Background: Using imatinib, a tyrosine kinase inhibitor drug used in lymphoblastic leukemia, has
always had limitations due to its cardiotoxicity and hepatotoxicity side effects. The objective of this study is to
develop a target-oriented drug carrier to minimize these adverse effects by the controlled release of the drug.
Methods: KIT-5 nanoparticles were functionalized with 3-aminopropyltriethoxysilane and conjugated to rituximab
as the targeting agent for the CD20 positive receptors of the B-cells. Then they were loaded with imatinib
and their physical properties were characterized. The cell cytotoxicity of the nanoparticles was studied by MTT
assay in Ramos (CD20 positive) and Jurkat cell lines (CD20 negative) and their cellular uptake was shown by
fluorescence microscope. Wistar rats received an intraperitoneal injection of 50 mg/kg of the free drug or targeted
nanoparticles for 21 days. Then the level of aspartate Aminotransferase (AST), alanine Aminotransferase
(ALT), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH) were measured in serum of animals. The
cardiotoxicity and hepatotoxicity of the drug were also studied by hematoxylin and eosin staining of the tissues.
Results: The targeted nanoparticles of imatinib showed to be more cytotoxic to Ramos cells rather than Jurkat
cells. The results of the biochemical analysis displayed a significant reduction in AST, ALT, ALP, and LDH
levels in animals treated with targeted nanoparticles, compared to the free drug group. By comparison with the
free imatinib, histopathological results represented less cardiotoxicity and hepatotoxicity in the animals, which
received the drug through the current designed delivery system.
Conclusion: The obtained results confirmed that the rituximab targeted KIT-5 nanoparticles are promising in
the controlled release of imatinib and could decrease its cardiotoxicity and hepatotoxicity side effects.