Preparation, characterization, in vivo biodistribution and pharmacokinetic studies of donepezil-loaded PLGA nanoparticles for brain targeting

• Published in: Drug development and industrial pharmacy Vol. 40; no. 2; p. 278
• Main Authors: Md, Shadab, Ali, Mushir, Baboota, Sanjula, Sahni, Jasjeet Kaur, Bhatnagar, Aseem, Ali, Javed
• Format: Journal Article
• Language: English
• Published: England 01.02.2014
• Subjects: Animals; Brain - drug effects; Brain - metabolism; Drug Delivery Systems - methods; Indans - administration & dosage; Indans - pharmacokinetics; Lactic Acid - administration & dosage; Lactic Acid - pharmacokinetics; Nanoparticles - administration & dosage; Nanoparticles - metabolism; Particle Size; Piperidines - administration & dosage; Piperidines - pharmacokinetics; Polyglycolic Acid - administration & dosage; Polyglycolic Acid - pharmacokinetics; Rats; Rats, Sprague-Dawley; Tissue Distribution - drug effects; Tissue Distribution - physiology
• ISSN: 1520-5762
• DOI: 10.3109/03639045.2012.758130

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. 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. 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). 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.