(2020) Encapsulation of Imatinib in Targeted KIT-5 Nanoparticles for Reducing its Cardiotoxicity and Hepatotoxicity. Anti-Cancer Agents in Medicinal Chemistry. pp. 1966-1980. ISSN 1871-5206
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Abstract
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.
Item Type: | Article |
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Keywords: | Imatinib rituximab KIT-5 cardiotoxicity hepatotoxicity lymphoblastic leukemia CHRONIC MYELOID-LEUKEMIA ACUTE LYMPHOBLASTIC-LEUKEMIA TYROSINE KINASE INHIBITORS STEM-CELL TRANSPLANTATION BCR-ABL INTERIM THERAPY MESYLATE RITUXIMAB DELIVERY DOXORUBICIN |
Subjects: | QV Pharmacology |
Divisions: | Faculty of Pharmacy and Pharmaceutical Sciences > Department of Clinical Pharmacy and Pharmacy Practice Faculty of Pharmacy and Pharmaceutical Sciences > Department of Pharmaceutical Biotechnology Faculty of Pharmacy and Pharmaceutical Sciences > Department of Pharmacotherapy Novel Drug Delivery Systems Research Center Other |
Page Range: | pp. 1966-1980 |
Journal or Publication Title: | Anti-Cancer Agents in Medicinal Chemistry |
Journal Index: | ISI |
Volume: | 20 |
Number: | 16 |
Identification Number: | https://doi.org/10.2174/1871520620666200619174323 |
ISSN: | 1871-5206 |
Depositing User: | Zahra Otroj |
URI: | http://eprints.mui.ac.ir/id/eprint/13846 |
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