during the release test. However, KGM tablets ground for 0–30 min exhibited nonlinear curves, which were caused by tablet disintegration. This suggests that drug release from the KGM matrix tablet can be freely controlled by the degree of mechanochemical treatment. Full article

Transarterial radioembolization (TARE) is an emerging treatment for patients with unresectable hepatocellular carcinoma (HCC). This study successfully developed radiometal-labeled chitosan microspheres (¹¹¹In/¹⁷⁷Lu-DTPA-CMS) with a diameter of 36.5 ± 5.3 μm for TARE. The radiochemical yields of ¹¹¹In/¹⁷⁷Lu-DTPA-CMS were greater than 90% with high radiochemical purities (>98%). Most of the ¹¹¹In/¹⁷⁷Lu-DTPA-CMS were retained in the hepatoma and liver at 1 h after intraarterial (i.a.) administration. Except for liver accumulation, radioactivity in each normal organ was less than 1% of the injected radioactivity (%IA) at 72 h after injection. At 10 days after injection of ¹⁷⁷Lu-DTPA-CMS (18.6 ± 1.3 MBq), the size of the hepatoma was significantly reduced by around 81%, while that of the rats in the control group continued to grow. This study demonstrated the effectiveness of ¹⁷⁷Lu-DTPA-CMS in the treatment of N1-S1 hepatoma. ¹¹¹In/¹⁷⁷Lu-DTPA-CMS have the potential to be a superior theranostic pair for the treatment of clinical hepatoma. Full article

Three-dimensional (3D) printing is well acknowledged to constitute an important technology in tissue engineering, largely due to the increasing global demand for organ replacement and tissue regeneration. In 3D bioprinting, which is a step ahead of 3D biomaterial printing, the ink employed is impregnated with cells, without compromising ink printability. This allows for immediate scaffold cellularization and generation of complex structures. The use of cell-laden inks or bio-inks provides the opportunity for enhanced cell differentiation for organ fabrication and regeneration. Recognizing the importance of such bio-inks, the current study comprehensively explores the state of the art of the utilization of bio-inks based on natural polymers (biopolymers), such as cellulose, agarose, alginate, decellularized matrix, in 3D bioprinting. Discussions regarding progress in bioprinting, techniques and approaches employed in the bioprinting of natural polymers, and limitations and prospects concerning future trends in human-scale tissue and organ fabrication are also presented. Full article

This in vitro study evaluated color change, mineral content, and morphology of enamel, pH and cytotoxicity of experimental bleaching agents containing 35% hydrogen peroxide (HP), titanium tetrafluoride (TiF${}_4$), Natrosol, and Chemygel. Sixty enamel/dentin blocks were randomly treated with (n = 10) HP; HP+Natrosol+Chemygel with different TiF${}_4$ concentrations: 0.05 g HPT0.5, 0.1 g HPT1, 0.2 g HPT2, 0.3 g HPT3, 0.4 g HPT4. Bleaching was performed in three sessions (3 × 15 min application). Color change (CIEL${}_{ab}$-$\Delta$$E_{ab}$, CIEDE2000-$\Delta$$E_{00}$, $\Delta$$W{I}_D$) and Knoop microhardness (KHN) were evaluated. Enamel morphology and composition were observed under scanning electron microscopy and energy-dispersive spectrometry (EDS), respectively. Cell viability of keratinocyte cells was evaluated using MTT assay. Data were analyzed by one-way ANOVA and LSD and Tukey tests, and two-way repeated measures ANOVA and Bonferroni ($\alpha$ = 5%). The pH and EDS were analyzed descriptively. Lightness-L* increased, and a* and b* parameters decreased, except for HPT3 and HPT4 (b*). HPT0.5, HPT1, and HPT2 exhibited $\Delta$$E_{ab}$ and $\Delta$$W{I}_D$ similar to HP. $\Delta$$E_{00}$ did not present statistical difference. HP, HPT0.5, and HPT1 promoted higher KHN. HPT0.5 exhibited no changes on enamel surface. Keratinocyte cells were viable when treated with T0.5, and weak viable for T1. Experimental agents exhibited acidic pH and Ti elements. HPT0.5 exhibited bleaching efficacy, maintained KHN without enamel alterations, and did not increase cytotoxicity. Full article

