Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting

The rivastigmine (RHT) loaded chitosan nanoparticles (CS-RHT NPs) were prepared by ionic gelation method to improve the bioavailability and enhance the uptake of RHT to the brain via intranasal (in.) delivery. CS-RHT NPs were characterized for particles size, particle size distribution (PDI), encapsulation efficiency, zeta potential and in vitro release study. Nose-to-brain delivery of placebo nanoparticles (CS-NPs) was investigated by confocal laser scanning microscopy technique using rhodamine-123 as a marker. The brain/blood ratio of RHT for different formulations were 0.235, 0.790 and 1.712 of RHT (iv.). RHT (i.n.), and CS-RHT NPs (i.n.) respectively at 30 min are indicative of direct nose to brain transport bypassing the BBB. The brain concentration achieved from i.n. administration of CS-NPs (966 +/- 20.66 ng ml(-1); t(max) 60 min) was significantly higher than those achieved after i.v. administration of RHT sol (387 +/- 29.51 ng ml(-1); t(max) 30 min), and in. administration of RHT solution (508.66 +/- 22.50 ng ml(-1): t(max) 60 min). The higher drug transport efficiency (355 +/- 13.52%) and direct transport percentage (71.80 +/- 6.71%) were found with CS-RHT NPs as compared to other formulation. These results suggest that CS-RHT NPs have better brain targeting efficiency and are a promising approach for i.n, delivery of RHT for the treatment and prevention of Alzheimer's disease (AD). (C) 2012 Elsevier B.V. All rights reserved.