The (BBB) controls the passage of molecules and cells into the brain. This is crucial for the delivery of drugs in the treatment of central nervous system (CNS) diseases. Nanotechnologies, applied to the drug delivery, offer many advantages over conventional therapeutic methods. The drug suramin, used in the treatment of the peripheral infection during human African trypanosomiasis (HAT), does not cross the BBB and cannot be used to cure the encephalitic stage disease. To achieve the transport of suramin into the brain, using NPs as carriers, and to test in animal model whether this approach could cure HAT CNS infection, is the aim of the present study. The capability to cross the BBB of metal-based NPs and polymer-based NPs, was preliminary carried out. After 24h from iv injection in mice, CaF2 and SrF2 NPs, were observed mostly in liver and spleen, but also in brain parenchyma. Cerium oxide (CeO2) NPs are of special interest since they can exert neuroprotective effects. Their short-term biodistribution was investigated with different techniques, suggesting the largest accumulation in liver and spleen, even if in the brain NP-like elements were observed, exhibiting neuronal morphology. Polymeric PLGA NPs conjugated with a peptide derived from Apolypoprotein E and Prostaglandin-D-synthase, were documented to enter into the brain parenchyma, 2h after the peripheral administration, despite their relative high dimension due to polymeric structure. The present data indicate that metal-based NPs penetration into the brain should also be taken, probably due to their small dimension (~10nm), despite their accumulation in peripheral organs. Possible surface modifications are currently under discussion to overcome macrophage recognition and to improve the blood circulation time. PLGA NPs also reach the CNS, albeit in limited amount; targeting with a peptide seems to improve the BBB crossing for potential brain drug delivery. In parallel, the investigation of CeO2 NPs and PLGA NPs effect on the brain cells was initiated. Glia phenotyping was pursued to reveal astrocytes, using glial fibrillary acidic protein (GFAP) as marker, and antibodies against CD11b, to detect the resident microglia. Both cell types react to the penetration of the tested NPs into the brain, but it remains to be investigated whether this can represent a detrimental or a beneficial response. Direct delivery of suramin into the brain does not cause overt cell damage or inflammatory response in the brain, both in naïve mice and in Tb brucei-infected mice.
Testing nanoparticles for intracerebral drug delivery
Portioli, Corinne
2014-01-01
Abstract
The (BBB) controls the passage of molecules and cells into the brain. This is crucial for the delivery of drugs in the treatment of central nervous system (CNS) diseases. Nanotechnologies, applied to the drug delivery, offer many advantages over conventional therapeutic methods. The drug suramin, used in the treatment of the peripheral infection during human African trypanosomiasis (HAT), does not cross the BBB and cannot be used to cure the encephalitic stage disease. To achieve the transport of suramin into the brain, using NPs as carriers, and to test in animal model whether this approach could cure HAT CNS infection, is the aim of the present study. The capability to cross the BBB of metal-based NPs and polymer-based NPs, was preliminary carried out. After 24h from iv injection in mice, CaF2 and SrF2 NPs, were observed mostly in liver and spleen, but also in brain parenchyma. Cerium oxide (CeO2) NPs are of special interest since they can exert neuroprotective effects. Their short-term biodistribution was investigated with different techniques, suggesting the largest accumulation in liver and spleen, even if in the brain NP-like elements were observed, exhibiting neuronal morphology. Polymeric PLGA NPs conjugated with a peptide derived from Apolypoprotein E and Prostaglandin-D-synthase, were documented to enter into the brain parenchyma, 2h after the peripheral administration, despite their relative high dimension due to polymeric structure. The present data indicate that metal-based NPs penetration into the brain should also be taken, probably due to their small dimension (~10nm), despite their accumulation in peripheral organs. Possible surface modifications are currently under discussion to overcome macrophage recognition and to improve the blood circulation time. PLGA NPs also reach the CNS, albeit in limited amount; targeting with a peptide seems to improve the BBB crossing for potential brain drug delivery. In parallel, the investigation of CeO2 NPs and PLGA NPs effect on the brain cells was initiated. Glia phenotyping was pursued to reveal astrocytes, using glial fibrillary acidic protein (GFAP) as marker, and antibodies against CD11b, to detect the resident microglia. Both cell types react to the penetration of the tested NPs into the brain, but it remains to be investigated whether this can represent a detrimental or a beneficial response. Direct delivery of suramin into the brain does not cause overt cell damage or inflammatory response in the brain, both in naïve mice and in Tb brucei-infected mice.
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