title: Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer's disease Tg2576 mice.
abstract: The therapeutic effects of curcumin in treating Alzheimer's disease (AD) depend on the ability to penetrate the blood-brain barrier. The latest nanoparticle technology can help to improve the bioavailability of curcumin, which is affected by the final particle size and stability. We developed a stable curcumin nanoparticle formulation to test in vitro and in AD model Tg2576 mice. Flash nanoprecipitation of curcumin, polyethylene glycol-polylactic acid co-block polymer, and polyvinylpyrrolidone in a multi-inlet vortex mixer, followed by freeze drying with β-cyclodextrin, produced dry nanocurcumin with mean particle size <80 nm. Nanocurcumin powder, unformulated curcumin, or placebo was orally administered to Tg2576 mice for 3 months. Before and after treatment, memory was measured by radial arm maze and contextual fear conditioning tests. Nanocurcumin produced significantly (p=0.04) better cue memory in the contextual fear conditioning test than placebo and tendencies toward better working memory in the radial arm maze test than ordinary curcumin (p=0.14) or placebo (p=0.12). Amyloid plaque density, pharmacokinetics, and Madin-Darby canine kidney cell monolayer penetration were measured to further understand in vivo and in vitro mechanisms. Nanocurcumin produced significantly higher curcumin concentration in plasma and six times higher area under the curve and mean residence time in brain than ordinary curcumin. The P(app) of curcumin and tetrahydrocurcumin were 1.8×10(-6) and 1.6×10(-5)cm/s, respectively, for nanocurcumin. Our novel nanocurcumin formulation produced highly stabilized nanoparticles with positive treatment effects in Tg2576 mice.
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR, China.
authors.forename: Kwok Kin
authors.initials: KK
authors.lastname: Cheng
authors.forename: Chin Fung
authors.initials: CF
authors.lastname: Yeung
authors.forename: Shuk Wai
authors.initials: SW
authors.lastname: Ho
authors.forename: Shing Fung
authors.initials: SF
authors.lastname: Chow
authors.forename: Albert H L
authors.initials: AH
authors.lastname: Chow
authors.forename: Larry
authors.initials: L
authors.lastname: Baum
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D003213:Conditioning, Psychological / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004285:Dogs; D004355:Drug Stability; D005239:Fear; D005260:Female; D007773:Lactates / Q000737:chemistry; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D053758:Nanoparticles; D036103:Nanotechnology; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D010539:Permeability; D058225:Plaque, Amyloid; D011092:Polyethylene Glycols / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D007773:Lactates; D018697:Nootropic Agents; D047392:beta-Cyclodextrins; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D011205:Povidone; D003474:Curcumin