Vitamin E modified polyamidoamine dendrimer for piperine delivery to alleviate Aβ induced neurotoxicity in Balb/c mice model.

In Alzheimer's disease (AD), amyloid beta (Aβ) aggregate formation and neurofibrillary tangles are major pathological hallmarks which are related to neurodegeneration in the brain. To alleviate Aβ fibrils toxicity vitamin E derivative tocopheryl polyethylene glycol succinate (TPGS) was conjugated with polyamidoamine (PAMAM) dendrimer through carbodiimide reaction to synthesize TPGS-PAMAM. This TPGS-PAMAM was employed to entrap neuroprotective agent piperine (PIP) through an anti-solvent technique to prepare PIP-TPGS-PAMAM. The dendrimer conjugate was prepared to reduce Aβ induced neurotoxicity and increase acetylcholine levels in AD mice models. The synthesis of dendrimer conjugate was characterized through proton nuclear magnetic resonance (NMR) and Trinitrobenzene sulphonic acid assay (TNBS). Physical characterization of dendrimers conjugates were done through various spectroscopic, thermal and microscopy based techniques. PIP-TPGS-PAMAM showed 43.25 nm particle size with PIP percentage encapsulation efficiency of 80.35%. Further Aβ fibril disaggregation effect of nanocarrier was evaluated using Thioflavin-T (ThT) assay and circular dichroism (CD). The neuroprotection studies for PIP-TPGS-PAMAM was evaluated against neurotoxicity induced using Aβ intracerebroventricular (ICV) injected in Balb/c mice. The group of mice administered with PIP-TPGS-PAMAM exhibited an increase in the proportion of random alternations in T-maze test and novel object recognition test (NORT) exhibited an increase in working memory cognitive functions. The biochemical and histopathological analysis revealed PIP-TPGS-PAMAM treated groups enhanced acetylcholine levels, reduced ROS and Aβ content significantly. Our findings imply that PIP-TPGS-PAMAM enhanced memory and reduced cognitive deficit in mice brain induced by Aβ toxicity.