Favipiravir Yüklü Lipozom Formülasyonlarının Hazırlanması ve İn-Vitro Değerlendirilmesi

Abstract

COVID-19 disease has been declared as a pandemic all over the World. Severe pneumonia caused the death of approximately 6.5 million people in its course. Today, treatment protocols are still limited and there is not specific and effective treatment method yet. With in this scope, it has been observed that the use of Favipiravir (FVP) has positive effects on the improvement of the course of the disease in R&D studies and clinical trials conducted in the world. FVP is an antiviral drug that selectively and potently inhibits the RNA-dependent RNA polymerase (RdRP) of influenza and many other RNA viruses. It is among the treatments that reduce virus replication. However, due to its low solubility properties and both metabolization and inhibition by aldehyde oxidase, an initial oral loading dose is required to achieve adequate blood levels in the body and side effects are observed in patients after high doses for treatment. Over the last decades, studies on increasing the effectiveness of antiviral compounds have increased with nanotechnological approaches. New formulations are under way that could be used to treat effective substanes with the benefits of nanocarriers. Nanoliposomes are very prominent among these systems because of their advantages, including superior biocompatibility, resolution and increasing cell penetration. In view of this information, the study of formulation optimization was primarily conducted in thesis, and the FVP-loaded nanoliposome (FVP-NL) formulations were prepared using different lipid derivatives (Lipoid S100, L-α-phosphotidilcholine, Phospholipon 90G and DPPC) and organic phases (ethanol and chloroform). As a result of the characterization studies, the formulation of the nanoliposome prepared in the phospholypon 90 G and chloroform organic phase (PB:120.6±4.378; EE: 76.50±1.27%) was observed to be homogeneous (PDI:0.280±0.038) and stable (ZP:30.6±1.48).In vitro release and Franz diffusion studies, an extended release profile was obtained, and it was found to diffuse over longer periods of time than the commercial preparation of the FVP.Following studies of cytotoxicity, antiviral activity was carried out on the Vero E6 cell line infected with SARS-CoV-2 to determine the effectiveness of the formulation. The IC50 of the FVP-NL was detected at 1,147 mM. As a result, the thesis study developed an innovative nanoliposome formulations that is effective and reliable to eliminate the disadvantages of current treatments. For further studies it is planned that these formulations will be used in capsule for treatment of COVID-19 disease, and to carry out studies for oral and/or inhaler administration.