Insights into kinetics, release, and behavioral effects of brain-targeted hybrid nanoparticles for cholesterol delivery in Huntington's disease

Supplementing brain cholesterol is emerging as a potential treatment for Huntington's disease (HD), genetic neurodegenerative disorder characterized, among other abnormalities, by inefficient biosynthesis. However, delivering to the challenging due blood-brain barrier (BBB), which prevents it from reaching striatum, especially, with therapeutically relevant doses. Here we describe distribution, kinetics, release, and safety of novel hybrid polymeric nanoparticles made PLGA were modified an heptapeptide (g7) BBB transit (hybrid-g7-NPs-chol). We show that these NPs rapidly reach target neural cells. Moreover, deuterium-labeled hybrid-g7-NPs-chol released in controlled manner within accumulates over time, while being removed peripheral tissues plasma. confirm systemic repeated injections new enhanced endogenous biosynthesis, prevented cognitive decline, ameliorated motor defects HD animals, without any inflammatory reaction. In summary, this study provides insights about benefits delivery through advanced brain-permeable treatment.