Curcumin (Cur)[1], a natural polyphenol compound, has been found to exert anti-inflammatory, antioxidant, anti-apoptotic and anti-amyloid-? (A?) aggregation effects on Central Nervous System (CNS) diseases. Nose to brain delivery represents a promising non-invasive strategy to carry substances to brain bypassing blood brain barrier (BBB), reducing systemic biodistribution and increasing patient compliance. The aim of this study was to develop Cur loaded nanoparticles (polymeric, PNP, and lipidic, SLN) for nose to brain delivery to improve brain targeting. The encapsulation of Cur in polylactic-co-glycolic acid (PLGA) nanoparticles or in SLN was also designed to increase its aqueous solubility and stability. Two nanosuspensions were selected by previously screening and studied for this purpose: PNP, obtained by nanoprecipitation, and SLN[2], obtained by modification of the emulsification-solvent diffusion technique. PCS analysis revealed that both PNP and SLN had a mean size of 300 and 130 nm, respectively; high homogeneity and negative zeta potential. Incorporation of Cur into nanocarriers increased aqueous solubility and stability of the drug as showed by performed stability tests until 6 days at different temperatures. Since the toxicity of a nanoparticulate formulations directed to the brain is very important criteria for its safety, the cytotoxicity studies of PNP and SLN were previously carried out in rat Olfactory Ensheanting Cells (OECs) and astrocytes. We tested free Cur, and both unloaded and Cur loaded nanosuspensions; cell viability tests (MTT) were performed at 24, 72, 168 hrs on cells. To evaluate the protective effect of Cur we used an in vitro approach by culturing both OECs and astrocytes under condition of hypoxia. Subsequently, cultures were processed by immunocytochemistry and cell viability was evaluated by MTT assay. In vivo studies on healthy rats were carried out to verify Cur loaded NPs localization in the brain after intranasal administration. Twenty-four hours after nose delivery fluorescence images showed that both Cur loaded PNP and SLN were localized into rostral brain regions (i.e. frontal cerebral cortex and hippocampus), whereas a very light labeling was found in the caudal cerebral regions (i.e. cerebellum).
Potential neuroprotection effect and increase of stability of curcumin loaded
Rosalia Pellitteri;
2015
Abstract
Curcumin (Cur)[1], a natural polyphenol compound, has been found to exert anti-inflammatory, antioxidant, anti-apoptotic and anti-amyloid-? (A?) aggregation effects on Central Nervous System (CNS) diseases. Nose to brain delivery represents a promising non-invasive strategy to carry substances to brain bypassing blood brain barrier (BBB), reducing systemic biodistribution and increasing patient compliance. The aim of this study was to develop Cur loaded nanoparticles (polymeric, PNP, and lipidic, SLN) for nose to brain delivery to improve brain targeting. The encapsulation of Cur in polylactic-co-glycolic acid (PLGA) nanoparticles or in SLN was also designed to increase its aqueous solubility and stability. Two nanosuspensions were selected by previously screening and studied for this purpose: PNP, obtained by nanoprecipitation, and SLN[2], obtained by modification of the emulsification-solvent diffusion technique. PCS analysis revealed that both PNP and SLN had a mean size of 300 and 130 nm, respectively; high homogeneity and negative zeta potential. Incorporation of Cur into nanocarriers increased aqueous solubility and stability of the drug as showed by performed stability tests until 6 days at different temperatures. Since the toxicity of a nanoparticulate formulations directed to the brain is very important criteria for its safety, the cytotoxicity studies of PNP and SLN were previously carried out in rat Olfactory Ensheanting Cells (OECs) and astrocytes. We tested free Cur, and both unloaded and Cur loaded nanosuspensions; cell viability tests (MTT) were performed at 24, 72, 168 hrs on cells. To evaluate the protective effect of Cur we used an in vitro approach by culturing both OECs and astrocytes under condition of hypoxia. Subsequently, cultures were processed by immunocytochemistry and cell viability was evaluated by MTT assay. In vivo studies on healthy rats were carried out to verify Cur loaded NPs localization in the brain after intranasal administration. Twenty-four hours after nose delivery fluorescence images showed that both Cur loaded PNP and SLN were localized into rostral brain regions (i.e. frontal cerebral cortex and hippocampus), whereas a very light labeling was found in the caudal cerebral regions (i.e. cerebellum).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
