Temozolomide loaded nano lipid based chitosan hydrogel for nose to brain delivery: Characterization, nasal absorption, histopathology and cell line study

The present study was designed to develop and optimize Temozolomide nano lipid chitosan hydrogel formulations (TMZNLCHG) to target the brain through nasal route. The formulation was developed using chitosan as a gelling agent and Vit E: gelucire 44/14 blend as lipid. The formulations were evaluated for particle size, encapsulation efficiency (%EE), drug loading (DL), morphology, drug release, nasal diffusion, cell line study, and histopathology study. The particle size, PDI, %EE, %DL, and drug release were found to be 134 nm, 0.177, 88.45% ± 4.45%, 9.12% ± 0.78%, and 84.23% ± 2.78%, respectively. The enhancement ratio was more than two folds higher than TMZCHG formulation (control) suggesting the superiority of chitosan with lipid as permeability enhancer. The microscopic image of lyophilized TMZNLCHGopt displayed the spherical and rough surface morphology. IC50 was found to be 3.34 μg/ml for TMZNLCHGopt and was 160 μg/ml for pure TMZ. Further, No structural damage was observed with TMZNLCHGopt treated nasal mucosa upon histopathological examination. Overall, the present study produces encouraging findings in the formulation of a non-invasive intranasal route for brain targeting as an alternate to other route for TMZ.