Pharmacokinetics, Biodistribution and in-vivo Study of Rivastigmine Tartrate nanoparticles

Abstract

In the current study, Rivastigmine Tartrate was added to solid lipid nanoparticles (SLNs) in order to enhance its absorption in the brain through systemic circulation. The modified micro emulsion cooling technology was applied to create SLNs. In order to demonstrate the SLNs' targeting to the brain, pharmacokinetic (32–155 times) as well as pharmacodynamic (3–4 times) experiments were conducted on them. Thus, to detect the existence of SLNs in the brain, fluorescent/microscopy CLSM, biodistribution, and gamma scintigraphy approaches were investigated. Blood was taken from rats 1 hour after SLNs and rivastigmine tartrate administration, and then the rats were euthanized and their harvested brains were frozen at -80°C. Under a fluorescent/confocal microscope, the obtained plasma and brain cryosections were examined for fluorescence. A biodistribution research was performed on Balb/c mice after oral and intravenous injection of rivastigmine tartrate and 99mTc-labeled SLNs, and % radioactivity/g organ was determined. Gamma scintigraphs of the New Zealand rabbits after receiving comparable treatments were then carried out. Yellow fluorescent particles seen in plasma and the brain suggested that SLNs were successfully delivered through the gut wall and the BBB. The AUC oral values for SLNs were 8.135 times higher than for rivastigmine tartrate, indicating that the former had a longer circulation. Blood AUC i.v. SLNs and rivastigmine tartrate have a ratio of ≤1, but the ratio in the brain suggests that SLNs preferentially distribute 30 times more widely there, validating their direct delivery.