There is a great demand for biodegradable hydrogel, and cellulose enriched wastes materials are widely used to serve this purpose for various advance applications (e.g., biomedical and environmental). Sugarcane bagasse is cellulose-enriched agro-waste, abundantly grown in Bangladesh. This study aimed to treat sugarcane bagasse-based agro-waste using a sustainable and ecofriendly approach to produce hydrogel with super-swelling capacity for adsorption of copper, chromium, iron ions, methylene blue and drimaren red dyes. To increase the swelling property of hydrogels, copolymerization of hydrophilic monomers is an effective technique. Therefore, this study aimed to prepare hydrogel via free radical graft-copolymerization reaction among acrylamide, methyl methacrylate and treated bagasse in the presence of N,N-methylene-bis-acrylamide as a crosslinker and potassium persulphate as an initiator. To obtain maximum yield, reaction conditions were optimized. It was found that hydrogel obtained from chemically treated sugarcane bagasse showed maximum water absorption capacity of 228.0 g/g, whereas untreated bagassebased hydrogel could absorb ~50 g/g of water. Maximum adsorption capacity of 247.0 mg/g was found for copper ion. In addition, organic pollutant removal from industrial effluent also showed good performance, removing >90% of methylene blue and 62% of drimaren red dye, with shorter kinetics. The biodegradability study showed that after 90 days of exposure, the hydrogels degraded to about 43% of their own mass. Therefore, the produced hydrogel could be an alternative adsorbent to remove pollutants and also for other potential applications. Full article

Tongue cancer is one of the most common carcinomas of the head and neck region. The antitumor activities of statins, including lovastatin (LV), and the essential oil of eucalyptus (Eu oil), have been adequately reported. The aim of this study was to develop a nanoemulgel containing LV combined with Eu oil that could then be made into a nanoemulsion and assessed to determine its cytotoxicity against the cell line human chondrosarcoma-3 (HSC3) of carcinoma of the tongue. An I-optimal coordinate-exchange quadratic mixture design was adopted to optimize the investigated nanoemulsions. The droplet size and stability index of the developed formulations were measured to show characteristics of the nanoemulsions. The optimized LV loaded self-nanoemulsifying drug delivery system (LV-Eu-SNEDDS) was loaded into the gelling agent Carbopol 934 to develop the nanoemulgel and evaluated for its rheological properties. The cytotoxic efficiency of the optimized LV-Eu-SNEDDS loaded nanoemulgel was tested for cell viability, and the caspase-3 enzyme test was used against the HSC3 cell line of squamous carcinoma of the tongue. The optimized nanoemulsion had a droplet size of 85 nm and a stability index of 93%. The manufactured nanoemulgel loaded with the optimum LV-Eu-SNEDDS exhibited pseudoplastic flow with thixotropic behavior. The developed optimum LV-Eu-SNEDDS-loaded nanoemulgel had the best half-maximal inhibitory concentration (IC₅₀) and caspase-3 enzyme values of the formulations developed for this study, and these features improved the ability of the nanoemulsion-loaded gel to deliver the drug to the investigated target cells. In addition, the in vitro cell viability studies revealed the synergistic effect between LV and Eu oil in the treatment of tongue cancer. These findings illustrated that the LV-Eu-SNEDDS-loaded gel formulation could be beneficial in the local treatment of tongue cancer. Full article

