Probing the Complex Loading-Dependent Structural Changes in Ultrahigh Drug-Loaded Polymer Micelles by Small-Angle Neutron Scattering

Drug-loaded polymer micelles or nanoparticles are being continuously explored in the fields of drug delivery and nanomedicine. Commonly, a simple core-shell structure is assumed, in which the core incorporates the drug and the corona provides steric shielding, colloidal stability, and prevents protein adsorption. Recently, the interactions of the dissolved drug with the micellar corona have received increasing attention. Here, using small-angle neutron scattering, we provide an in-depth study of the differences in polymer micelle morphology of a small selection of structurally closely related polymer micelles at different loadings with the model compound curcumin. This work supports a previous study using solid-state nuclear magnetic resonance spectroscopy and we confirm that the drug resides predominantly in the core of the micelle at low drug loading. As the drug loading increases, neutron scattering data suggests that an inner shell is formed, which we interpret as the corona also starting to incorporate the drug, whereas the outer shell mainly contains water and the polymer. The presented data clearly shows that a better understanding of the inner morphology and the impact of the hydrophilic block can be important parameters for improved drug loading in polymer micelles as well as provide insights into the structure-property relationship.Peer reviewe

Effects of health promotion program on maternal attachment, parenting self-efficacy, infant development: a randomised controlled trial

This study was designed to test the efficacy of the health promotion program used on maternal-infant attachment, parental self-efficacy, infant development. For this experimental study parallel-group randomised control design was used. Data was collected from 64 mother and their infants. The intervention group received the health promotion program in addition to standard care, the control group received only the standard care. Family Information Form, Prenatal Attachment Inventory, Maternal Attachment Inventory, Parenting Self-Efficacy Scale, and Denver II Developmental Screening Tests were used for the collection of the data. Pearson χ2 test, Yates corrected χ2 test, independent t-test, and Mcnemar test were used for analysing the collected data. The groups on maternal-infant attachment (d:1.20 [CI:0.671–1.736]), parental self-efficacy (d:1.37 [CI:0.835 to 1.925]), and development delays of infants (p = .003, C.V: 0.41) were found to be statistically significant. Health promotion program positively influenced the maternal attachment, parental self-efficacy, the development of the infants.IMPACT STATEMENT What is already known on this subject? Pregnancy and postpartum is a difficult period for mothers. Mothers need support. Parenting self-efficacy and maternal attachment are important for improving infant health. Infant should be supported to prevent developmental delays. What do the results of this study add? With the education and support program applied before and after birth, mother and baby were evaluated together and multi-faceted support was provided. What are the implications of these findings for clinical practice and/or further research? Supporting parenting self-efficacy, maternal attachment and infant development should be started during pregnancy and should be continued in the postpartum period

Effects of Imatinib, Nilotinib, Dasatinib on VEGF and VEGFR-1 Levels in Patients with Chronic Myelogenous Leukemia

Objective: Vascular endothelial growth factor (VEGF) is a protein that binding to VEGF receptors 1 (VEGFR-1) and accelerates angiogenesis. The relationship between angiogenesis and progression of tumors were observed in both solid and hematologic cancers. Monoclonal antibodies capable of inhibiting angiogenesis, tyrosine kinase inhibitors use for haematological cancer treatment. In this study; we investigated the effects of Imatinib mesylate (STI-571; Gleevec), Nilotinib (AMN107; Tasigna) and Dasatinib (BMS-354825; Sprycell) on serum levels of VEGF and VEGFR-1, in patients with chronic phase of chronic myeloid leukemia (CML). Method: Serum levels of VEGF and VEGFR-1 were measured in 65 patients with chronic phase of CML. Serum VEGF and VEGFR-1 levels were determined using quantitative sandwich enzyme immunoassay technique according to the manufacturers' instructions. Results: There were 33 (51%) male and 32 (49%) female patients in this study. 38 of 65 patients were using Imatinib, 15 Nilotinib, 12 Dasatinib. Mean serum VEGF and VEGFR-1 levels for the 65 patients with CML were 172.21+/-127.46 pg/mL and 199.62+/-122.22 pg/mL, respectively. In Dasatinib and Imatinib group, serum VEGF and VEGFR-1 levels were significantly higher than in control group (p= 0.008, p< 0.0001, and p< 0.0001, p< 0.0001). In Nilotinib group, serum VEGF levels were higher than control group, but; it was not statistically significant (p= 0.06) while. VEGFR-1 levels were significantly higher than those of controls (p< 0.0001). Conclusion: Imatinib, Nilotinib and Dasatinib were not superior to each other regarding to serum VEGF and VEGFR-1, but it may be said that Nilotinib may has slightly more effect on inhibition of anjiogenesis

Inhibitive effect of N,N'-Dimethylaminoethanol on carbon steel corrosion in neutral sodium chloride solution, at different temperatures

The inhibition of carbon steel corrosion in neutral sodium chloride solution by N,N'- Dimethylaminoethanol (DMEA), at different temperatures, was investigated using weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The results obtained confirm that DMEA is a good organic corrosion inhibitor for carbon steel in 0.5M of NaCl (concentration encountered in the Mediterranean seawater), over the whole range of temperatures studied. The inhibition efficiency (IE%) increases with increasing DMEA concentration; it reaches highest value for a concentration around 0.125 mol.L-1. Potentiodynamic polarization data show that, the compound studied in this research predominantly act as anodic-type inhibitor. The EIS study reveals that the addition of DMEA decreases the corrosion rate of carbon steel in neutral sodium chloride solution, due to the fact that the inhibitor molecules are strongly adsorbed on the active sites following Langmuir isotherm, thus leading to the formation of a stable protective film on the steel surface which is able to keep the metal/solution interface in a passive state. Furthermore, the values of the activation parameters, i.e. ΔHa and Ea obtained in this study indicate that the adsorption process of DMEA is endothermic and could be mainly attributed to chemisorption, respectively

Simultaneous binding of guidance cues NET1 and RGM blocks extracellular NEO1 signaling

During cell migration or differentiation, cell surface receptors are simultaneously exposed to different ligands. However, it is often unclear how these extracellular signals are integrated. Neogenin (NEO1) acts as an attractive guidance receptor when the Netrin-1 (NET1) ligand binds, but it mediates repulsion via repulsive guidance molecule (RGM) ligands. Here, we show that signal integration occurs through the formation of a ternary NEO1-NET1-RGM complex, which triggers reciprocal silencing of downstream signaling. Our NEO1-NET1-RGM structures reveal a "trimer-of-trimers" super-assembly, which exists in the cell membrane. Super-assembly formation results in inhibition of RGMA-NEO1-mediated growth cone collapse and RGMA- or NET1-NEO1-mediated neuron migration, by preventing formation of signaling-compatible RGM-NEO1 complexes and NET1-induced NEO1 ectodomain clustering. These results illustrate how simultaneous binding of ligands with opposing functions, to a single receptor, does not lead to competition for binding, but to formation of a super-complex that diminishes their functional outputs