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Intranasal Delivery of Sunitinib: A New Therapeutic Approach for Targeting Angiogenesis of Glioblastoma Publisher Pubmed



Seidkhani E1 ; Moradi F1 ; Rustamzadeh A1 ; Simorgh S2 ; Shirvalilou S3 ; Mehdizadeh M4 ; Dehghani H5 ; Akbarnejad Z6 ; Motevalian M7 ; Gorgich EAC8
Authors
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Authors Affiliations
  1. 1. Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Reproductive Sciences and Technology Research Center, Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Medical Physics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. ENT and Head & Neck Research Center and Department, Hazrat Rasoul Hospital, the Five Senses Institute, Iran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Anatomy, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran

Source: Toxicology and Applied Pharmacology Published:2023


Abstract

Glioblastoma multiforme (GBM) is one of the most vascular among solid tumors, and despite the use of multimodal therapies, the survival of these patients is poor. In order to target angiogenesis in GBM as a promising strategy, an antiangiogenic drug is required. This study was designed to evaluate the effects of sunitinib, a multityrosine kinase inhibitor with tumor proliferation and angiogenesis inhibitory properties, on GBM-bearing rats. Given the ineffective drug delivery to the brain due to the presence of the blood-brain barrier (BBB), intra-nasal (IN) drug delivery has recently been considered as a non-invasive method to bypass BBB. Therefore, in the current study, IN was used as an ideal method for the delivery of sunitinib to the brain, and the effects of this method were also compared to the OR administration of the sunitinib. GBM was induced in the brain of male Wistar rats, and they were randomly divided into 4 groups; IN-STB (sunitinib intranasal delivery), IN-sham (placebo intranasal delivery), OR-STB (sunitinib oral delivery) and OR-sham (placebo oral delivery). After the end of the treatment period, an MRI of animals' brains showed a reduction in tumor growth in the treatment groups. Immunohistochemistry revealed that sunitinib inhibits angiogenesis in GBM in both OR and IN delivery methods. Analysis of liver tissue and enzymes showed that IN delivery of sunitinib had less hepatotoxicity than the OR method. Overall, it was found that IN sunitinib delivery could be used as a potential non-hepatotoxic alternative for the treatment of GBM. © 2023 Elsevier Inc.
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