Synthesis, characterization and investigation of biodistribution of dendrimer-amiloride nanoconjugate using single photon computed tomography technique in animal sample

Document Type : Research Paper

Authors

1 Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Revolution Square, 16 Azar St, Tehran, Iran

2 Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Lorestan University of Medical Sciences, Khorramabad, Iran

Abstract

Objective(s): Amiloride is a pyrazine compound that inhibits the reabsorption of sodium by blocking sodium channels in the cells of the renal cortex. It has demonstrated promising efficacy in the treatment of cancer in recent times. This study assessed the in vivo biodistribution of amiloride conjugated to dendrimer as a targeted agent utilizing SPECT imaging.
Materials and Methods: The dendrimer was synthesised using polyethylene glycol and citric acid as precursors, and dicyclohexyl carbodiimide as a zero-order crosslinker. Amiloride was then conjugated to the dendrimer through the terminal amine group, forming an amide bond with the acidic group of the dendrimer. The synthetic particles were assessed by characterization techniques including FTIR, TEM, LC-Mass, and MAP. The response surface optimization method based on the core chemical was employed to achieve maximum labelling efficiency.  The ideal circumstances and biodistribution in the in vivo environment were assessed. 
Results: TThe characterization findings demonstrated the effective formation and linkage of the nanoconjugate. The Radiochemical purity (RCP) of the dendrimer-amiloride complexes with Technetium-99m, achieved under ideal conditions (28 minutes of incubation, 1.4 units of reduced agent, and 17.5 mg of dendrimer-amiloride), exceeds 90%. This demonstrates the considerable potential of dendrimer-amiloride in forming complexes with Technetium-99m. The results from imaging and biodistribution tests showed that 99mTc-dendrimer–amiloride had a high level of activity (7.8 %ID/g) at the tumor site. This was due to the increased expression of sodium channel. 
Conclusion: The favorable characteristics and conduct of the produced nanoprobe indicate its potential as an innovative tool for the advancement of radiopharmaceutical-based medication. Furthermore, it has the capacity to envision a broad spectrum of malignancies.

Keywords

References

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Nanomedicine Journal
Volume 11, Issue 3
July 2024
Pages 332-341

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