Intranasal administration of gold nanoparticles functionalized with polyethylene glycol and D1 peptide
Gold nanoparticles (GNP) for therapeutics and diagnostics of central nervous system (CNS) disorders have been extensively reported. However, many in vivo studies have shown that limited quantities of nanoparticles reached the CNS after intravenous (IV) administration and only traces crossed the bloo...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | Chile |
| OAI Identifier: | oai:repositorio.anid.cl:10533/246596 |
| Acceso en línea: | https://hdl.handle.net/10533/246596 |
| Access Level: | acceso abierto |
| Palabra clave: | Medicina y Ciencias de la Salud Medicina Básica Farmacología y Farmacia |
| Sumario: | Gold nanoparticles (GNP) for therapeutics and diagnostics of central nervous system (CNS) disorders have been extensively reported. However, many in vivo studies have shown that limited quantities of nanoparticles reached the CNS after intravenous (IV) administration and only traces crossed the blood-brain barrier (BBB), which is a chief drawback. The intranasal (IN) route has been suggested as a good strategy for circumventing the BBB, but only a few reports related with GNP have been published so far. In this thesis, it has been developed two new gold nanoparticulate systems based on gold nanoprisms and gold nanospheres functionalized with a polyethylene glycol derivative HS-PEG-COOH (PEG) and D1 peptide (GNPr-D1 and GNS-D1, respectively) to evaluate their delivery to the CNS after IN administration. Cell viability assay showed that GNPr-D1 and GNS-D1 were not cytotoxic for concentrations ranging from 0.05 to 0.5 nM. An IN administration of GNPr-D1 and GNS-D1 demonstrated a significant difference between the two types of GNP, in which the latter reached the CNS in higher levels than GNPr-D1. Pharmacokinetic study showed that the peak brain level of gold was 0.75 h after IN administration of GNS-D1. By comparing IN and IV administrations of GNS-D1, it was found that the gold concentrations observed in brain was 55 times higher via the IN route than via IV bolus injection. In contrast, the liver and the spleen were richer with gold by 1470 and 1000-fold 45 min after IV injection. It is concluded, therefore, that the IN route is more effective for targeting gold to the brain than IV administration, apparently by avoiding a systemic exposure. Finally, even though more gold was accumulated in the brain after IN administration, no significant difference was observed between the IN and IV routes in the distribution of GNS-D1 in the various brain areas. |
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