Nose to brain delivery of nanostructured lipid carriers loaded with rivastigmine and nilotinib for treating Alzheimer’s disease: preparation, cell line study, and in vivo evaluation

Alzheimer's disease (AD) is a complex neurodegenerative that affects over 55 million people worldwide, a number expected to double by 2050 due to aging populations. This growing prevalence imposes immense societal and economic burdens on healthcare systems and caregivers. AD is challenging to treat with monotherapy, making combination therapy a more effective approach. This study focuses on delivering Rivastigmine tartrate (RIV), and Nilotinib hydrochloride monohydrate (NIL), to the brain to achieve synergistic effects against AD. The optimal ratio of the drug combination was determined using the combination index that was performed using the Neuro2a cells line. It was found to be 1:1, emphasizing the synergistic effect against the cell lines. So, nanostructured lipid carriers (NLCs) were loaded with RIV and NIL, both individually and in combination, developed and optimized in this study. The developed formulations were thoroughly characterized for globule size, polydispersity index (PDI), and entrapment efficiency (EE) for each drug and the combination. The globule size was > 200 nm, PDI > 0.3; EE < 85% in all the developed formulations. On performing an in vitro cell availability study it was found that developed NLCs showed a 1.3 to 1.4-fold increase in the viability of the cells. On conducting an in vivo study, the concentration in the brain following administration of different formulations was in the order of RIV-NIL-NLC > NIL-NLC > RIV-NLC > RIV-NIL SUS > NIL-SUS > RIV-SUS. There was a 3.5 to 5-fold increase in the concentration of RIV and NIL in the brain when administered as RIV-NIL-NLC. So, it can be concluded that the NLCs with combined drugs showed promising results, enhancing drug permeability through the intranasal route, therefore could be used for treating AD.