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 (i.n.) 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 (i.v.), 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; tmax 60 min) was significantly higher than those achieved after i.v. administration of RHT sol (387 ± 29.51 ng ml−1; tmax 30 min), and i.n. administration of RHT solution (508.66 ± 22.50 ng ml−1; tmax 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).

Graphical abstractA pharmacokinetic study in rats indicates that RHT loaded CS-NPs administered intranasally (i.n.) have higher concentration in brain as compared to RHT solution (i.n.) and (i.v.).Figure optionsDownload full-size imageDownload high-quality image (41 K)Download as PowerPoint slide