Nanoparticles for targeted drug delivery to glial cells after brain ischemia

VERONICA MURTA; PRISCILA SCHILRREFF; MARIANA SEIB; MARÍA JOSÉ MORRILLA; ALBERTO JAVIER RAMOS

Huerta Grande, Córdoba

Congreso; XXIX CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS; 2014

Sociedad Argentina de Neurociencias

During the last years, mounting evidence has shown that glial conversion into the proinflammatory phenotype occurring after brain injury is associated with increased neurodegeneration. Necrotic cells release specific DAMP (ie. S100B, HMGB-1) that induce neuroinflammation by the activation of NFkB-dependent pathways in glia. Unfortunately, global NFkB blockage is not neuroprotective since it seriously affects neuronal survival. Some polyamidoamine (PAMAM) dendrimers were shown to be incorporated specifically by glial cells. Our project aims to design nanoparticles suitable for targeted drug delivery to reactive glial cell in order to prevent glial conversion into the proinflammatory-neurodegenerative phenotype. In the present work we tested different types of dendrimers and liposomes and we found that a new type of core-shell tectodendrimer (G5G2.5 PAMAM) is time- and dose-dependently incorporated by primary astrocytes and microglia, but not by hippocampal neurons co-cultured with glia. The exposure to oxygen and glucose deprivation (OGD), an in vitro model of ischemia, specifically increased astroglial uptake of the G5G2.5-FITC dendrimer. In vivo, increased uptake of the dendrimer was observed in the ipsilateral hemisphere after ischemia by cortical devascularization. In conclusion, the G5G2.5 showed a marked preference for astroglia and microglia in vitro and in vivo, making it suitable as a specific drug carrier for glial cells.