Immediate dentin sealing (IDS) involves applying an adhesive system to dentin directly after tooth preparation, before impression. This was considered an alternate to delayed dentin sealing (DDS), a technique in which hybridization is performed following the provisional phase and just before the indirect restoration luting procedure. This study aimed to compare the bond strength of restorations to dentin of the IDS and the DDS techniques throughout a systematic review and meta-analysis. The following PICOS framework was used: population, indirect restorations; intervention, IDS; control, DDS; outcomes, bond strength; and study design, in vitro studies. PubMed (MedLine), The Cochrane Library, ISI Web of Science, Scielo, Scopus, and Embase were screened up to January 2022 by two reviewers (L.H. and R.B.). In vitro papers studying the bond strength to human dentin of the IDS technique compared to the DDS technique were considered. Meta-analyses were carried out by using a software program (Review Manager v5.4.1; The Cochrane Collaboration). Comparisons were made by considering the adhesive used for bonding (two-step etch-and-rinse, three step etch-and-rinse, one-step self-etch, two-step self-etch, and universal adhesives). A total of 3717 papers were retrieved in all databases. After full-text assessment, 22 potentially eligible studies were examined for qualitative analysis, leaving a total of 21 articles for the meta-analysis. For the immediate bond strength, regardless of the adhesive strategy used, the IDS technique improved the bond strength of restorations to the dentin (p < 0.001). Taking into account the subgroup analysis, it seems that the use of the IDS technique with a two-step etch-and-rinse or a one-step self-etch adhesive system does not represent any advantage over the DDS technique (p = 0.07, p = 0.15). On the other hand, for the aged bond strength, regardless of the adhesive strategy used, the IDS technique improved the bond strength of restorations to the dentin (p = 0.001). The subgroups analysis shows that this improvement is observed only when a three-step etch-and-rinse adhesive system (p < 0.001) or when a combination of an adhesive system plus a layer of flowable resin (p = 0.01) is used. The in vitro evidence suggests that the use of the IDS technique improves the bond strength of dentin to resin-based restorations regardless of the adhesive strategy used. The use of a three-step etch-and-rinse adhesive system or the combination of an adhesive system plus a layer of flowable resin seems to considerably enhance the bond strength in the long term. Full article

Active pharmaceutical ingredients (API) or drugs are normally not delivered as pure chemical substances (for the prevention or the treatment of any diseases). APIs are still generally administered in prepared formulations, also known as dosage forms. Topical administration is widely used to deliver therapeutic agents locally because it is convenient and cost-effective. Since earlier civilizations, several types of topical semi-solid dosage forms have been commonly used in healthcare society to treat various skin diseases. A topical drug delivery system is designed primarily to treat local diseases by applying therapeutic agents to surface level parts of the body such as the skin, eyes, nose, and vaginal cavity. Nowadays, novel semi-solids can be used safely in pediatrics, geriatrics, and pregnant women without the possibility of causing any allergy reactions. The novel hydrogels are being used in a wide range of applications. At first, numerous hydrogel research studies were carried out by simply adding various APIs in pure form or dissolved in various solvents to the prepared hydrogel base. However, numerous research articles on novel hydrogels have been published in the last five to ten years. It is expected that novel hydrogels will be capable of controlling the APIs release pattern. Novel hydrogels are made up of novel formulations such as nanoparticles, nanoemulsions, microemulsions, liposomes, self-nano emulsifying drug delivery systems, cubosomes, and so on. This review focus on some novel formulations incorporated in the hydrogel prepared with natural and synthetic polymers. Full article

Nanotechnology has the potential to generate advancements and innovations in formulations and delivery systems. This fast-developing technology has been widely exploited for diagnostic and therapeutic purposes. Today, cosmetic formulations incorporating nanotechnology are a relatively new yet very promising and highly researched area. The application of nanotechnology in cosmetics has been shown to overcome the drawbacks associated with traditional cosmetics and also to add more useful features to a formulation. Nanocosmetics and nanocosmeceuticals have been extensively explored for skin, hair, nails, lips, and teeth, and the inclusion of nanomaterials has been found to improve product efficacy and consumer satisfaction. This is leading to the replacement of many traditional cosmeceuticals with nanocosmeceuticals. However, nanotoxicological studies on nanocosmeceuticals have raised concerns in terms of health hazards due to their potential skin penetration, resulting in toxic effects. This review summarizes various nanotechnology-based approaches being utilized in the delivery of cosmetics as well as cosmeceutical products, along with relevant patents. It outlines their benefits, as well as potential health and environmental risks. Further, it highlights the regulatory status of cosmeceuticals and analyzes the different regulatory guidelines in India, Europe, and the USA and discusses the different guidelines and recommendations issued by various regulatory authorities. Finally, this article seeks to provide an overview of nanocosmetics and nanocosmeceuticals and their applications in cosmetic industries, which may help consumers and regulators to gain awareness about the benefits as well as the toxicity related to the continuous and long-term uses of these products, thus encouraging their judicious use. Full article

