Brain targeting of risperidone-loaded solid lipid nanoparticles by intranasal route.
Intranasal drug delivery is known to overcome the blood-brain barrier (BBB) for delivery of drugs to brain. The objective of this study was to prepare risperidone (RSP)-loaded solid lipid nanoparticles (RSLNs) and explore the possibility of brain targeting by nose-to-brain delivery. RSLNs were prepared by solvent emulsification-solvent evaporation method and characterized for drug content, particle size and size distribution, zeta potential, and in vitro drug-release study. The pharmacodynamic study of RSLNs, which was performed by paw test using Perspex platform, showed higher hindlimb retraction time (HRT) values as compared with RSP solution (RS) indicating the superiority of RSLNs over the RS for brain targeting. The pharmacokinetics and biodistribution studies in mice showed that brain/blood ratio 1 h post-administration of RSLNs (i.n.) was found to be 1.36 ± 0.06 (nearly 10- and 5-fold higher) as compared with 0.17 ± 0.05 for RS (i.v.) and 0.78 ± 0.07 for RSLNs (i.v.), respectively. Gamma scintigraphy imaging of mice brain following intravenous and intranasal administration confirmed the localization of drug in brain. This finding substantiates the existence of direct nose-to-brain delivery route for nanoparticles administered to the nasal cavity.
Drug Delivery Laboratory, Centre of Relevance and Excellence in NDDS, G.H. Patel Building of Pharmacy, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Vadodara, India.
Sonal
S
Patel
Sandip
S
Chavhan
Heena
H
Soni
A K
AK
Babbar
Rashi
R
Mathur
A K
AK
Mishra
Krutika
K
Sawant
D000281:Administration, Intranasal; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005260:Female; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011930:Reaction Time / Q000187:drug effects; D018967:Risperidone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D012995:Solubility; D013499:Surface Properties; D014018:Tissue Distribution
D014150:Antipsychotic Agents; D004337:Drug Carriers; D008055:Lipids; D018967:Risperidone