Gels

Micro- and nanoemulsions are potential drug solubilizers and penetration enhancers through the high surfactant/co-surfactant content. This study aimed to evaluate the influence of minoxidil (MXD) solubilized in the microemulsions (MEs) on drug release by in vitro/ex vivo diffusion through the semi-permeable membrane Spectra/Por^® (Spectrum Laboratory, Gardena, CA, USA) and porcine ear skin. Moreover, a residual amount of drug in the skin after ex vivo diffusion was evaluated. The reference ME_R, lecithin-containing ME_L, and gelatin-containing ME_G were characterized in terms of their size, polydispersity index, density, viscosity, electrical conductivity and surface tension. Based on the in vitro diffusion, it can be argued that ME_L slowed down the drug release, while ME_R and ME_G have no significant effect compared to the sample, in which propylene glycol (PG) was used as a solubilizer. Determination of the residual drug amount in the skin after 6 h of the ex vivo permeation was demonstrated as the most valuable method to evaluate the effectiveness of the ME’s application. The results indicate that the most optimal MXD permeation enhancers in alginate gel were the natural surfactants containing MEs. MXD solubilization in ME_G and ME_L had caused more than 5% of the drug remaining in the skin, which is almost a 1.5-fold higher amount compared to the reference gel. Full article

Polyelectrolyte gels exhibit swelling behaviors that are dependent on the external environment. The swelling behaviors of highly charged polyelectrolyte gels can be well explained using the Flory–Rehner model combined with the Gibbs–Donnan effect and Manning’s counterion condensation effect (the FRGDM model). This study investigated the swelling properties of a series of model polyelectrolyte gels, namely tetra-polyacrylic acid-polyethylene glycol gels (Tetra-PAA-PEG gels), and determined the applicability of the FRGDM model. The swelling ratio (V_s/V₀) was well reproduced by the FRGDM model in the moderate swelling regime (V_s/V₀ < 10). However, in the high swelling regime (V_s/V₀ > 10), the FRGDM model is approx. 1.6 times larger than the experimental results. When we introduced the finite extensibility to the elastic free energy in the FRGDM model, the swelling behavior was successfully reproduced even in the high swelling regime. Our results reveal that finite extensibility is one of the factors determining the swelling equilibrium of highly charged polyelectrolyte gels. The modified FRGDM model reproduces well the swelling behavior of a wide range of polyelectrolyte gels. Full article

Carbohydrate based low molecular weight gelators have been an intense subject of study over the past decade. The self-assembling systems built from natural products have high significance as biocompatible materials and renewable resources. The versatile structures available from naturally existing monosaccharides have enriched the molecular libraries that can be used for the construction of gelators. The bottom-up strategy in designing low molecular weight gelators (LMWGs) for a variety of applications has been adopted by many researchers. Rational design, along with some serendipitous discoveries, has resulted in multiple classes of molecular gelators. This review covers the literature from 2017–2020 on monosaccharide based gelators, including common hexoses, pentoses, along with some disaccharides and their derivatives. The structure-based design and structure to gelation property relationships are reviewed first, followed by stimuli-responsive gelators. The last section focuses on the applications of the sugar based gelators, including their utilization in environmental remediation, ion sensing, catalysis, drug delivery and 3D-printing. We will also review the available LMWGs and their structure correlations to the desired properties for different applications. This review aims at elucidating the design principles and structural features that are pertinent to various applications and hope to provide certain guidelines for researchers that are working at the interface of chemistry, biochemistry, and materials science. Full article

Silk sericin (SS) produced by Bombyx mori is normally discarded as waste in manufacturing processes, which causes environmental pollution. Therefore, investigating the use of silk sericin has economic and environmental benefits. As a three-dimensional structure, the sericin-derived hydrogel was explored in different applications. However, many developed gelation procedures raise concerns regarding safety, cost, and duration of gelation time. In this work, “thiol-ene” click chemistry was used to quickly and controllably prepare an SS-derived hydrogel to resolve these early concerns. Then, berberine was loaded and used as a model for investigating the drug-release profiles of the prepared hydrogel. The experimental results revealed that this hydrogel is eligible for a long-term release of berberine. Throughout the antibacterial experiments, the released berberine maintained its antibacterial activity. Our work expands the application of SS in biomedical industries in an eco-friendly way. Furthermore, the discussed strategy could provide a reference for the subsequent development of SS-derived materials. Full article

