Aprotinin revisited: formulation, characterization, biodistribution and therapeutic potential of new aprotinin microemulsion in acute pancreatitis

Abstract

The aim of this study was to develop aprotinin-loaded microemulsion (M_A) 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 (S_A). To evaluate the biodistribution of the drug by gamma scintigraphy aprotinin was radiolabeled with ^99mTc 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 ^99mTc-M_A and S_A were different. While M_A was highly uptake by reticuloendothelial system, S_A was mostly excreted by kidneys and bladder. Compared with the mild acute pancreatitis group, treatment with M_A significantly decreased the serum amylase activity and pancreas myeloperoxidase activity. Furthermore, the protease inhibitor molecule aprotinin has therapeutic potential in acute pancreatitis. Finally, M_A may be suggested as a promising alternative for treatment of acute pancreatitis.

• Aprotinin
• microemulsion
• ^99mTc-aprotinin
• mild acute pancreatitis
• severe acute pancreatitis

Acknowledgements

The authors would like to thank to Ege University, Faculty of Pharmacy, Department of Microbiology and Department of Toxicology. The authors would like to thank Assoc. Prof. Dr. Timur Köse for statistical advice and Çağlar Us, İsmail Zonguldak, Bulent Ata for assistance at in vivo experiments.

Declaration of interest

The authors declare no conflict of interest. The authors alone are responsible for the content and writing of the paper. This study was supported by The Scientific and Technological Research Council of Turkey (Tübitak 108S083). The authors also would like to thank to the T.R. Prime Ministry State Planning Organization Foundation (Project Number: 09DPT001).