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The DSC data at relatively small concentrations of ligands are in good agreement with the calculation results. The deviations from the model predictions at high ligand concentrations in the cases of naproxen and ibuprofen indicate that albumin is able to bind several additional molecules of these drugs with its low-affinity sites. The fit was improved by using a sequential binding model with two binding constants K1 = 1.0 × 107 and K2 = 1.0 × 104 for naproxen and a cooperative binding model for ibuprofen. The stoichiometry of drug-albumin complexes fully saturated with drug ligand was calculated from the dependence of the denaturation temperature on the drug concentration. In the case of isoniazid, DSC thermograms indicated very weak binding to albumin. Amorphous ternary solid dispersions of poorly water-soluble Naringenin (NRG) in Poloxamer 188 (POX) and Neusilin US2 (NSL) were prepared in a Hot- Melt Extruder (HME) using the principle of Low-Temperature Solubilization (LTS). Before HME, the NRG-POX solid-state interaction was investigated using Flory Huggins (F-H) theory. Construction of the composition-phase diagram showed Gibbs free energy to be negative close to the melting temperature of NRG, indicating a miscible system. The temperature-composition phase diagram provided insights on the phase behavior of the active-polymer solid dispersion system. The interactions and phase behavior predicted within the framework of the F-H theory were further investigated using Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), Hot Stage Microscopy (HSM) and Fourier-transform infrared spectroscopy (FT-IR). Based on the findings, amorphous solid dispersions of NRG were prepared via HME, which demonstrated a significant increase in the dissolution rate (p ≤ 0.05). The enhancement of the dissolution rate is due to conversion from crystalline to amorphous form, as confirmed by DSC and XRD. The amorphous NRG prepared in the current study exhibited a release of 77% at the end of 2 h, which is an increment of 250% from that of pure crystals. Aripiprazole (ARP) is an antipsychotic drug approved for the treatment of schizophrenia. It is poorly water-soluble and undergoes extensive hepatic metabolism and P-gp efflux, which lead to poor bioavailability and increased dose-related side effects. This study focuses on the preparation of mixed micelles (MM) to enhance the aqueous solubility, oral bioavailability, and blood-brain barrier permeation of ARP. For this purpose, Soluplus and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were selected for micelle preparation (ARP-MM). Micelles with borneol as penetration enhancer were also considered (ARP-B-MM). The optimized formulations have sizes of ca 50 nm, defined in distilled water, narrow size distribution (polydispersity index ≤0.1), and high encapsulation efficiency (greater than98%). Both formulations can be freeze-dried without losing their chemical-physical characteristics and are stable during storage for three months. The mixed micelles resulted stable in enzyme free-simulated gastric filability of ARP, as demonstrated by the increase of the pharmacokinetic parameters, such as Cmax, AUC0-24h, and t1/2. Mechanical ventilation may contribute to the impairment of the pulmonary surfactant system, which is one of the mechanisms leading to the progression of acute lung injury. To investigate the potential protective effects of pulmonary surfactant in a rat model of ventilator-induced lung injury, the surfactant powder was aerosolized using an in-house made device designed to deliver the aerosolized powder to the inspiratory line of a rodent ventilator circuit. Rats were randomized to (i) administration of aerosolized recombinant surfactant protein C based pulmonary surfactant, (ii) intratracheally instillation of the same surfactant re-constituted in saline, and (iii) no treatment. Animals were monitored during 2 h of high-tidal volume mechanical ventilation, after which rats were sacrificed, and further analysis of lung mechanics and surfactant function were completed. Blood gas measurements during ventilation showed extended maintenance of oxygen levels above 400 mmHg in aerosol treated animals over non-treated and instilled groups, while total protein analysis showed reduced levels in the aerosol compared to non-treated groups. Dynamic captive bubble surface tension measurements showed the activity of surfactant recovered from aerosol treated animals is maintained below 1 mN/m. The prophylactic treatment of aerosolized surfactant powder reduced the severity of lung injury in this model. learn more Global rise in obesity-associated type 2 diabetes mellitus (T2DM) has led to a major healthcare crisis. Development of efficient treatments to treat the underlying chronic inflammation in obesity-associated T2DM, is an unmet medical need. To this end, we have developed a plasmid adiponectin (pADN) based nanomedicine for the treatment of insulin resistance in type 2 diabetes mellitus. Adiponectin is a potent anti-inflammatory/anti-diabetic adipokine, which is downregulated in obesity. In this study, nanomicelles comprising chitosan conjugated to oleic acid and adipose homing peptide (AHP) were developed to deliver pADN to adipocytes. Cationic chitosan-oleic-AHP micelles were 112 nm in size, encapsulated 93% of pADN and protected gene cargo from DNase I mediated enzymatic degradation. In vitro, the nanomicellar formulation significantly increased adiponectin production compared to free plasmid as well as standard transfecting agent FuGENE®HD. Single dose subcutaneous administration of pADN-chitosan-oleic-AHP to obese-diabetic rats, resulted in improved insulin sensitivity for up to 6 weeks, which matched the glucose disposal ability of healthy rats. Serum adiponectin level in pADN-chitosan-oleic-AHP treated rats was comparable to healthy rats for up to 3 weeks post treatment. Overall, the results indicate that pADN-chitosan-oleic-AHP based therapy is a promising treatment approach for obesity-associated T2DM. Published by Elsevier B.V.The COVID-19 pandemic has led to high levels of psychological distress in the general public, including symptoms of anxiety and depression. Such distress is associated with alterations in immune function, including an elevated risk of viral respiratory tract infections. In this light, the possible effects of Ayurveda, a traditional system of medicine promoted by the Indian government as an "immune booster", are examined from the point of view of psychoneuroimmune mechanisms as well as the "meaning response" described by Moerman. It was found that many of the measures advocated in their guidelines could positively influence immunity either by direct effects on symptoms of depression or anxiety, or through their symbolic significance. Therefore, it is possible that such traditional practices could be beneficial both in terms of psychological quality of life, and in terms of moderating the risk of infection.

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