Testing nanocarriers for targeted brain drug delivery.

Targeted delivery of drugs to the brain is one of the most difficult tasks in neuroscience since the blood-brain barrier (BBB) acts as very selective filter, blocking the vast majority of molecules and compounds. We have here investigated, in vitro and in vivo, different types of nanocarriers with the ultimate goal to transport across the BBB the trypanocydal drug suramin, in the attempt to cure the encephalitic stage of a severe infection caused by the extracellular parasites African trypanosomes (only very toxic drugs are currently available for this disease). To this purpose, we have studied on one hand the response of the brain parenchyma to direct intracerebral administration of suramin, which did not elicit neurotoxic effects, encouraging further efforts. On the other hand, we have investigated, with different techniques, the biodistribution of different types of nanoparticles (NPs). CaF2 and SrF2 NPs and fluorescently-tagged nanoceria (cerium oxide NPs) have been analyzed with electron microscopy, confocal microscopy and mass spectrometry. For both these types of metal-based NPs, after iv injections in mice, we have observed a short-term accumulation in the liver and spleen, with little penetration in the brain. Preliminary promising results have instead been obtained with PolyD,L-Lactide-co-Glycolide Acid (PLGA), a biocompatible and biodegradable polymer, functionalized with a peptide derived from ApoE. With this strategy, which was here used for the first time, fluorescently labeled PLGA NPs have been observed within the brain parenchyma. Further experiments are currently in progress. The support of the “Verona Nanomedicine Initiative” is gratefully acknowledged.