Ursolic acid loaded intra nasal nano lipid vesicles for brain tumour: Formulation, optimization, in-vivo brain/plasma distribution study and histopathological assessment

摘要

The aim was to formulate an optimized ursolic acid (UA) loaded lipid vesicle using formulation by design approach (FbD) for improving the drug targeting by nasal route for brain tumor. Three factors were evaluated at three different levels using anethole (terpene) (A), ethanol (B) and phospholipid90 G (C) as independent variables and their individual and combined effects were observed for PDI (Y-1), vesicle size (Y-2) and encapsulation efficiency (Y-3) to select an optimal system (UALVopt). The optimized formulation was further converted into gel and evaluated for drug release, nasal permeation study, brain/plasma uptake and histopathology study. The UALVopt formulation containing anethole as terpene (1% as A), ethanol (2.6% as B) and phospholipid90 G (8.8 mg as C) showed low PDI (0.212), vesicle size (115.56 nm) and high entrapment efficiency (76.42%). The invitro drug release and ex-vivo permeation study results revealed prolonged drug release and permeation. The brain/blood ratio for UALVGopt remained significantly higher at all the time points with respect to UALVopt indicating higher and prolonged retention of drug at site of action. The histopathological study of the nasal mucosa and brain confirmed non-toxic nature of developed formulation. The formulation UALVGopt could serve as a better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its efficacy.