Aim: To validate the use of ultrafiltration (UF) as an alternative applicable industrial method to replace ultracentrifugation (UC) in the purification of mesenchymal stromal cell (MSC)-secretome. Materials & methods: Pharmaceutical formulations containing secretome and/or extracellular vesicles were extracted from adipose-MSCs and bone marrow-MSCs by combining UF or UC with lyophilization. Results & conclusion: UF led to higher protein, lipid, cytokine and exosomes yields compared with UC. The isolation procedure and cell source influenced immunomodulatory activity, which was in vitro evaluated by inhibition of phytohemagglutinin-activated peripheral blood mononuclear cell proliferation, and by modulation of IL-10, IFN-γ and IL-6. A secretome dosage was identified to obtain the same immunomodulatory activity of MSCs, paving the way for cell-free therapy.
The effect of ternary complexation of naproxen, a poorly water soluble anti-inflammatory drug, with hydroxypropyl-beta-cyclodextrin and the basic aminoacid L-arginine on the drug dissolution properties has been investigated. Equimolar binary (drug-cyclodextrin or drug-arginine) and ternary (drug-cyclodextrin-arginine) systems were prepared by blending, cogrinding, coevaporation, and characterized by differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy, X-ray diffractometry. The dissolution behavior of naproxen from the different products was evaluated by means of a continuous flow through method. The results of solid state studies indicated the presence of strong interactions between the components in ternary coevaporated and coground systems, which were both of totally amorphous nature. In contrast, the presence of either free drug or free arginine was detected when the third component (cyclodextrin or aminoacid) was physically mixed, respectively, to the drug-arginine binary system (as physical mixture, coevaporate, or coground product) or to the drug-cyclodextrin binary system (as physical mixture, coevaporate, or coground product). All ternary combinations were significantly (P<0.001) more effective than the corresponding binary drug-cyclodextrin and drug-arginine systems in improving the naproxen dissolution rate. The best performance in this respect was given by the ternary coevaporate, with about 15 times increase in terms of both drug relative dissolution rate and dissolution efficiency. The synergistic effect of the simultaneous use of arginine and cyclodextrin on the dissolution rate of naproxen was attributed to the combined effects of inclusion in cyclodextrin and salt formation, as well as to a specific role played by arginine in this interaction.
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