title: Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting.
abstract: The rivastigmine (RHT) loaded chitosan nanoparticles (CS-RHT NPs) were prepared by ionic gelation method to improve the bioavailability and enhance the uptake of RHT to the brain via intranasal (i.n.) delivery. CS-RHT NPs were characterized for particles size, particle size distribution (PDI), encapsulation efficiency, zeta potential and in vitro release study. Nose-to-brain delivery of placebo nanoparticles (CS-NPs) was investigated by confocal laser scanning microscopy technique using rhodamine-123 as a marker. The brain/blood ratio of RHT for different formulations were 0.235, 0.790 and 1.712 of RHT (i.v.), RHT (i.n.), and CS-RHT NPs (i.n.) respectively at 30 min are indicative of direct nose to brain transport bypassing the BBB. The brain concentration achieved from i.n. administration of CS-NPs (966 ± 20.66 ng ml(-1); t(max) 60 min) was significantly higher than those achieved after i.v. administration of RHT sol (387 ± 29.51 ngml(-1); t(max) 30 min), and i.n. administration of RHT solution (508.66 ± 22.50 ng ml(-1); t(max) 60 min). The higher drug transport efficiency (355 ± 13.52%) and direct transport percentage (71.80 ± 6.71%) were found with CS-RHT NPs as compared to other formulation. These results suggest that CS-RHT NPs have better brain targeting efficiency and are a promising approach for i.n. delivery of RHT for the treatment and prevention of Alzheimer's disease (AD).
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fazil
authors.forename: Shadab
authors.initials: S
authors.lastname: Md
authors.forename: Shadabul
authors.initials: S
authors.lastname: Haque
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.forename: Sanjula
authors.initials: S
authors.lastname: Baboota
authors.forename: Jasjeet Kaur
authors.initials: JK
authors.lastname: Sahni
authors.forename: Javed
authors.initials: J
authors.lastname: Ali
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D010539:Permeability; D048448:Phenylcarbamates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D000068836:Rivastigmine
chemical_list: D004337:Drug Carriers; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D048271:Chitosan; D000068836:Rivastigmine