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  • Title: Aprotinin revisited: formulation, characterization, biodistribution and therapeutic potential of new aprotinin microemulsion in acute pancreatitis.
    Author: Karasulu HY, Oruç N, Üstündağ-Okur N, İlem Özdemir D, Ay Şenyiğit Z, Barbet Yılmaz F, Aşıkoğlu M, Özkılıç H, Akçiçek E, Güneri T, Özütemiz Ö.
    Journal: J Drug Target; 2015; 23(6):525-37. PubMed ID: 25738992.
    Abstract:
    The aim of this study was to develop aprotinin-loaded microemulsion (MA) for intravenous administration and evaluate the biodistribution and therapeutic potential of developed formulation in acute pancreatitis models in rats. Phase diagrams were constructed to identify microemulsion region and the optimal microemulsion was evaluated for physicochemical properties and treatment effect in rats, and comparisons made with the solution of aprotinin (SA). To evaluate the biodistribution of the drug by gamma scintigraphy aprotinin was radiolabeled with (99m)Tc radionuclide. Mild and severe acute pancreatitis was induced in rats by subcutaneous injections of cerulein and introductal infusion of 3% sodium taurocholate into the bile-pancreatic duct, respectively. In addition, serum amylase and pancreatic tissue myeloperoxidase activities were measured to evaluate the pancreatic damage. According to gamma scintigraphy and biodistribution studies, accumulation times and distribution of (99m)Tc-MA and SA were different. While MA was highly uptake by reticuloendothelial system, SA was mostly excreted by kidneys and bladder. Compared with the mild acute pancreatitis group, treatment with MA significantly decreased the serum amylase activity and pancreas myeloperoxidase activity. Furthermore, the protease inhibitor molecule aprotinin has therapeutic potential in acute pancreatitis. Finally, MA may be suggested as a promising alternative for treatment of acute pancreatitis.
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