Preparation of Ternary Non-Viral Vectors for Central Nervous System Disorders

Abstract

The use of nanosystems for the treatment of brain disorders, like cancer, has emerged in recent years. In this project, a ternary system based on poly(lactic-co-glycolic acid) (PLGA), chitosan and 2’-deoxy-5-fluorouridine (FdU) has been engineered as a promising non-viral vehicle in which all the components interact via electrostatic forces. The goal is to find a strategy to transport FdU, which acts as a therapeutic molecule. We hypothesised that our system, owing to its nanometric properties, might go through the blood-brain barrier (BBB). A formulation composition in which the nanosystem is stable has been found, exhibiting a small diameter, low polydispersity index values and a positive ζ-potential. We demonstrated that tumour cells were able to take up our nanosystem, according to flow cytometry analyses. In addition, MTT assays indicate that the nanosystem displays certain degree of toxicity in cancer cells. Trans-Ferulic acid (FA) was encapsulated in PLGA NPs and 50% of the drug was released gradually after 9 hours