A concept of mixing energy, ME, has been developed and applied to blending of adhesive mixtures for inhalation in a high shear blender. Six different systems were investigated, four of which included a coating agent. For blends containing a coating agent, it is shown that the applied ME is key to the control of two important functional mechanisms i) coating of the carrier by the coating agent, and ii) the dispersibility of the active pharmaceutical ingredient (API). The mass of the carrier was identified to be the mass which is relevant to the forces acting during mixing. The dispersibility in terms of the fine particle fraction (FPF) can be expressed as the product of two exponentials which both are functions of ME. The first factor accounts for the initial increase in FPF, while the second accounts for the decrease observed at extensive mixing. For adhesive mixtures without a coating agent, a similar decrease in FPF is observed when high forces are applied during mixing. Mechanistic interpretation of the behavior is provided.The work was aimed at evaluating the efficiency of multifunctional magnesium aluminosilicate materials (MAS) as a novel glidant in solid dosage forms. MAS are known for their very low cohesive interactions and their utilization could avoid the disadvantages associated with conventional glidant usage. Flow properties of several mixtures comprising a model excipient (microcrystalline cellulose) and a glidant were characterized using a powder rheometer FT4. The mixtures were formulated to represent effects of glidant types, various levels of glidant loading, particle size and mixing time on flow properties of the model excipient. Pre-conditioning, shear testing, compressibility, flow energy measurements and an additional tapping test were carried out to monitor flow properties. Mixtures were analyzed employing scanning electron microscopy, using a detector of back-scattered electrons to identify a mechanism of MAS towards improving the mixture flow properties. All studied parameters were found to have substantial effects on mixture flow properties, but the effect of mixing time was much less important compared to mixtures based on traditional glidant.  https://www.selleckchem.com/products/bp-1-102.html  The mechanism of MAS glidant action was found to be different compared to that of traditional one, having less process sensitivity, so that MAS utilization as glidant could be advantageous for the formulation performance.In Colombia, the number of younger female surgeons is increasing along with a growing interest in thoracic and cardiac surgery. It is our duty to motivate young female surgeons in pursuing a career in chest surgery to answer the already growing deficit of cardio-thoracic surgeons.Cellular gene delivery via polycations has wide implications for the potential of gene therapy, but it has remained a challenge due to the plethora of pre- and post-uptake barriers that must be overcome to reach desired efficiency. Herein we report poly(hexamethylene biguanide) (PHMB) as a nano-vector for intracellular delivery of plasmid DNA (pDNA) and oligodeoxynucleotides (ODNs). PHMB and pDNA or ODNs self-assembled into complex nanoparticles at different pH values (7.4 and 12). Their size, charge, cellular uptake, and gene-expression efficiency are assessed and compared to PEI analogues. The systematic results show that the nanoparticles are effective in delivering plasmid DNA and ODNs to model cell lines in culture (HepG2, HEK293T, HeLa), with measurable changes in gene expression levels, comparable to and, in some conditions, even higher than PEI. The well-accepted safety profile of PHMB makes it a valuable candidate for consideration as an effective intracellular DNA vector for further study and potential clinical translation.B-cell linker protein (BLNK) is an adaptor protein that orchestrates signalling downstream of B-cell receptors. It has been reported to undergo proteasomal degradation upon binding to 14-3-3 proteins. Here, we report the first biophysical and structural study of this protein-protein interaction (PPI). Specifically, we investigated the binding of mono- and di- phosphorylated BLNK peptides to 14-3-3 using fluorescent polarization (FP) and isothermal titration calorimetry assays (ITC). Our results suggest that BLNK interacts with 14-3-3 according to the gatekeeper model, where HPK1 mediated phosphorylation of Thr152 (pT152) allows BLNK anchoring to 14-3-3, and an additional phosphorylation of Ser285 (pS285) by AKT, then further improves the affinity. Finally, we have also solved a crystal structure of the BLNKpT152 peptide bound to 14-3-3σ. These findings could serve as important tool for compound discovery programs aiming to modulate this interaction with 14-3-3.Macrophages are sentinels of the immune system, which are often hijacked by tumor cells to assist tumor growth and metastasis. Herein our results showed that low dose salinomycin (SAL) in the range of 10-50 nM could efficiently induce M1 macrophage polarization in a dose- and time- dependent manner in vitro, with 30 nM SAL being optimal to generate M1-type macrophages from RAW246.7 cells. In animal study, intratumorally injected SAL (50 µg/kg) increased proportion of CD86 cells (by 28.9%), and decreased CD206 cells (by 14.2%) in transplant 4T1 tumors, in comparison with PBS group. Thus it resulted in significant regression in tumor growth (20% tumor inhibition) and pulmonary metastasis (reduced the number of metastatic nodes by 58%) in SAL group, whereas lipopolysaccharide (LPS) and paclitaxel (PTX) groups showed comparable number of metastatic lesions and volume of tumor. LPS treatment could as well lead to inflammatory reactions in tumor with SAL group, but resulted in systemic inflammation (elevated levels of IL-1α, IL-1β and TNF-α in serum), and PTX (10 μg/kg) treatment increased both types of macrophages. For the first time, we employed salinomycin below the dose of direct antitumor activity could effectively prime M1 type macrophage stimulation and regress tumor growth and metastasis.The cutaneous drug delivery represents an attractive option for the management of skin diseases. However, the skin has a very complex morphological structure, although the skin barrier is disrupted in some of dermatological diseases. Therefore, to safely overcome the skin barrier and to deliver drugs across the skin efficiently is still remain as a challenge in the management of dermatological diseases. The nanocarrier mediated cutaneous delivery appears to offer a hope to provide targeting potential of the drugs into specific sites of the skin with minimizing side effects. This review highlights the human structure and diseased skin barrier, and possible therapeutic outcomes of nanocarrier based drug delivery in the treatment of skin diseases due to their skin transport and follicular targeting mechanisms, and summarizes recent studies in which polymer, lipid and surfactant based nanocarriers of drugs used in the skin diseases.