Application of computational tools for the designing of Oleuropein loaded nanostructured lipid carrier for brain targeting through nasal route.

PURPOSE: Meningitis is an inflammation of meninges encircled the brain and spinal cord. Currently it can be treated with second generation cephalosporins which were ended up with an unresolvable problem called Multi Drug Resistance (MDR). Hence, there is a need to develop a better herbal molecule to conflict the MDR. METHODS: Hot Blanching technique followed by ultra sound assisted extraction using bio-solvent aqueous glycerol was used to extract OLE from olive leaves. QbD tool was applied to predict the interactions between Critical Material Attributes (Ratio of solid Lipid X(1), Concentration of Surfactant X(2)) and Critical Process Parameters (Homogenization Time X(3)) on Critical Quality Attributes (CQA, Particle Size Y(1), Zeta Potential Y(2), and Entrapment Efficiency Y(3)). Particulate characteristics were evaluated and Invivo pharmacokinetic study was done in albino Wistar rats by IV and IN route of administration. RESULTS: Thermal studies reflect the formation of low ordered crystalline structure of lipid matrix which offers higher encapsulation of drug in NLC than physical mixture. CMA and CPP show significant effect on CQA and method operable design range was developed. Histo-pathological studies confirms that there is no signs of toxicity and in-vitro drug release studies reveals a rapid release of a drug initially followed by prolonged release of oleuropein upto 24 h. The absolute bioavailability of drug loaded NLC in brain was higher in IN route compared to NLC administered by IV route. CONCLUSIONS: In a nutshell, challenges offered by the hydrophilic OLE for brain targeting can be minimized through lipidic nature of NLC. Graphical Abstract.