Lactoferrin Coupled Lower Generation PAMAM Dendrimers for Brain Targeted Delivery of Memantine in Aluminum-Chloride-Induced Alzheimer’s Disease in Mice

Lower generation PAMAM dendrimers have immense potential of drug delivery with lesser toxicity, but these dendrimers yet need certain basic ameliorations. In this study, brain delivery potential of synthesized PAMAM-Lf (lower generation PAMAM and lactoferrin conjugate) loaded with memantine (MEM) was explored and evaluated in vitro and in vivo in the disease-induced mice model. The developed nano-scaffolds were characterized for size, zeta, and in-vitro release. Increase in the average size by 11.54±0.91 and 131.72±4.73 nm, respectively, was observed for drug-loaded PAMAM (i.e. PAMAM-MEM) and PAMAM-Lf (i.e. MEM-PAMAM-Lf), respectively. Release profile from MEM-PAMAM-Lf was slow and sustained up to 48 h. In vivo bio-distribution in Sprague-Dawley rat model revealed that brain uptake of MEM-PAMAM-Lf was significantly higher than MEM alone. The behavioral response study did not result in any significant changes. The in vivo study in AlCl3 induced Alzheimer’s (AD) animal model, observed a significant improvem...