Chitosan/Pluronic F127 Thermosensitive Hydrogel as an Injectable Dexamethasone Delivery Carrier

Intra-articular administration of anti-inflammatory drugs is a strategy that allows localized action on damaged articular cartilage and reduces the side effects associated with systemic drug administration. The objective of this work is to prepare injectable thermosensitive hydrogels for the long-term application of dexamethasone. The hydrogels were prepared by mixing chitosan (CS) and Pluronic-F127 (PF) physically. In addition, tripolyphosphate (TPP) was used as a crosslinking agent. Chitosan added to the mix increased the gel time compared to the pluronic gel alone. The incorporation of TPP into the material modified the morphology of the hydrogels formed. Subsequently, MTS and Live/Dead® experiments were performed to investigate the toxicity of hydrogels against human chondrocytes. The in vitro releases of dexamethasone (DMT) from CS-PF and CS-PF-TPP gels had an initial burst and took more time than that from the PF hydrogel. In vivo studies showed that hydrogels retained the fluorescent compound longer in the joint than when administered in PBS alone. These results suggest that the CS-PF and CS-PF-TPP hydrogels loaded with DMT could be a promising drug delivery platform for the treatment of osteoarthritis.

Scrutinizing the Feasibility of Nonionic Surfactants to Form Isotropic Bicelles of Curcumin: a Potential Antiviral Candidate Against COVID-19

Investigating bicelles as an oral drug delivery system and exploiting their structural benefits can pave the way to formulate hydrophobic drugs and potentiate their activity. Herein, the ability of non-ionic surfactants (labrasol®, tween 80, cremophore EL and pluronic F127) to form curcumin loaded bicelles with phosphatidylcholine, utilizing a simple method, was investigated. Molecular docking was used to understand the mechanism of bicelles formation. The % transmittance and TEM exhibited bicelles formation with labrasol® and tween 80, while cremophor EL and pluronic F127 tended to form mixed micelles. The surfactant-based nanostructures significantly improved curcumin dissolution (99.2 ± 2.6% within 10 min in case of tween 80-based bicelles) compared to liposomes and curcumin suspension in non-sink conditions. The prepared formulations improved curcumin ex vivo permeation over liposomes and drug suspension. Further, the therapeutic antiviral activity of the formulated curcumin against SARS-CoV-2 was potentiated over drug suspension. Although both Labrasol® and tween 80 bicelles could form bicelles and enhance the oral delivery of curcumin when compared to liposomes and drug suspension, the mixed micelles formulations depicted superiority than bicelles formulations. Our findings provide promising formulations that can be utilized for further preclinical and clinical studies of curcumin as an antiviral therapy for COVID-19 patients.

Injectable and Temperature-Sensitive Titanium Carbide-Loaded Hydrogel System for Photothermal Therapy of Breast Cancer

Recently, organic–inorganic hybrid materials have gained much attention as effective photothermal agents for cancer treatment. In this study, Pluronic F127 hydrogel-coated titanium carbide (Ti3C2) nanoparticles were utilized as an injectable photothermal agent. The advantages of these nanoparticles are their green synthesis and excellent photothermal efficiency. In this system, lasers were mainly used to irradiate Ti3C2 nanoparticles to produce a constant high temperature, which damaged cancer cells. The nanoparticles were found to be stable during storage at low temperatures for at least 2 weeks. The Ti3C2 nanoparticles exhibited a shuttle-shaped structure, and the hydrogels presented a loosely meshed structure. In addition, Ti3C2 nanoparticles did not affect the reversible temperature sensitivity of the gel, and the hydrogel did not affect the photothermal properties of Ti3C2 nanoparticles. The in vitro and in vivo results show that this hydrogel system can effectively inhibit tumor growth upon exposure to near-infrared irradiation with excellent biocompatibility and biosafety. The photothermal agent-embedded hydrogel is a promising photothermal therapeutic strategy for cancer treatment by enhancing the retention in vivo and elevating the local temperature in tumors.

Effect of Functional Group on the Catalytic Activity of Lipase B from Candida antarctica Immobilized in a Silica-Reinforced Pluronic F127/α-Cyclodextrin Hydrogel

Surface modification plays a key role in the fabrication of highly active and stable enzymatic nanoreactors. In this study, we report for the first time the effect of various functional groups (epoxy, amine, trimethyl, and hexadecyl) on the catalytic performance of lipase B from Candida antarctica (CALB) incorporated within a monolithic supramolecular hydrogel with multiscale pore architecture. The supramolecular hydrogel formed by host-guest interactions between α-cyclodextrin (α-CD) and Pluronic F127 was first silicified to provide a hierarchically porous material whose surface was further modified with different organosilanes permitting both covalent anchoring and interfacial activation of CALB. The catalytic activity of nanoreactors was evaluated in the liquid phase cascade oxidation of 2,5-diformylfuran (DFF) to 2,5-furandicarboxylic acid (FDCA) under mild conditions. Results showed that high FDCA yields and high efficiency conversion of DFF could be correlated with the ability of epoxy and amine moieties to keep CALB attached to the carrier, while the trimethyl and hexadecyl groups could provide a suitable hydrophobic-hydrophilic interface for the interfacial activation of lipase. Cationic cross-linked β-CD was also evaluated as an enzyme-stabilizing agent and was found to provide beneficial effects in the operational stability of the biocatalyst. These supramolecular silicified hydrogel monoliths with hierarchical porosity may be used as promising nanoreactors to provide easier enzyme recovery in other biocatalytic continuous flow processes.

