Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route.
Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors.
['Jain|Darshana S|DS|', 'Bajaj|Amrita N|AN|', 'Athawale|Rajani B|RB|', 'Shikhande|Shruti S|SS|', 'Pandey|Abhijeet|A|', 'Goel|Peeyush N|PN|', 'Gude|Rajiv P|RP|', 'Patil|Satish|S|', 'Raut|Preeti|P|']
D000281:Administration, Intranasal D000818:Animals D000970:Antineoplastic Agents D001812:Blood-Brain Barrier D001921:Brain D001932:Brain Neoplasms D004337:Drug Carriers D004339:Drug Compounding D004912:Erythrocytes D006207:Half-Life D006461:Hemolysis D006801:Humans D008727:Methotrexate D053758:Nanoparticles D009297:Nasal Mucosa D010316:Particle Size D020442:Poloxamer D011091:Polyesters D051381:Rats D017208:Rats, Wistar
Thermosensitive Brain tumors Intranasal Mucociliary clearance Poly lactic acid (PLA)