A pharmaceutical study on certain targeted nanodelivery systems PT 4.2.2 / Ahmed Magdy Fatouh ; Supervised Ahmed Abdelbary Abdelrahman , Ahmed Hassen Elshafeey

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutics

Hepatitis C is a viral liver infection caused by hepatitis C virus. In about 80% of the HCV infected patients, chronic liver inflammation occurs which may progress to life-threatening liver conditions like liver cirrhosis and liver cancer. Ledipasvir, one of the direct acting hepatitis C antiviral agents, inhibits NS5A which is non-structural protein playing a crucial role in HCV replication cycle. In combination with sofosbuvir, ledipasvir showed high efficacy in treating HCV but unfortunately its high cost represented an obstacle against its provision to wide population of the HCV infected patients mainly in the developing countries. Our proposed solution to this problem is established upon enhancing ledipasvir uptake into the liver and prolonging its retention within it which can significantly reduce ledipasvir recommended dose and its overall regimen costs. We selected to exploit specific type of receptors expressed on the surface of the targeted hepatocytes called, asialoglycoprotein receptors (ASGPRs) which are characterized by their high affinity towards specific ligands like terminal b-D-galactose and N-acetylgalactosamine groups. To be able to interact specifically with ASGPRs, we planned to develop drug delivery system decorated by galactose residues.The work in this thesis is divided into four chapters as follows: Chapter I: Preparation and evaluation of ledipasvir loaded liposomes.Chapter II: Preparation and evaluation ledipasvir loaded spanlastics. Chapter III:Synthesis, characterization and utilization of galactosylated chitosan. Chapter IVBioavailability study of ledipasvir loaded galactosylated chitosan coated liposomes and spanlastics

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