Polymer networks were prepared by Steglich esterification using poly(sorbitol adipate) (PSA) and poly(sorbitol adipate)-graft-poly(ethylene glycol) mono methyl ether (PSA-g-mPEG₁₂) copolymer. Utilizing multi-hydroxyl functionalities of PSA, poly(ethylene glycol) (PEG) was first grafted onto a PSA backbone. Then the cross-linking of PSA or PSA-g-mPEG₁₂ was carried out with disuccinyl PEG of different molar masses (Suc-PEG_n-Suc). Polymers were characterized through nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). The degree of swelling of networks was investigated through water (D₂O) uptake studies, while for detailed examination of their structural dynamics, networks were studied using ¹³C magic angle spinning NMR (¹³C MAS NMR) spectroscopy, ¹H double quantum NMR (¹H DQ NMR) spectroscopy, and ¹H pulsed field gradient NMR (¹H PFG NMR) spectroscopy. These solid state NMR results revealed that the networks were composed of a two component structure, having different dipolar coupling constants. The diffusion of solvent molecules depended on the degree of swelling that was imparted to the network by the varying chain length of the PEG based cross-linking agent. Full article

A new kind of on-demand dissolution hydrogel is successfully synthesized by modification of chitosan using γ-selenobutyrolactone. The chitosan hydrogel with different selenium contents is formed by ring opening of γ-selenobutyrolactone with the amines of D-glucosamine units on the chitosan backbone. The structure of the hydrogel was confirmed by ¹H NMR, XRD and XPS. Its physical and biological properties were evaluated by rheology characterization, degradation tests and cytotoxicity test. The hydrogel showed excellent biocompatibility and good degradation properties under oxidation or reduction conditions. All the evidence demonstrated that this type of material has good prospects for dressing applications. Full article

Incremental changes in ionic composition, solvent quality, and temperature can lead to reversible and abrupt structural changes in many synthetic and biopolymer systems. In the biological milieu, this nonlinear response is believed to play an important functional role in various biological systems, including DNA condensation, cell secretion, water flow in xylem of plants, cell resting potential, and formation of membraneless organelles. While these systems are markedly different from one another, a physicochemical framework that treats them as polyelectrolytes, provides a means to interpret experimental results and make in silico predictions. This article summarizes experimental results made on ion-induced volume phase transition in a polyelectrolyte model gel (sodium polyacrylate) and observations on the above-mentioned biological systems indicating the existence of a steep response. Full article

We present a brief review of some important conceptual and practical aspects for the design and properties of molecular luminescent gelators and their gels. Topics considered include structural and dynamic aspects of the gels, including factors important to their ability to emit radiation from electronically excited states. Full article

Thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels have been attracting attention in a variety of functional materials, such as biomaterials, because they exhibit a volume phase transition phenomenon near physiological temperatures. However, the slow kinetics and small volume shrinkage of bulk PNIPAAm hydrogels upon heating greatly limit their practical application. Here, we report PNIPAAm hydrogels with phase-separated structures that exhibited ultrafast shrinking upon heating. The phase separation into a PNIPAAm-rich phase and a water-rich phase was formed through aqueous polymerization in the presence of NaClO₄ salt. Through structural analysis of the hydrogels, a topologically heterogeneous and porous structure was observed, which was highly dependent on the NaClO₄ concentration in the polymerization step. Compared to conventional PNIPAAm hydrogels, the phase-separated hydrogels exhibited much faster and larger shrinkage upon heating. Simultaneously, the hydrogels quickly released a large amount of water owing to the effective water channels inside them. The present method can be widely applied to general hydrogels, and it can address the numerous limitations of hydrogels in terms of operating programmability and deformation efficiency. Full article

Understanding how cancer cells migrate, and how this migration is affected by the mechanical and chemical composition of the extracellular matrix (ECM) is critical to investigate and possibly interfere with the metastatic process, which is responsible for most cancer-related deaths. In this article we review the state of the art about the use of hydrogel-based three-dimensional (3D) scaffolds as artificial platforms to model the mechanobiology of cancer cell migration. We start by briefly reviewing the concept and composition of the extracellular matrix (ECM) and the materials commonly used to recreate the cancerous ECM. Then we summarize the most relevant knowledge about the mechanobiology of cancer cell migration that has been obtained using 3D hydrogel scaffolds, and relate those discoveries to what has been observed in the clinical management of solid tumors. Finally, we review some recent methodological developments, specifically the use of novel bioprinting techniques and microfluidics to create realistic hydrogel-based models of the cancer ECM, and some of their applications in the context of the study of cancer cell migration. Full article

