Targeted PLGA nanocarriers for brain drug delivery

The role of the blood-brain barrier (BBB) in controlling passage of molecules and cells is crucial to maintain the homeostatic brain environment. This, however, represents a limiting factor for treatment of central nervous system (CNS) diseases. Nanotechnologies applied to drug delivery are currently contributing to overcome this issue. We here tested the capability of biocompatible and biodegradable PolyD,L-Lactide-co-Glycolide Acid (PLGA) nanoparticles (NPs) to cross the BBB. The ultimate goal of this study is to identify NPs that could transport across the BBB the trypanocydal drug suramin to cure a severe brain infection. PLGA NPs were conjugated with a peptide derived from Apolypoprotein E and Prostaglandin-D-synthase to target their penetration of the BBB, despite their relative large size. For their visualization, the NPs were also conjugated with the fluorochrome FITC. Following iv injections, fluorescently labeled PLGA NPs were found in the brain parenchyma at 2h (but not at 24h given their rapid degradation). Multiple labeling revealed their localization mostly on neuronal and microglial cell membranes besides the extracellular space. No signs of neuronal cell death were found up to 24h from administration. Immunophenotyping revealed a mild activation of astrocytes and microglia. It remains to be investigated whether the glial cell response represents a detrimental or beneficial response, and the potential occurrence of neurotoxic effects over time. The data indicate that the custom-made PLGA NPs under study could provide potential nanocarriers for targeted brain delivery of drugs. Further experiments are in progress. The support of the “Verona Nanomedicine Initiative” is gratefully acknowledged.