Brain targeting of Atorvastatin loaded amphiphilic PLGA-b-PEG nanoparticles.
The objective of this study was to develop polysorbate 80 coated and Atorvastatin loaded poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles and to investigate advantages of coating on nanoparticles for brain delivery of Atorvastatin. The nanoparticles were prepared by nanoprecipitation method. The effects of polymer concentration, PEG content and polysorbate 80 coating on the particle size, drug loading efficiency and release behaviour of nanoparticles were investigated. Additionally, cellular uptake and brain targeting of formulated nanoparticles were studied. Particle sizes were in the range of 30-172 nm depending on formulation parameters. Increasing the polymer concentration significantly increased the nanoparticle size. Decreasing the PEG content from 15% to 5% (w/w) in polymer composition increased the nanoparticle size from 69 to 172 nm. Both coated and uncoated polysorbate 80 nanoparticles were effectively internalised within the endothelial cells. Moreover, both types of nanoparticles were able to penetrate the blood brain barrier and reach the maximum in brain 1 h post injection. It was concluded that these nanoparticles are promising nanosystems for treatment of neurological disorders.
Department of Basic Pharmaceutical Science, Faculty of Pharmacy, Hacettepe University, 06100 Sıhhiye/Ankara-Turkey.
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D000069059:Atorvastatin; D001921:Brain / Q000378:metabolism*; D005456:Fluorescent Dyes; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D011758:Pyrroles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017550:Spectroscopy, Fourier Transform Infrared
D005456:Fluorescent Dyes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D000069059:Atorvastatin