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 an immense potential for drug delivery with lower toxicity, but these dendrimers yet need certain basic ameliorations. In this study, the brain delivery potential of the 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 mouse model. The developed nanoscaffolds were characterized for size, zeta potential and in vitro release. Increase in the average size from 11.54 ± 0.91 to 131.72 ± 4.73 nm, respectively, was observed for drug-loaded PAMAM (i.e., PAMAM-MEM) and PAMAM-Lf (i.e., MEM-PAMAM-Lf). Release profile of MEM from MEM-PAMAM-Lf was slow and sustained up to 48 h. In vivo biodistribution in the Sprague-Dawley rat model revealed that the brain uptake of MEM-PAMAM-Lf was significantly higher than that of MEM alone. The behavioral response study in the healthy rats did not result in any significant changes. The in vivo study in an AlCl