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Development and Characterization of Thermosensitive and Bioadhesive Ophthalmic Formulations Containing Flurbiprofen Solid Dispersions

In this study, we aimed to develop thermosensitive and bioadhesive in situ gelling systems containing solid dispersions of flurbiprofen (FB-SDs) using poloxamer 407 (P407) and 188 (P188) for ophthalmic delivery. FB-SDs were prepared with the melt method using P407, characterized by solubility, stability, SEM, DSC, TGA, and XRD analyses. Various formulations of poloxamer mixtures and FB-SDs were prepared using the cold method and P407/P188 (15/26.5%), which gels between 32 and 35 °C, was selected to develop an ophthalmic in situ gelling system. Bioadhesive polymers Carbopol 934P (CP) or carboxymethyl cellulose (CMC) were added in three concentrations (0.2, 0.4, and 0.6% (w/w)). Gelation temperature and time, mechanical properties, flow properties, and viscosity values were determined. The in vitro release rate, release kinetics, and the release mechanism of flurbiprofen (FB) from the ophthalmic formulations were analyzed. The results showed that FB-SDs’ solubility in water increased 332-fold compared with FB. The oscillation study results indicated that increasing bioadhesive polymer concentrations decreased gelation temperature and time, and formulations containing CP gel at lower temperatures and in a shorter time. All formulations except F3 and F4 showed Newtonion flow under non-physiological conditions, while all formulations exhibited non-Newtonion pseudoplastic flow under physiological conditions. Viscosity values increased with an increase in bioadhesive polymer concertation at physiological conditions. Texture profile analysis (TPA) showed that CP-containing formulations had higher hardness, compressibility, and adhesiveness, and the gel structure of formulation F4, containing 0.6% CP, exhibited the greatest hardness, compressibility, and adhesiveness. In vitro drug release studies indicated that CP and CMC had no effect below 0.6% concentration. Kinetic evaluation favored first-order and Hixson–Crowell kinetic models. Release mechanism analysis showed that the n values of the formulations were greater than 1 except for formulation F5, suggesting that FB might be released from the ophthalmic formulations by super case II type diffusion. When all the results of this study are evaluated, the in situ gelling formulations prepared with FB-SDs that contained P407/P188 (15/26.5%) and 0.2% CP or 0.2% CMC or 0.4 CMC% (F2, F5, and F6, respectively) could be promising formulations to prolong precorneal residence time and improve ocular bioavailability of FB.

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Coated Microneedle System for Delivery of Clotrimazole in Deep-Skin Mycoses

Mycoses of the skin are infectious diseases caused by fungal microorganisms that are generally treated with topical agents. However, such therapy is often ineffective and has to be supported by oral use of active substances, which, in turn, can cause many side effects. A good alternative for the treatment of deep-skin mycoses seems to be microneedles (MNs). The aim of this research was to fabricate and evaluate the properties of innovative MNs coated with a hydrogel as potential carriers for clotrimazole (CLO) in the treatment of deep fungal skin infections. A 3D printing technique using a photo-curable resin was employed to produce MNs, which were coated with hydrogels using a dip-coating method. Hydrogels were prepared with carbopol EZ-3 Polymer (Lubrizol) in addition to glycerol and triisopropanolamine. Clotrimazole was introduced into the gel as the solution in ethanol or was suspended. In the first step of the investigation, a texture analysis of hydrogels was prepared with a texture analyzer, and the drug release studies were conducted with the use of automatic Franz diffusion cells. Next, the release profiles of CLO for coated MNs were checked. The last part of the investigation was the evaluation of the antifungal activity of the prepared systems, and the inhibition of the growth of Candida albicans was checked with the diffusion and suspended-plate methods. The texture profile analysis (TPA) for the tested hydrogels showed that the addition of ethanol significantly affects the following studied parameters: hardness, adhesiveness and gumminess, causing a decrease in their values. On the other hand, for the gels with suspended CLO, better spreadability was seen compared to gels with dissolved CLO. The presence of the active substance did not significantly affect the values of the tested parameters. In the dissolution study, the results showed that higher amounts of CLO were released for MNs coated with a hydrogel containing dissolved CLO. Also, microbiological tests proved its efficacy against fungal cultures. Qualitative tests carried out using the diffusion method showed that circular zones of inhibition of fungal growth on the plate were obtained, confirming the hypothesis of effectiveness. The suspension-plate technique confirmed the inhibitory effect of applied CLO on the growth of Candida albicans. From the analysis of the data, the MNs coated with CLO dissolved in hydrogel showed better antifungal activity. All received results seem to be helpful in developing further studies for MNs as carriers of antifungal substances.

