Repurposing linagliptin-loaded novasomes as a neuroprotectant for Alzheimer’s disease: in-vitro characterisation, statistical optimisation and ex-vivo permeation study

Abstract

AIM: Linagliptin (LGP) has poor oral bioavailability due to P-gp efflux and first-pass metabolism. This study aimed to develop LGP-loaded novasomes (LGP-NVS) for intranasal brain delivery. METHODS: LGP-NVS were prepared via thin film hydration and optimised using a Box-Behnken design, varying cholesterol, stearic acid, and span-80 levels. Fifteen formulations were evaluated for particle size, entrapment efficiency, zeta potential, and drug release. The optimised formula underwent further surface, compatibility, permeability, and stability studies. RESULTS: The optimised formula showed high entrapment (84.22% ± 1.68%), small particle size (239.35 ± 15.20 nm), plausible zeta potential (-30.25 ± 1.23 mV), polydispersity index (0.32 ± 0.058), and controlled release (66.85 ± 2.25% after 8 h). Transmission electron microscopy demonstrated uniform size. Stability was maintained over three months. Ex-vivo permeation studies showed 1.39-fold higher permeation through camel nasal mucosa compared to drug solution. CONCLUSION: Intranasal LGP-NVS might be an auspicious therapeutic avenue for the combat of Alzheimer's disease.