NANOSTRUCTURED LIPOSOMES FOR NOSE TO BRAIN DELIVERY OF CARMUSTINE: IN VIVO EVALUATION

Abstract

Nano sized particles are promising mediators for the administration of active compounds in the nasal and cerebral systems. However, the ability to achieve relevant therapeutic concentrations of exogenous molecules in the body is dependent mainly on the capability of nanoparticles to break down biological obstructions. In this work, nanoscale formulations conveying the minimally soluble model drug Carmustine (CS) were discussed. Box Behnken design (QbD tool) was applied to predict the interactions between the independent variable (drug-lipid ratio (X1), cholesterol (X2) and Critical Process Parameters (sonication time, X3) on the dependent variable (Entrapment efficiency (Y1), Particle size (Y2) and in vitro drug release (Y3)). The nano scale liposomal optimized Carmustine formulation (NSL-OCS) was investigated for their effect on the biopharmaceutical facets decisive for nose-to-brain delivery such as permeation across the nasal mucosa. An in vivo pharmacokinetic study was performed in Wistar albino rats via intravenous routes. Histopathologic studies support the absence of evidence of toxicity. In vitro drug dissemination studies show rapid drug release followed by extended release of CS for up to 24 hrs. The Pharmacokinetic parameters of NSLs in brain were higher in intranasal route compared to NSLs administered by intravenous route. The findings showed that the intranasal pathway can be an effective approach to administering the drug straight to the brain and improve the drug's efficacy in the brain to treat brain tumors and become a good substitute to oral medication.