Enzyme
replacement therapy (ERT) is a therapeutic approach envisioned
decades ago for the correction of genetic disorders, but ERT has been
less successful for the correction of disorders with neurological
manifestations. In this work, we have tested the functionality of
nanoparticles (NP) composed of maltodextrin with a lipid core to bind
and stabilize tyrosine hydroxylase (TH). This is a complex and unstable
brain enzyme that catalyzes the rate-limiting step in the synthesis
of dopamine and other catecholamine neurotransmitters. We have characterized
these TH-loaded NPs to evaluate their potential for ERT in diseases
associated with TH dysfunction. Our results show that TH can be loaded
into the lipid core maltodextrin NPs with high efficiency, and both
stability and activity are maintained through loading and are preserved
during storage. Binding to NPs also favored the uptake of TH to neuronal
cells, both in cell culture and in the brain. The internalized NP-bound
TH was active as we measured an increase in intracellular L-Dopa synthesis
following NP uptake. Our approach seems promising for the use of catalytically
active NPs in ERT to treat neurodegenerative and neuropsychiatric
disorders characterized by dopamine deficiency, notably Parkinson’s
disease