Title:Intranasal Delivery of Leuprolide Acetate Chitosan Nanoparticles for
Treatment of Alzheimer’s Disease
Volume: 13
Issue: 2
Author(s): Tosha Pandya and Abhay Dharamsi*
Affiliation:
- Parul Institute of Pharmacy, Parul University, Limda, Ta.waghodia, Vadodara, Gujarat 391760, India
Keywords:
Nose to brain, leuprolide acetate, chitosan nanoparticles, in vitro study, in vivo study, Alzheimer’s disease.
Abstract:
Background: Alzheimer’s is one of the primary causes and the most prevalent form of
age-related dementia worldwide. There is an urgent surge to find an effective treatment for AD due
to its social implications on society.
Aim: Present research work aims to develop Chitosan nanoparticles of leuprolide acetate for the
treatment of Alzheimer’s disease by delivery through the intranasal route.
Methods: Chitosan nanoparticles encapsulating leuprolide acetate were prepared using the ionic gelation
method and optimized using a central composite design. The optimized nanoparticles were
evaluated by DSC study, TEM analysis, release study of the drug in vitro and ex vivo, histopathology
study, and accelerated stability study, In vivo kinetic and dynamic study.
Results: The optimized formulation exhibited particle size of 254.3 ± 10.7 nm, % EE of 85.6 ± 0.8
%, and zeta potential of +18.0 ± 0.2 mv. The release of drug from optimized nanoparticles in vitro
was in a sustained manner, with only 75.7 % drug released at 48 hours. Higher permeation of the
drug from nanoparticles (Papp =5.44 ± 0.34 x 104) was observed in the diffusion study ex vivo. Sheep
nasal toxicity and accelerated stability study proved the intranasal safety and stability of the developed
formulation. The in vivo drug uptake study indicated a greater brain drug concentration from
chitosan nanoparticles than from plain drug solution. The anti-Alzheimer potential was also evident
from behavioural studies and histopathology study of rat brain.
Conclusion: Thus, the chitosan nanoparticulate formulation of leuprolide acetate was found to have
great potential for Alzheimer’s disease management.