In this work, we prepared and characterized biodegradable nanoparticles based on a PLGA copolymer matrix in order to encapsulate PHA as a novel strategy to improve its permeability and delivery to the CNS for the treatment of neurodegenerative disorders, mainly TDP-43 proteinopathies such as ALS or FTD. The gene discussed is TARDBP; the disease is frontotemporal dementia.