Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route
| Autor: | Shruti S. Shikhande, Peeyush N. Goel, S. M. Patil, Amrita N. Bajaj, Darshana S. Jain, Rajani B. Athawale, Rajiv P. Gude, Preeti Raut, Abhijeet Pandey |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Nasal cavity
Erythrocytes Materials science Mucociliary clearance Drug Compounding Polyesters Cmax Antineoplastic Agents Bioengineering Nanotechnology Mucous membrane of nose Poloxamer 02 engineering and technology Pharmacology Hemolysis 030226 pharmacology & pharmacy Biomaterials 03 medical and health sciences 0302 clinical medicine Pharmacokinetics In vivo medicine Animals Humans Particle Size Rats Wistar Administration Intranasal Drug Carriers Brain Neoplasms Brain 021001 nanoscience & nanotechnology Rats Nasal Mucosa Methotrexate medicine.anatomical_structure Blood-Brain Barrier Mechanics of Materials Nanoparticles Nasal administration 0210 nano-technology Drug carrier Half-Life |
| Zdroj: | Materials Science and Engineering: C. 63:411-421 |
| ISSN: | 0928-4931 |
| DOI: | 10.1016/j.msec.2016.03.015 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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