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Edaravone (Edv) can inhibit tissue damage, cause cerebral edema, and delay neuronal death caused by acute cerebral infarction. CUDC-907 Exosomes are considered as cargo carriers for intercellular communication and serve as important regulators in many pathological processes. Here, we developed macrophage-derived exosomes (Exo) containing Edv (Exo + Edv) to improve the bioavailability of Edv and enhance the neuroprotective effects in a rat model of permanent middle cerebral artery occlusion (PMCAO). The results showed that Exo + Edv significantly improved the bioavailability of Edv and prolonged half-life (t1/2). At the same time, Exo + Edv made Edv more easily reach the ischemic side of rats with PMCAO and was localized with neuronal cells and microglia, thus reducing the death of neuronal cells and promoting the polarization of microglia from M1 to M2. Taken together, Exo + Edv may become a potential clinical treatment option for PMCAO.Protein inactivation either during the production process or along the gastrointestinal tract is the major problem associated with the development of oral delivery systems for biological drugs. This work presents an evaluation of the structural integrity and the biological activity of a model protein, catalase, after its encapsulation in glyceryl trimyristate-based solid lipid microparticles (SLMs) obtained by the spray congealing technology. Circular dichroism and fluorescence spectroscopies were used to assess the integrity of catalase released from SLMs. The results confirmed that no conformational change occurred during the production process and both the secondary and tertiary structures were retained. Catalase is highly sensitive to temperature and undergoes denaturation above 60 °C; nevertheless, spray congealing allowed the retention of most biological activity due to the loading of the drug at the solid state, markedly reducing the risk of denaturation. Catalase activity after exposure to simulated gastric conditions (considering both acidic pH and the presence of gastric digestive hydrolases) ranged from 35 to 95% depending on the carrier increasing of both the fatty acid chain length and the degree of substitution of the glyceride enhanced residual enzyme activity. SLMs allowed the protein release in a simulated intestinal environment and were not cytotoxic against HT29 cells. In conclusion, the encapsulation of proteins into SLMs by spray congealing might be a promising strategy for the formulation of nontoxic and inexpensive oral biotherapeutic products.The reversibility of solid-state hydrogen-deuterium exchange (ssHDX) and the effects of prehydration on the rate and extent of deuterium incorporation were evaluated using poly-d,l-alanine (PDLA) peptides colyophilized with various excipients. In prehydration studies, samples were equilibrated at a controlled relative humidity (6% or 11% RH) for 12 h and then transferred to corresponding D2O humidity conditions (6% or 11% RD) for deuterium labeling. In amorphous samples, the rate and extent of deuterium incorporation were similar in prehydrated samples and controls not subjected to prehydration. In reversibility studies, PDLA samples were maximally deuterated in controlled D2O humidity conditions (6% or 11% RD) and then transferred to corresponding H2O relative humidity (0%, 6%, 11%, or 43% RH). Hysteresis in deuterium removal was observed when compared with the deuterium incorporation kinetics for all formulations and conditions, confirming that the reaction is reversible in the solid state and that the forward and reverse processes differ. The extent of deuterium loss reached a plateau that depended on the delabeling relative humidity. Reverse reaction rate constants were quantified using a first-order kinetic model, a limiting case of the reversible first-order model applicable under sink conditions. For other conditions, plateau (steady-state) deuteration levels were related to forward and reverse rate constants in a reversible first-order kinetic model. The results support a mechanistic interpretation of ssHDX kinetics as a reversible first-order process, in which the forward (deuteration) rate depends on the activity of the deuterium donor.We studied the rotational and translational diffusion of a single gold nanorod linked to a supported lipid bilayer with ultrahigh temporal resolution of two microseconds. By using a home-built polarization-sensitive dark-field microscope, we recorded particle trajectories with lateral precision of 3 nm and rotational precision of 4°. The large number of trajectory points in our measurements allows us to characterize the statistics of rotational diffusion with unprecedented detail. Our data show apparent signatures of anomalous diffusion such as sublinear scaling of the mean-squared angular displacement and negative values of angular correlation function at small lag times. However, a careful analysis reveals that these effects stem from the residual noise contributions and confirms normal diffusion. Our experimental approach and observations can be extended to investigate diffusive processes of anisotropic nanoparticles in other fundamental systems such as cellular membranes or other two-dimensional fluids.Spin-dependent transport at heavy metal/magnetic insulator interfaces is at the origin of many phenomena at the forefront of spintronics research. A proper quantification of the different interfacial spin conductances is crucial for many applications. Here, we report the first measurement of the spin Hall magnetoresistance (SMR) of Pt on a purely ferromagnetic insulator (EuS). We perform SMR measurements in a wide range of temperatures and fit the results by using a microscopic model. From this fitting procedure, we obtain the temperature dependence of the spin conductances (Gs, Gr, and Gi), disentangling the contribution of field-like torque (Gi), damping-like torque (Gr), and spin-flip scattering (Gs). An interfacial exchange field of the order of 1 meV acting upon the conduction electrons of Pt can be estimated from Gi, which is at least three times larger than Gr below the Curie temperature. Our work provides an easy method to quantify this interfacial spin-splitting field, which plays a key role in emerging fields such as superconducting spintronics and caloritronics as well as topological quantum computation.
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