A convenient method for the preparation of polybasic ternary hybrid cryogels consisting of Halloysite nanotubes (HNTs) and tertiary amine functional groups by freezing-induced gelation is proposed. Ternary hybrid gels were produced via one-shot radical terpolymerization of 2-hydroxyethyl methacrylate (HEMA), 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS), and DEAEMA in the presence of HNTs. The equilibrium swelling in various swelling media and the mechanical properties of the produced ternary hybrid gels were analyzed to investigate their network structure and determine their final performance. The swelling ratio of HNT-free gels was significantly higher than the ternary hybrid gels composed of high amount of HNTs. The addition of HNTs to terpolymer network did not suppress pH- and temperature-sensitive behavior. While DEAEMA groups were effective for pH-sensitive swelling, it was determined that both HEMA and DEAEMA groups were effective in temperature-sensitive swelling. Ternary hybrid gels simultaneously demonstrated both negative and positive temperature-responsive swelling behavior. The swelling ratio changed considerably according to swelling temperature. Both DEAEMA and HEMA monomers in terpolymer structure were dominant in temperature-sensitive swelling. Mechanical tests in compression of both as-prepared and swollen-state demonstrated that strength and modulus of hybrid cryogels significantly increased with addition of HNTs without significant loss of mechanical strength. Ultimately, the results of the current system can benefit characterization with analysis tools for the application of innovative materials. Full article

The multicomponent preparations for mesotherapy are based on the principle that skin and hair aging can be prevented by supplying the fundamental substrates for correct cellular functioning, such as nucleotides, vitamins, amino acids, and biomolecules including hyaluronic acid (HA) that promote skin hydration and several biological activities. The study provides evidence for the application of HYDRO DELUXE BIO (Matex Lab S.p.A), a biocompatible hydrogel containing not cross-linked HA, for the treatment of the scalp’s skin by mesotherapy. Using an in vitro model of immortalized human keratinocytes, we studied markers involved in hair aging prevention and growth, such as inflammatory markers, angiogenesis, and oxidative damage. HYDRO DELUXE BIO showed high biocompatibility and the ability to significantly reduce the expression of the inflammation marker interleukin (IL)-8 in Tumor Necrosis Factor (TNF)-stimulated cells. Then, we evaluated angiogenesis, a pivotal event during hair growth, measuring the Vascular Endothelial Growth Factor (VEGF) expression that resulted to be significantly increased in treated cells, suggesting a pro-angiogenetic capability. A protective activity against the oxidative stress agent was showed, increasing the survival rate in treated cells. Concluding, HYDRO DELUXE BIO is suitable for treatment by mesotherapy of the scalp’s skin as it modulates the expression levels of markers involved in the biorevitalization of the hair follicle. Full article

The use of peptides to template inorganic nanoparticle formation has attracted great interest as a green route to advance structures with innovative physicochemical properties for a variety of applications that range from biomedicine and sensing, to catalysis. In particular, short-peptide gelators offer the advantage of providing dynamic supramolecular environments for the templating effect on the formation of inorganic nanoparticles directly in the resulting gels, and ideally without using further reductants or chemical reagents. This mini-review describes the recent progress in the field to outline future research directions towards dynamic functional materials that exploit the synergy between supramolecular chemistry, nanoscience, and the interface between organic and inorganic components for advanced performance. Full article

Hydrogels have played a significant role in many applications of regenerative medicine and tissue engineering due to their versatile properties in realizing design and functional requirements. However, as bioengineered solutions are translated towards clinical application, new hurdles and subsequent material requirements can arise. For example, in applications such as cell encapsulation, drug delivery, and biofabrication, in a clinical setting, hydrogels benefit from being comprised of natural extracellular matrix-based materials, but with defined, controllable, and modular properties. Advantages for these clinical applications include ultraviolet light-free and rapid polymerization crosslinking kinetics, and a cell-friendly crosslinking environment that supports cell encapsulation or in situ crosslinking in the presence of cells and tissue. Here we describe the synthesis and characterization of maleimide-modified hyaluronic acid (HA) and gelatin, which are crosslinked using a bifunctional thiolated polyethylene glycol (PEG) crosslinker. Synthesized products were evaluated by proton nuclear magnetic resonance (NMR), ultraviolet visibility spectrometry, size exclusion chromatography, and pH sensitivity, which confirmed successful HA and gelatin modification, molecular weights, and readiness for crosslinking. Gelation testing both by visual and NMR confirmed successful and rapid crosslinking, after which the hydrogels were characterized by rheology, swelling assays, protein release, and barrier function against dextran diffusion. Lastly, biocompatibility was assessed in the presence of human dermal fibroblasts and keratinocytes, showing continued proliferation with or without the hydrogel. These initial studies present a defined, and well-characterized extracellular matrix (ECM)-based hydrogel platform with versatile properties suitable for a variety of applications in regenerative medicine and tissue engineering. Full article

