Development and in vitro evaluation of drug delivery systems for NOSE-TO-brain drug administration

Depression, a mood disorder, is an illness that affects approximately 265 million people worldwide, resulting in reduced quality of life, and behavioral disturbances as well as feelings and thoughts. Most drugs used to treat depression increase the availability of monoamines at synapses by various mechanisms. However, antidepressants' therapeutic efficacy depends on their sustained and prolonged presence at the site of action in the brain. Today, antidepressants are generally used orally. But there are many obstacles on the way to achieve the desired effect. These include poor absorption, poor first-pass hepatic bioavailability, drug toxicity and dose-related side effects. In addition, another reason for the failure of the treatment process on patients with depression is the presence of the blood-brain barrier, via preventing the transition of drugs to the central nervous system. Intranasal applications are considered as an effective and feasible alternative to overcome all these difficulties. Nanoparticulate drug delivery systems that are directly targeted from the nose to the brain, ensure that the active substance is directly delivered to the target area and thus increase the effectiveness in the treatment of these diseases. In this thesis study; lipid-polymer-based nanoparticle drug carrier systems of paroxetine, a selective serotonin reuptake inhibitör, which selected as a model active substance were prepared. Optimum formulations were determined by determining the characterization, stability and in vitro release properties of the prepared formulations. The cytotoxic effects and permeability of pure active substance and selected paroxetine containing Nanoparticles were evaluated by cell culture studies performed on the Caco-2 cell line.