BRAIN-TARGETED DELIVERY OF ANDROGRAPHOLIDE USING SOLID LIPID NANOPARTICLES: IN VITRO AND IN VIVO EVALUATION

Andrographolide (AG) is the major diterpenoid of Andrographis paniculata (Burm. f.) Wall. ex Nees (Acanthaceae) and have been reported to exhibit a wide spectrum of activities, including protection against oxidative stress, inflammation-mediated neurodegeneration and against cerebral ischemia [1]. However, AG shows low bioavailability and high chemical and metabolic instability. Moreover, up to now, there is no experimental evidence of AG crossing the blood brain barrier (BBB) in sufficient amount to achieve therapeutically relevant concentrations in the brain. To overcome these drawbacks the aim of this study was the preparation of solid lipid nanoparticles (SLNs) for brain delivery of AG. AG-SLNs have been developed using Compritol 888 ATO as solid lipid and Brij 78 as surfactant by emulsion/evaporation/solidifying method [2]. SLNs showed spherical shape and mean diameter below 300nm with narrow size dispersion (PdI lower than 0.2) and z-potential around -35 mV; encapsulation percentage was 92% and exhibited in vitro AG controlled and sustained release profile for at least 72h. In vitro transport studies using artificial membranes (Parallel Artificial Membrane Permeability Assay) and hCMEC/D3 cells revealed that SLNs were successful in enhancing the permeation of AG. Fluorescent-SLNs were also developed using fluorescein isothiocyanate for in vivo test in healthy rats. SLNs were administrated by intravenous route and were detected in the brain parenchyma twenty-four and seventy-two hours after administration, by confirming their ability to overcome the BBB.