As it is well known, the blood-brain barrier (BBB) plays a protective role, limiting the access of molecules and cells into the brain. In recent years different types of nanoparticles (NPs) have been investigated for the delivery of drugs to a specific target site, also to treat brain pathological conditions. Suramin, a polysulfonate naphthylurea, is a drug used for the early-stage therapy of human African trypanosomiasis (HAT), a neglected disease also known as sleeping sickness. HAT is a severe central nervous system infection caused by the extracellular parasite Trypanosoma brucei (Tb, transmitted by tsetse flies as vectors). Suramin does not cross the BBB and is therefore ineffective once the parasites have invaded the brain. Only highly toxic arsenical compounds are currently available to cure second stage HAT, which is fatal if left untreated. The aim of this study is the delivery of suramin across the BBB using NPs as carriers, to find alternative therapeutic approaches that are urgently needed in the treatment of HAT. To reach this goal, different types of nanocarriers have been tested in vitro and in vivo. Cell viability test with CaF2 and SrF2 NPs, conjugated with lanthanide dopant ions, pointed out a toxicity of these NPs in a stabilized cell line of pure motor neurons (NSC-34) available in our laboratory. In vivo trials (in C57/BL mice) were conducted with different NPs, investigating their biodistribution with confocal microscopy. In the case of Cerium oxide NPs, the densest accumulation was found in liver and spleen after 24 h, with little or no penetration in the brain in the initial in house preparation of these NPs, which showed considerable aggregation. PolyD,L-Lactide-co-Glycolide Acid (PLGA) NPs conjugated with Prostaglandin D synthetase were found, 24 h after iv injection, in the brain of Tb brucei-infected mice (model of HAT infection). Testing other types of nanocarriers, such as carbon- nanotubes and PLGA NPs functionalized with peptide derived from ApoE, are currently ongoing. In parallel, the central effects of suramin, delivered via intracerebroventricular injection, have been investigated as a basis for the delivery of this drug with nanosystems. No tissue damage or glial cell activation was observed in the brain after histochemical and immunohistochemical analyses, encouraging efforts for a targeted delivery of this drug across the blood-brain barrier.
Testing nanoparticles for intracerebral drug delivery.
Portioli, Corinne
2013-01-01
Abstract
As it is well known, the blood-brain barrier (BBB) plays a protective role, limiting the access of molecules and cells into the brain. In recent years different types of nanoparticles (NPs) have been investigated for the delivery of drugs to a specific target site, also to treat brain pathological conditions. Suramin, a polysulfonate naphthylurea, is a drug used for the early-stage therapy of human African trypanosomiasis (HAT), a neglected disease also known as sleeping sickness. HAT is a severe central nervous system infection caused by the extracellular parasite Trypanosoma brucei (Tb, transmitted by tsetse flies as vectors). Suramin does not cross the BBB and is therefore ineffective once the parasites have invaded the brain. Only highly toxic arsenical compounds are currently available to cure second stage HAT, which is fatal if left untreated. The aim of this study is the delivery of suramin across the BBB using NPs as carriers, to find alternative therapeutic approaches that are urgently needed in the treatment of HAT. To reach this goal, different types of nanocarriers have been tested in vitro and in vivo. Cell viability test with CaF2 and SrF2 NPs, conjugated with lanthanide dopant ions, pointed out a toxicity of these NPs in a stabilized cell line of pure motor neurons (NSC-34) available in our laboratory. In vivo trials (in C57/BL mice) were conducted with different NPs, investigating their biodistribution with confocal microscopy. In the case of Cerium oxide NPs, the densest accumulation was found in liver and spleen after 24 h, with little or no penetration in the brain in the initial in house preparation of these NPs, which showed considerable aggregation. PolyD,L-Lactide-co-Glycolide Acid (PLGA) NPs conjugated with Prostaglandin D synthetase were found, 24 h after iv injection, in the brain of Tb brucei-infected mice (model of HAT infection). Testing other types of nanocarriers, such as carbon- nanotubes and PLGA NPs functionalized with peptide derived from ApoE, are currently ongoing. In parallel, the central effects of suramin, delivered via intracerebroventricular injection, have been investigated as a basis for the delivery of this drug with nanosystems. No tissue damage or glial cell activation was observed in the brain after histochemical and immunohistochemical analyses, encouraging efforts for a targeted delivery of this drug across the blood-brain barrier.
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