Experimental Studies on the Removal of Aluminium Ions from Synthetic Aqueous Solution by Hydroxyapatites

In this work we have presented the results obtained in the adsorption behavior of hydroxyapatite with different treatment towards aluminium ions from synthetic wastewaters. Experiments were performed in batch technique at different pH values, temperatures, sorbent dosage, contact time and initial aluminium concentration. The thermodynamic studies on the adsorption process of aluminium onto hydroxyapatite indicated that the process is spontaneous and endothermic. The Langmuir, Freundlich, Flory-Huggins, Dubinin-Radushkevich and Temkin equilibrium models were applied to the description of experimental data. The adsorption of aluminium follows the Langmuir adsorption isotherm. The kinetics of adsorption was evaluated using the pseudo-first order, pseudo-second order and intraparticle diffusion kinetic models. The rate of aluminium adsorption was successfully described by a pseudo-second-order kinetic model. The obtained results indicated that hydroxyapatite treated with Pluronic P123 surfactant has a higher sorption capacity toward aluminium ions (117.65 mg g−1) than hydroxyapatite treated with Pluronic F127 surfactant (109.89 mg g−1) while untreated hydroxyapatite exhibited the lowest one (104.17 mg g−1).

Nano-Sized Extracellular Matrix Particles Lead to Therapeutic Improvement for Cutaneous Wound and Hindlimb Ischemia

Cell-derived matrix (CDM) has proven its therapeutic potential and been utilized as a promising resource in tissue regeneration. In this study, we prepared a human fibroblast-derived matrix (FDM) by decellularization of in vitro cultured cells and transformed the FDM into a nano-sized suspended formulation (sFDM) using ultrasonication. The sFDM was then homogeneously mixed with Pluronic F127 and hyaluronic acid (HA), to effectively administer sFDM into target sites. Both sFDM and sFDM containing hydrogel (PH/sFDM) were characterized via immunofluorescence, sol–gel transition, rheological analysis, and biochemical factors array. We found that PH/sFDM hydrogel has biocompatible, mechanically stable, injectable properties and can be easily administered into the external and internal target regions. sFDM itself holds diverse bioactive molecules. Interestingly, sFDM-containing serum-free media helped maintain the metabolic activity of endothelial cells significantly better than those in serum-free condition. PH/sFDM also promoted vascular endothelial growth factor (VEGF) secretion from monocytes in vitro. Moreover, when we evaluated therapeutic effects of PH/sFDM via the murine full-thickness skin wound model, regenerative potential of PH/sFDM was supported by epidermal thickness, significantly more neovessel formation, and enhanced mature collagen deposition. The hindlimb ischemia model also found some therapeutic improvements, as assessed by accelerated blood reperfusion and substantially diminished necrosis and fibrosis in the gastrocnemius and tibialis muscles. Together, based on sFDM holding a strong therapeutic potential, our engineered hydrogel (PH/sFDM) should be a promising candidate in tissue engineering and regenerative medicine.

A thermoreversible antibacterial zeolite-based nanoparticles loaded hydrogel promotes diabetic wound healing via detrimental factor neutralization and ROS scavenging

Background As recovery time of diabetic wound injury is prolonged by the production of detrimental factors, including reactive oxygen species (ROS) and inflammatory cytokines, attenuating the oxidative stress and inflammatory reactions in the microenvironment of the diabetic wound site would be significant. Experimental design In our study, we prepared thermoreversible, antibacterial zeolite-based nanoparticles loaded hydrogel to promote diabetic wound healing via the neutralization of detrimental factors such as inflammatory cytokines and ROS. Results The cerium (Ce)-doped biotype Linde type A (LTA) zeolite nanoparticles synergistically eliminated mitochondrial ROS and neutralized free inflammatory factors, thus remodeling the anti-inflammatory microenvironment of the wound and enhancing angiogenesis. Moreover, the thermoreversible hydrogel composed of Pluronic F127 and chitosan demonstrated strong haemostatic and bactericidal behavior. Conclusions In conclusion, the obtained thermoreversible, antibacterial, zeolite-based nanoparticles loaded hydrogels represent a multi-targeted combination therapy for diabetic wound healing. Graphical Abstract