Nose-to-brain delivery of farnesylthiosalicylic acid loaded hybrid nanoparticles in the treatment of glioblastoma

Abstract

Background: Effective treatments for gliomas are highly needed in research and clinical area in order to reach a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brain-barrier (BBB) and eliminates systemic side effects. Objective: This study evaluated the antitumor efficacy of the RAS/MAPK inhibitor, farnesylthiosalicylic acid (FTA), loaded (lipid-cationic lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN versus IV application in tumor bearing rats. Patients and Methods / Material and Methods: FTA loaded HNPs were prepared, characterized and evaluated for their anticancer activity in vitro and in vivo and a biodistribution profile in rats was investigated. Results: Rat glioma bearing rats received either no treatment, a single dose or repeated treatments of 500 μM FTA loaded HNPs (~ 163.9 nm) via IN or IV application. After both single dose, and repeated treatments of IV and IN applied FTA loaded HNPs, significant tumor reduction was achieved. The biodistribution study of the same administration routes in healthy rats showed successful brain accumulation of FTA loaded HNPs with even higher presence in the olfactory bulb after nasal application. Furthermore, a lower accumulation was observed in the kidney and liver for nasal application compared to IV application. Conclusion: Herewith, we showed the potential and safer utility of IN application of FTA loaded HNPs as a non-invasive approach in glioblastoma treatment that bypasses both systemic toxicity and the BBB limitation by a direct transport route via the olfactory bulb to the brain.