Olive oil has recognized health benefits but lacks structural resilience to act in a similar fashion as do the typically used triglycerides (TAGs) when applied in food manufacturing. Therefore, olive oil structuring is critical to widening its use as a healthier alternative in spreadable products. Foreseeing the development of an application for the food industry, three types of natural waxes were used as organogelators, generating olive oil organogels with distinct properties. Retail-simulated storage conditions were used to mimic real-life industrial and commercial use. Organogel systems were evaluated according to their oxidation stability and textural and rheological properties. Textural and rheological parameters increased in response to increasing gelator concentration, while oxidation values (below 1.5 meq O₂·kg⁻¹) remained within legal limits. Organogels displayed similar textural properties to those of commercially available spreadable products, while displaying a low critical gelation concentration. In short, it was shown that tailoring the physicochemical properties of organogels towards specific applications is possible. The produced organogels showed similar properties to the ones of commercially available spreadable products, revealing favourable oxidative profiles. Therefore, an industrial application can be easily foreseen, building on the natural characteristics of olive oil as a healthier alternative to current spreadable products. Full article

Plasma is regarded as a solution of precursor polymers specifically transformed to gel-forming polymers by a reaction with initiators. We developed a theory for the gel growth dynamics of plasma induced by contact with a source of gelators that are yielded by the initiation. In developing the theory, we combined the Ginzburg–Landau type dynamics with the gelator diffusion dynamics expressed by the moving boundary picture. The theory predicts the crossover of the rate-limiting process in the time course of the thickness of the gel layer X from the energy-limited process expressed by $X\sim t$ to the diffusion-limited process expressed by $X\sim \sqrt{t}$, where t is the time elapsed from when the plasma comes into contact with the source of gelators. A demonstration experiment was performed by placing a tissue factor coating plate as the initiator in plasma. Log–log plot of X vs. t showed a crossover as predicted by the theory, and the parameters characterizing plasma were determined. Full article

The aim of the current study was to fabricate naturally derived polymer based hydrogels for controlled release of diclofenac sodium (DS) for a long duration of time. In this research work, sodium alginate-co-poly(2-acrylamido-2-methyl propane sulphonic acid) (SA-co-poly(AMPS)) hydrogels were prepared by the free radical polymerization technique, where sodium alginate (SA) and 2-acrylamido-2-methyl propane sulphonic acid (AMPS) were used as the polymer and monomer while ammonium peroxodisulfate (APS) and N,N′-Methylene bisacrylamide (MBA) were used as the initiator and cross-linker, respectively. A swelling study was performed to determine the swelling index of developed hydrogels in both acidic (pH 1.2) and basic (pH 7.4) media and pH-independent swelling was observed due to the presence of AMPS. An in vitro release study was conducted to evaluate the percentage of drug released, and a high release of the drug was found at the higher pH of 7.4. Sol–gel analysis was performed to analyze the crosslinked and uncrosslinked part of the hydrogels, and results showed a rise in gel fraction as the composition of SA, AMPS and MBA increased while the sol fraction decreased and vice versa. This work demonstrated a potential for sustained delivery of diclofenac sodium by employing various concentration of SA, AMPS and MBA. Full article

Condyloma acuminata is an infectious disease caused by the human papilloma virus (HPV) and one of the most common sexually transmitted infections. It is manifested as warts that frequently cause pain, pruritus, burning, and occasional bleeding. Treatment (physical, chemical, or surgical) can result in erosion, scars, or ulcers, implying inflammatory processes causing pain. In this work, a biocompatible topical hydrogel containing 2% ketorolac tromethamine was developed to manage the painful inflammatory processes occurring upon the removal of anogenital condylomas. The hydrogel was physically, mechanically, and morphologically characterized: it showed adequate characteristics for a topical formulation. Up to 73% of ketorolac in the gel can be released following a one-phase exponential model. Upon application on human skin and vaginal mucosa, ketorolac can permeate through both of these and it can be retained within both tissues, particularly on vaginal mucosa. Another advantage is that no systemic side effects should be expected after application of the gel. The hydrogel showed itself to be well tolerated in vivo when applied on humans, and it did not cause any visible irritation. Finally, ketorolac hydrogel showed 53% anti-inflammatory activity, suggesting that it is a stable and suitable formulation for the treatment of inflammatory processes, such as those occurring upon chemical or surgical removal of anogenital warts. Full article