A viscoelastic rheometer was equipped with a sono-device and a water bath to enable measurement of storage moduli G′ and loss moduli G″ of biomass polysaccharide hydrogels such as Kanten agarose, κ-carrageenan, and konjac glucomannan under ultrasound (US) exposure. The action of low power of 43 kHz US on their hydrogels significantly decreased G′ of Kanten agarose and carrageenan after a few seconds of US exposure 0.1% strain. When US with 20 W output power was exposed under mechanical strain at 0.1%, lower values were obtained cyclically for 3 min US intervals. The values then reverted to the original moduli values when US was stopped in cases of Kanten agarose and carrageenan hydrogels. As G″ values were increased during US operation, the anhydro-L-galactose segments in their hydrogels were unable to relax the external US forces within the gel sufficiently, thereby leading to gel structure collapse at a higher strain percentage. These results suggest that US exposure induced deformational change in the hydrogel structure formed by hydrogen-bonded cross-links. However, US deformation was less in the case of deacetylated cross-linkage in konjac glucomannan hydrogel. Full article

Dextransucrases released by certain lactic acid bacteria form glucose polymers with predominantly α-1,6-linkages and may be exploited biotechnologically for the tailored production of polysaccharides with application potential. Despite releasing two closely related dextransucrases, previous studies showed that water kefir borne Liquorilactobacillus (L.) hordei TMW 1.1822 and L. nagelii TMW 1.1827 produce different amounts of polysaccharides with distinct particle sizes (molecular weight and radius of gyration) and molecular architectures. To investigate where these differences originate and thus to provide deeper insights into the functionally diverse nature of polysaccharide formation during water kefir fermentation, we constructed two variants of the L. nagelii dextransucrase—a full-length enzyme and a truncated variant, devoid of a C-terminal glucan-binding domain that reflects the domain architecture of the L. hordei dextransucrase—and applied them at various enzyme concentrations to form dextran over 24 h. The full-length enzyme exhibited a high activity, forming constant amounts of dextran until a four-fold dilution, whereas the truncated variant showed a gradual decrease in activity and dextran formation at an increasing dilution. The application of the full-length enzyme resulted in higher average particle sizes compared to the truncated variant. However, the dilution of the enzyme extracts also led to a slight increase in the average particle size in both enzymes. Neither the domain architecture nor the enzyme concentration had an impact on the structural architecture of the dextrans. The presented results thus suggest that the comparatively higher processivity of the L. nagelii dextransucrase is predominantly caused by the additional C-terminal glucan-binding domain, which is absent in the L. hordei dextransucrase. The average particle size may be influenced, to some extent, by the applied reaction conditions, whereas the structural architecture of the dextrans is most likely caused by differences in the amino acid sequence of the catalytic domain. Full article

The aim of this study was to investigate the potential of Linum usitatissimum mucilage, a natural polymer, in developing a sustained release hydrogel for orally delivered drugs that require frequent dosing. For this purpose, nicorandil (a model drug)-loaded hydrogels with various feed ratios of Linum usitatissimum mucilage, acrylamide (monomer) and methylene bis-acrylamide (crosslinker) were prepared. The newly synthesized hydrogel formulations were probed fundamentally with respect to swelling behaviour, solvent penetration, and the release of the drug from the hydrogels. Later, the selected formulations were further characterized by Fourier-transform infrared spectroscopy, thermal analysis, X-ray diffraction analysis, and scanning electron microscopy. The swelling coefficient demonstrated a linear relation with the polymer ratio; however, an inverse behaviour in the case of monomer and crosslinker was observed. The drug release studies, performed at pH 1.2 and 4.5 and considering the dynamic environment of GIT, demonstrated that all formulations followed the Korsmeyer–Peppas model, displaying a slow drug release via diffusion and polymer erosion. FTIR analysis confirmed the successful grafting of acrylamide on linseed mucilage. Furthermore, scanning electron microscopy revealed a clear surface morphology with folds and pinholes in the hydrogel. Therefore, based upon the in-vitro outcomes, it can be concluded that a promising sustained release hydrogel can be prepared from natural polymer, Linum usitatissimum mucilage, offering many-fold benefits over the conventional synthetic polymers for oral delivery of drugs. Full article

