Neuroprotective Cognitive Effects of Nose-to-brain Delivered Linagliptin Loaded Polymeric Nanosuspension in Animal Model

Abstract

Objective: Insulin resistance is a common link between diabetes mellitus (DM) and dementia. The current work emphasizes the effect of linagliptin on dementia with its neuroprotective effects, which occur directly at the neuronal level, as GLP-1 receptors are exclusively expressed in neurons. Methods: The objective of the study was to formulate linagliptin-loaded polymeric nanosuspension (LS) by nanoprecipitation method and further study their pharmaceutical, pharmacodynamics, scintigraphic, and neuroprotective effects following nose-to-brain delivery in the rat model of dementia. Results: Developed LS were spherical with z-average (250.7 nm), charge (-16.3 mV), % entrapment efficiency (95.8 ± 1.45%), and % drug loading (35.78 ± 0.19%). In vitro dissolution rate (88.56 ± 1.24%) and ex vivo permeation (81.59 ± 1.06%) of LS showed a better-sustained release profile than pure linagliptin. The spatial learning/memory in the treated group of Sprague-Dawley rats were significantly improved compared with those in the control group. Conclusion: Histopathological study of LS produced no toxicity or structural damage to the nasal mucosa. Optimum pharmaceutical characterization results improved pharmacodynamic studies/ histopathological data, and gamma-scintigraphic images proved that polymeric nanosuspensions stand out as wellappreciated approaches to deliver linagliptin more efficiently to the brain via intranasal route, thereby enhancing the neuroprotective efficacy in dementia.