Karbenoksolon Disodyum İçeren Nanopartikül Formülasyonlarının Tasarımı ve Kortikal Yayılan Depresyona Bağlı Migren Tedavisindeki Etkinliğinin Değerlendirilmesi

Abstract

Recent studies on migraine, one of the most common diseases among neurological diseases, have shown that cortical spreading depolarization waves, cause transient opening of Pannexin-1 mega channels from neuronal cell membrane channel proteins, resulting in an inflammatory response exciting trigeminovascular system, as the cause of headache following aura. Some inhibitors such as carbenoxolone (CBX) have been found to have the potential for relieving pain in migraine by inhibiting these channels. The aim of this thesis is to determine whether CBX disodium, a molecule that cannot pass the Blood Brain Barrier, will be an effective treatment option for migraine prophylaxis by crossing this barrier in the form of surfactant coated poly (lactic-co-glycolic acid) (PLGA) nanoparticle formulation. For this, nanoparticle formulations were designed with Central Composite Design and Artificial Neural Networks models, in vitro characterization and cell culture studies were performed and the in vivo effectiveness in the migraine model related to CSD was evaluated. As a result of the evaluation performed by Scanning Electron Microscopy, it was determined in nanoparticles loaded with CBX disodium had a spherical shape and a smooth surface. The drug was released from CBX disodium loaded nanoparticles within 24 hours. All formulations developed were found to be non-cytotoxic on the Human Cerebral Microvascular Endothelial Cell Line (hCMEC/D3) in cell culture studies. In addition, in vivo studies, it has been found that nanoparticle formulations containing CBX disodium, which are administered intraperitoneally in the CSD model, are more effective compared to the free drug solution.