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Hydrophobic Silk Fibroin–Agarose Composite Aerogel Fibers with Elasticity for Thermal Insulation Applications

Aerogel fibers, characterized by their ultra-low density and ultra-low thermal conductivity, are an ideal candidate for personal thermal management as they hold the potential to effectively reduce the energy consumption of room heating and significantly contribute to energy conservation. However, most aerogel fibers have weak mechanical properties or require complex manufacturing processes. In this study, simple continuous silk fibroin–agarose composite aerogel fibers (SCAFs) were prepared by mixing agarose with silk fibroin through wet spinning and rapid gelation, followed by solvent replacement and supercritical carbon dioxide treatment. Among them, the rapid gelation of the SCAFs was achieved using agarose physical methods with heat-reversible gel properties, simplifying the preparation process. Hydrophobic silk fibroin–agarose composite aerogel fibers (HSCAFs) were prepared using a simple chemical vapor deposition (CVD) method. After CVD, the HSCAFs’ gel skeletons were uniformly coated with a silica layer containing methyl groups, endowing them with outstanding radial elasticity. Moreover, the HSCAFs exhibited low density (≤0.153 g/cm3), a large specific surface area (≥254.0 m2/g), high porosity (91.1–94.7%), and excellent hydrophobicity (a water contact angle of 136.8°). More importantly, they showed excellent thermal insulation performance in low-temperature (−60 °C) or high-temperature (140 °C) environments. The designed HSCAFs may provide a new approach for the preparation of high-performance aerogel fibers for personal thermal management.

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Time Dependence of Gel Formation in Lyotropic Nematic Liquid Crystals: From Hours to Weeks

The combination of lyotropic liquid crystals (LLCs) and low-molecular-weight gelators (LMWGs) for the formation of lyotropic liquid crystal gels (LLC gels) leads to a versatile and complex material combining properties of both parent systems. We gelled the calamitic nematic NC phases of a binary and ternary system using the LMWG 3,5-bis-(5-hexylcarbamoyl-pentoxy)-benzoic acid hexyl ester (BHPB-6). This binary system consists of the surfactant N,N-dimethyl-N-ethyl-1-hexadecylammonium bromide (CDEAB) and water, whereas the ternary system consists of the surfactant N,N,N-trimethyl-N-tetradecylammonium bromide (C14TAB), the cosurfactant n-decanol, and water. Though containing similar surfactants, the gelled NC phases of the binary and ternary systems show differences in their visual and gel properties. The gelled NC phase of the binary system remains clear for several days after preparation, whereas the gelled NC phase of the ternary system turns turbid within 24 h. We investigated the time evolution of the gel strength with oscillation rheology measurements (a) within the first 24 h and (b) up to two weeks after gel formation. The shape of the fibers was investigated over different time scales with freeze fracture electron microscopy (FFEM). We demonstrate that despite their similarities, the two LLC gels also have distinct differences.

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A High-Stretching, Rapid-Self-Healing, and Printable Composite Hydrogel Based on Poly(Vinyl Alcohol), Nanocellulose, and Sodium Alginate

Hydrogels with excellent flexibility, conductivity, and controllable mechanical properties are the current research hotspots in the field of biomaterial sensors. However, it is difficult for hydrogel sensors to regain their original function after being damaged, which limits their practical applications. Herein, a composite hydrogel (named SPBC) of poly(vinyl alcohol) (PVA)/sodium alginate (SA)/cellulose nanofibers (CNFs)/sodium borate tetrahydrate was synthesized, which has good self-healing, electrical conductivity, and excellent mechanical properties. The SPBC0.3 hydrogel demonstrates rapid self-healing (<30 s) and achieves mechanical properties of 33.92 kPa. Additionally, it exhibits high tensile strain performance (4000%). The abundant internal ions and functional groups of SPBC hydrogels provide support for the good electrical conductivity (0.62 S/cm) and electrical response properties. In addition, the SPBC hydrogel can be attached to surfaces such as fingers and wrists to monitor human movements in real time, and its good rheological property supports three-dimensional (3D) printing molding methods. In summary, this study successfully prepared a self-healing, conductive, printable, and mechanically superior SPBC hydrogel. Its suitability for 3D-printing personalized fabrication and outstanding sensor properties makes it a useful reference for hydrogels in wearable devices and human motion monitoring.

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Heavy Metal Removal from Wastewater Using Poly(Gamma-Glutamic Acid)-Based Hydrogel

The removal of toxic heavy metal ions from wastewater is of great significance in the protection of the environment and human health. Poly(gamma-glutamic acid) (PGA) is a non-toxic, biodegradable, and highly water-soluble polymer possessing carboxyl and imino functional groups. Herein, water-insoluble PGA-based hydrogels were prepared, characterized, and investigated as heavy metal adsorbents. The prepared hydrogels were recyclable and exhibited good adsorption effects on heavy metal ions including Cu2+, Cr6+, and Zn2+. The effects of adsorption parameters including temperature, solution pH, initial concentration of metal ions, and contact time on the adsorption capacity of the hydrogel for Cu2+ were investigated. The adsorption was a spontaneous and exothermic process. The process followed the pseudo-first-order kinetic model and Langmuir isotherm model, implying a physical and monolayer adsorption. The adsorption mechanisms investigation exhibited that Cu2+ adsorbed on the hydrogel via electrostatic interactions with anionic carboxylate groups of PGA in addition to the coordination interactions with the –NH groups. Importantly, the PGA hydrogel exhibited good reusability and the adsorption capability for Cu2+ remained high after five consecutive cycles. The properties of PGA hydrogel make it a potential candidate material for heavy metal ion removal in wastewater treatment.

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