Effect of microemulsion formulation on biodistribution of ^99mTc-Aprotinin in acute pancreatitis models induced rats

Abstract

Background: Aprotinin is a monomeric globular polypeptide, which derived from bovine lung tissue and theoretically attractive molecule in ameliorating the effects of acute pancreatitis. Acute pancreatitis is an inflammatory condition of the pancreas that is painful and at times deadly. Over the following two decades Aprotinin therapeutic potential on pancreatitis is proven experimentally, its clinical therapeutic success is limited due to low targeting to pancreas.

Objective: The aim of this study was to evaluate the biodistribution of Technetium-99m (^99mTc)-Aprotinin solution (^99mTc-Aprotinin-S) and ^99mTc-Aprotinin loaded microemulsion, which was prepared for the aim of treatment for acute pancreatitis.

Method: Aprotinin was radiolabeled with ^99mTc. Radiochemical purity was determined with radioactive thin layer chromatography studies. ^99mTc-Aprotinin-S and ^99mTc-Aprotinin loaded microemulsion (^99mTc-Aprotinin-M) was administered to acute edematous, severe necrotizing pancreatitis and air pouch model induced rats. Tissue distribution of Aprotinin was investigated with gamma scintigraphy and biodistribution studies.

Results: Aprotinin was radiolabeled by ^99mTc with high radiochemical purity (95.430 ± 0.946%). The complex was found to be stable at room temperature up to 6 h. Animal studies have shown that similar to that of other small proteins Aprotinin is accumulated primarily in the kidney. The scintigraphy and biodistribution studies showed that, while i.v. administration of ^99mTc-Aprotinin-S distributed mostly in kidneys and bladder, ^99mTc-Aprotinin-M, with droplet size of 64.550 ± 3.217 nm, has high uptake in liver, spleen and pancreas.

Conclusion: This might be concluding that microemulsions may be suggested as promising formulations for selectively targeting Aprotinin to pancreas inflammation.

Keywords:

• Aprotinin
• biodistribution
• microemulsion
• pancreatitis
• radiolabeled Aprotinin

Acknowledgements

The authors would like to thank Caglar Us, Ismail Zonguldak, Bulent Ata and Ege University Nuclear Medicine Department technicians for their technical assistance for the animal experiments. Also, the authors would like to thank Ege University Nuclear Medicine Department for their support to supply the radionuclide.

Declaration of interest

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