Localized intra-periodontal pocket drug delivery using an injectable in situ forming gel is an effective periodontitis treatment. The aqueous insoluble property of rosin is suitable for preparing a solvent exchange-induced in situ forming gel. This study aims to investigate the role of incorporating lime peel oil (LO) on the physicochemical properties of injectable in situ forming gels based on rosin loaded with 5% w/w doxycycline hyclate (DH) in dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP). Their gel formation, viscosity, injectability, mechanical properties, wettability, drug release, and antimicrobial activities were evaluated. The presence of LO slowed gel formation due to the loose precipitate formation of gel with a high LO content. The viscosity and injectability were slightly increased with higher LO content for the DH-loaded rosin-based in situ forming gel. The addition of 10% LO lowered gel hardness with higher adhesion. LO incorporation promoted a higher drug release pattern than the no oil-added formulation over 10 days and the gel formation rate related to burst drug release. The drug release kinetics followed the non-Fickian diffusion mechanism for oil-added formulations. LO exhibited high antimicrobial activity against Porphyromonas gingivalis and Staphylococcus aureus. The DH-loaded rosin in situ forming gel with an addition of LO (0, 2.5, 5, and 10% w/w) inhibited all tested microorganisms. Adding 10% LO to rosin-based in situ forming gel improved the antimicrobial activities, especially for the P. gingivalis and S. aureus. As a result, the study demonstrates the possibility of using an LO amount of less than 10% loading into a rosin-based in situ forming gel for efficient periodontitis treatment. Full article

Polysaccharides are attractive gelling agents in pharmacy due to their safety, biocompatibility, biodegradability, relatively easy way of preparation, and low price. Due to their variable physical-chemical properties, polysaccharides have potentialities to be used for designing new drug delivery systems for controlled drug release. In this comparative study, rheological and texture properties as well as the in vitro release of model drug ibuprofen (IBU) with 11 polysaccharide-based hydrogels were investigated. The in vitro release of IBU significantly differed between (i) neutral (hydroxy/alkylcelluloses), (ii) anionic (carboxyalkylcellulose and its sodium salt, tragacanth, carrageenan, xanthan gum), and (iii) cationic (chitosans) hydrogels due to different contribution of provided interactions and viscosity within the hydrogel groups. The drug release kinetics of each hydrogel system was evaluated for five kinetic models. Several combinations of cationic hydrogels with neutral or anionic ones were performed to illustrate possibilities of providing modified IBU release profiles. In this context, chitosan was presented as an effective modifier of diffusion profiles for negatively charged drugs formulated into combined polymeric systems, providing their prolonged release. The most appropriate hydrogel for the topical application (i.e., providing favorable rheological and texture properties along with the highest drug release) was selected from a studied series of polysaccharide-based hydrogels. Full article

Hydrogels are three-dimensional, cross-linked, and supramolecular networks that can absorb significant volumes of water. Hydrogels are one of the most promising biomaterials in the biological and biomedical fields, thanks to their hydrophilic properties, biocompatibility, and wide therapeutic potential. Owing to their nontoxic nature and safe use, they are widely accepted for various biomedical applications such as wound dressing, controlled drug delivery, bone regeneration, tissue engineering, biosensors, and artificial contact lenses. Herein, this review comprises different synthetic strategies for hydrogels and their chemical/physical characteristics, and various analytical, optical, and spectroscopic tools for their characterization are discussed. A range of synthetic approaches is also covered for the synthesis and design of hydrogels. It will also cover biomedical applications such as bone regeneration, tissue engineering, and drug delivery. This review addressed the fundamental, general, and applied features of hydrogels in order to facilitate undergraduates, graduates, biomedical students, and researchers in a variety of domains. Full article