Behavioral and Biochemical Implications of Dendrimeric Rivastigmine in Memory-Deficit and Alzheimer’s Induced Rodents

• Published in: ACS chemical neuroscience Vol. 10; no. 8; pp. 3789 - 3795
• Main Authors: Gothwal, Avinash, Singh, Harmanpreet, Jain, Subheet Kumar, Dutta, Ankumoni, Borah, Anupom, Gupta, Umesh
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.08.2019
• Subjects: brain delivery; dendrimers; Alzheimer’s; PAMAM
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.9b00286

Exploration of dendrimers for effective drug delivery is giving promising results. The present study was designed and performed to explore the dendrimeric (polyamidoamine-lactoferrin; PAMAM-Lf) formulations for the effective rivastigmine (RIV) delivery against the Alzheimer’s induced animal model using lactoferrin as the targeting ligand. RIV delivery through PAMAM-Lf conjugates was highly efficient in the Alzheimer’s induced animal model. PAMAM-Lf conjugates also efficiently improved behavioral responses against the chemical memory deficit animal model as well as the Alzheimer’s induced animal model, separately. Behavioral responses revealed that motor and spatial memories were significantly improved (p < 0.005) over those from RIV alone. The latency time of PAMAM-Lf-RIV was 1.3 times higher over that of the pure RIV in the rotarod protocol, while it was 2.1-fold reduced in the Morris water maze test. The study also attempted to explore the mechanistic aspect of improved efficacy through biochemical evaluation (AChE histo-enzymology), which reveals that levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were unaffected, but AChE activity was improved for all forms of RIV. Conclusively, PAMAM-Lf conjugates were able to deliver RIV effectively against the Alzheimer’s induced animal model. This was further strengthened with the positive results obtained with the behavioral studies of memory-deficit animals and disease-induced animals. The study is among the first studies which report RIV delivery against the Alzheimer’s induced animal model using PAMAM dendrimers.