Fluorosurfactants for medical nanoemulsions, their surface-active and biological properties.

Nano- and microemulsions have found various applications in pharmaceutical and medical areas both in research field as well as in applied solutions for drug delivery or diagnostic agents. However, production of stable and bio- / hemocompatible nanoemulsions are still challenging. New group of ionic surfactants have been synthesized with perfluorohexyl- or perfluorooctyl-groups as hydrophobic tail. The CMC and the parametres of the O/W emulsion (the particle size distribution and the zeta-potential) were determined. The influence of the surfactants on in vitro proliferation of human endothelial cell lines HMEC-1, murine fibroblasts L929 and hemolysis were investigated as characteristic for biocompatibility. Three candidates of surfactants were selected for pre-clinical tests on a small animal model (adult Sprague Dawley rats) on the basis of preliminary studies. This allowed to obtain nanoemulsions with narrow droplets size (average droplet diameter 141-147 nm with PDI index 0.059 - 0.065) and showed better stability over time in comparison to the commercially available surfactants. Neither cytotoxic nor hemolytic potential were observed during incubation of obtained fluorosurfactans with model cell lines L929 and HMEC-1 (average cell viability above 85 % after incubation with 1% solutions) and erythrocytes (hemolysis rate below 3.1 % for all 0.5 % solutions). During acute toxicity test on rat model, it was found that all three tested surfactant solutions showed no significant differences in controlled parameters and survival rate with control group (p > 0.05). Presented surfactants are dedicated but not limited to emulsification of organic fluorocompounds.

Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration.

BACKGROUND: The skeletal muscle reconstruction occurs thanks to unipotent stem cells, i.e., satellite cells. The satellite cells remain quiescent and localized between myofiber sarcolemma and basal lamina. They are activated in response to muscle injury, proliferate, differentiate into myoblasts, and recreate myofibers. The stem and progenitor cells support skeletal muscle regeneration, which could be disturbed by extensive damage, sarcopenia, cachexia, or genetic diseases like dystrophy. Many lines of evidence showed that the level of oxygen regulates the course of cell proliferation and differentiation. METHODS: In the present study, we analyzed hypoxia impact on human and pig bone marrow-derived mesenchymal stromal cell (MSC) and mouse myoblast proliferation, differentiation, and fusion. Moreover, the influence of the transplantation of human bone marrow-derived MSCs cultured under hypoxic conditions on skeletal muscle regeneration was studied. RESULTS: We showed that bone marrow-derived MSCs increased VEGF expression and improved myogenesis under hypoxic conditions in vitro. Transplantation of hypoxia preconditioned bone marrow-derived MSCs into injured muscles resulted in the improved cell engraftment and formation of new vessels. CONCLUSIONS: We suggested that SDF-1 and VEGF secreted by hypoxia preconditioned bone marrow-derived MSCs played an essential role in cell engraftment and angiogenesis. Importantly, hypoxia preconditioned bone marrow-derived MSCs more efficiently engrafted injured muscles; however, they did not undergo myogenic differentiation.