Preparation and in vitro- in vivo evaluation of biotechnological drug compound loaded formulation for the treatment of huntington's disease

Huntington's disease is a neurodegenerative disease specific to the central nervous system, the pathogenesis of which is well understood. This disease, which generally begins to show its effects in the 30s, and whose age of onset changes inversely with the amount of CAG trinucleotides in the IT15 gene, first impairs psychiatric, then motor and finally cognitive activities. The most prominent pathological feature of the disease is the death of strial neurons in the basal ganglia of the brain. With the progression of the disease, neuron death appears in almost all parts of the brain. Current treatment methods of the disease are only symptomatic and therefore may be preferred for a temporary period. There is a need for treatments that will modify the progression of Huntington's disease. In our study, the pathogenesis of the disease was modified by loading disease-specific siRNAs on chitosan and poly beta aminoester nanoparticles targeted to strial neurons in the brain. Both siRNA-loaded and blank formulations were characterized. Ideal formulations (F1-NMDA, D-NMDA, K1-PEG-NMDA, K2-PEG-NMDA and K3-PEG-NMDA) were tested on SH-SY5Y and Neuro-2A cell lines, and in vivo studies have been carried out YAC128 transgenic mice. Mice were administered intranasally and intraperitoneally. As a result of studies, the F1-NMDA formulation was found to silence more than 60% of genes.