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      1. Author :
        Esposito, Elisabetta; Cortesi, Rita; Drechsler, Markus; Fan, Jie; Fu, Bingmei M.; Calderan, Laura; Mannucci, Silvia; Boschi, Federico; Nastruzzi, Claudio
      2. Title :
      3. Type :
        Journal Article
      4. Year :
      5. Publication :
        European Journal of Pharmaceutics and Biopharmaceutics
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      8. Issue :
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      10. Research Area :
      11. Keywords :
        Solid lipid nanoparticles; Dimethyl fumarate; Brain delivery; Multiple sclerosis; biodistribution; Fluorescent luminescence imaging; IVIS; IVIS FLI in vivo
      12. Abstract :
        Dimethyl fumarate has been demonstrated useful in relapsing remitting multiple sclerosis treatment (Tecfidera®). Nevertheless, since Tecfidera® capsules induce flushing, gastro-intestinal events and other more serious drawbacks, in this investigation a nanoparticle based system to be administered by an alternative way is proposed. In particular this study describes the preparation and characterization of dimethyl fumarate-containing solid lipid nanoparticles (SLN). Namely SLN based on tristearin, tristearin SLN treated with polysorbate 80 and cationic SLN constituted of tristearin in mixture with dimethyldioctadecylammonium chloride were investigated. The effect of the presence of dimethyl fumarate, functionalization by polysorbate 80 and dimethyldioctadecylammonium chloride was studied on morphology and dimensional distribution of SLN, by photon correlation spectroscopy and cryogenic transmission electron microscopy. Dimethyl fumarate release from SLN, studied by Franz cell, evidenced a Fickian dissolutive type kinetic in the case of SLN treated by polysorbate 80. Moreover fluorescent SLN were produced and characterized in order to investigate their in vitro permeability and in vivo biodistribution in mice. An in vitro study of fluorescent SLN permeability performed through a model of mouse brain microvascular endothelial cells, indicated that cationic SLN displayed higher permeability values with respect to neutral SLN and SLN treated by polysorbate 80. Biodistribution of polysorbate 80 treated SLN was studied by fluorescent imaging after intraperitoneal or intranasal administration in mice. The in vivo images indicate that polysorbate 80 treated SLN were able to reach the brain, even if they prevalently accumulated in liver and spleen, especially by intraperitoneal route.
      13. URL :
      14. Call Number :
        PKI @ catherine.lautenschlager @ 13677
      15. Serial :