Preparation, characterization, in vivo biodistribution and pharmacokinetic studies of donepezil-loaded PLGA nanoparticles for brain targeting.
OBJECTIVE
Alzheimer's disease (AD) is a progressive neurodegenerative disorder manifested by cognitive, memory deterioration and variety of neuropsychiatric symptoms. Donepezil is a reversible cholinesterase inhibitor used for the treatment of AD. The purpose of this work is to prepare a nanoparticulate drug delivery system of donepezil using poly(lactic-co-glycolic acid) (PLGA) for sustained release and efficient brain targeting.


METHODS
PLGA nanoparticles (NPs) were prepared by the solvent emulsification diffusion-evaporation technique and characterized for particle size, particle-size distribution, zeta potential, entrapment efficiency, drug loading and interaction studies and in vivo studies using gamma scintigraphy techniques.


CONCLUSIONS
The size of drug-loaded NPs (drug polymer ratio 1:1) was found to be 89.67 ± 6.43 nm. The TEM and SEM images of the formulation suggested that particle size was within 20-100 nm and spherical in shape, smooth morphology and coating of Tween-80 on the NPs was clearly observed. The release behavior of donepezil exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous sustained release. The biodistribution studies of donepezil-loaded PLGA NPs and drug solution via intravenous route revealed higher percentage of radioactivity per gram in the brain for the nanoparticulate formulation as compared with the drug solution (p < 0.05).


CONCLUSIONS
The high concentrations of donepezil uptake in brain due to coated NPs may help in a significant improvement for treating AD. But further, more extensive clinical studies are needed to check and confirm the efficacy of the prepared drug delivery system.
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard , New Delhi , India , and.
Shadab
S
Md
Mushir
M
Ali
Sanjula
S
Baboota
Jasjeet Kaur
JK
Sahni
Aseem
A
Bhatnagar
Javed
J
Ali
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000077265:Donepezil; D016503:Drug Delivery Systems / Q000379:methods*; D007189:Indans / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019344:Lactic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D010316:Particle Size; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D007189:Indans; D010880:Piperidines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077265:Donepezil