Synthesys and characterization of phenytoin loaded solid lipid nanoparticles for use in the threatment of epilepsy

Epilepsy is a chronic neurological disease that affects 1% of the world's population and is characterized by spontaneous recurrent seizures. Common causes include pathogenic genetic variants in critical neuronal genes, traumatic brain injuries, infection, and developmental malformations with or without genetic support. Although various drugs are used in the treatment of epilepsy, these drugs do not treat epilepsy, they only prevent seizures. For this reason, such drugs used in the treatment of epilepsy are known as anticonvulsants. One of the most widely used anticonvulsants is phenytoin. Phenytoin has a high protein binding capacity, and at doses where phenytoin has anti-seizure effects, its protein binding property increases the side effect of phenytoin. Although this situation has a high anti-seizure effect, the use of phenytoin in epilepsy patients has decreased considerably today. Today, the combination of conventionally defined therapeutics with nanoparticles carrier systems in order to increase their bioavailability / decrease their side effects is one of the subjects studied. The main advantages of nanoparticles are; (1) improved bioavailability by increasing water solubility, (2) increased resistance time in the body (increasing half-life for clearance/increased specificity for cognate receptors), and (3) targeting the drug to a specific site (site of action). Thus, by causing a simultaneous decrease in the required amount of drug and dose toxicity, it ensures the safe delivery of toxic therapeutic drugs and the protection of non-target cells and tissues from serious side effects. Considering that free phenytoin clings to protein in vivo, becomes dysfunctional, does not dissolve in water, and causes significant side effects in case of high doses, phenytoin is used in the treatment of epilepsy again with nanoparticular systems, which have recently been used as a drug carrier and for controlled release in order to prevent such situations. anticipated to be used. For this purpose, the in vitro characterization of phenytoin encapsulated in stearic acid nanoparticles will be performed and its effects on glial and neuronal cells will be examined in our project proposal. For this purpose, an in vitro epilepsy model will be created in the T98G gliablastoma cell line and the changes that occur in cells as a result of the interaction of these models with drug-loaded nanoparticles will be examined (TOS and 8-OHdG). Keywords: Epilepsy, Phenytoin, Solid Lipid Nanoparticles, TOS, 8-OHdG