Abstract:
Rutin-flavonoid-polyphenolic has gained attention in prevention of brain cancer. The low permeability of Rutin (RU) across the blood-brain-barrier (BBB) leads to its insufficient delivery which in turns result in low therapeutic index. Therefore, developing a novel approaches enhancing the CNS delivery of RU are required for the treatment of Cancer. The aim of this research work was to develop in Nanoemulsion (NE) loaded with RU, for CNS targeting. Rutin is a poorly water soluble anticancer drug, with oral bioavailability is about 4%. Nanoemulsion were fabricated by Spontaneous Emulsification technique. Ethyl oleate was used as oil. Tween 80 was employed as surfactant and Polyethylene glycol 400 was employed as co-surfactant. Optimised RU-NEs (F7) had particle size of 228.60 nm and % drug content of 94.77 %. Finally characterized for different parameters. Differential Scanning Calorimetry and Transmission Electron Microscopy (TEM) study revealed that RU was completely homogenies in Nanoemulsion. Then the formulation were subjected to in vitro, ex vivo and in vitro cytotoxicity using (U373MG) cell line and Histopathological studies. IC₅₀ value was obtained 9.8 µg/mL of RU-NE and it did not show any toxicity and so were safe for intranasal delivery for brain targeting. In-vitro diffusion studies revealed that RU loaded NE had a significantly higher release compared to plain drug suspension (PDS). From stability study, it was found that MDS, PDI, zeta potential and % DR was not significantly changed during the period of three months at 25±2°C and 60±5% RH. So, RU loaded Nanoemulsion for intranasal delivery are considered as promising vehicle for its targeting to CNS to treat the brain cancer. RU-NE was a dramatically enhanced anticancer and antiangiogenic activities.

Keywords: Intranasal Delivery, Nanoemulsion, Brain Targeting, Spontaneous Emulsification Technique.