The AAPS Journal

, Volume 15, Issue 2, pp 324–336

Highly Stabilized Curcumin Nanoparticles Tested in an In Vitro Blood–Brain Barrier Model and in Alzheimer’s Disease Tg2576 Mice

  • Kwok Kin Cheng
  • Chin Fung Yeung
  • Shuk Wai Ho
  • Shing Fung Chow
  • Albert H. L. Chow
  • Larry Baum
Research Article

DOI: 10.1208/s12248-012-9444-4

Cite this article as:
Cheng, K.K., Yeung, C.F., Ho, S.W. et al. AAPS J (2013) 15: 324. doi:10.1208/s12248-012-9444-4

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 Papp 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.

Key words

Alzheimer’s diseasebehavior testsnanocurcuminoral routepharmacokinetic

Supplementary material

12248_2012_9444_MOESM1_ESM.gif (15 kb)
Fig. S1aANCOVA modeling for number of reentry errors (S1a–c) and error entries (S1d–f) in radial arm maze tests (n = 13 for NC and control, and n = 10 for CUR). After-treatment error was described by a single regression equation: \( {{\left( {\mathrm{Errors}} \right)}_{{\mathrm{after}\,\mathrm{treatment}}}}=\mathrm{constant} + a\times {{\left( {\mathrm{Errors}} \right)}_{{\mathrm{before}\,\mathrm{treatment}}}}+b\times \mathrm{treatment}\,\mathrm{group} \). (GIF 15 kb)
12248_2012_9444_MOESM2_ESM.gif (12 kb)
Fig. S1b(GIF 11 kb)
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Fig. S1c(GIF 10 kb)
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Fig. S1d(GIF 15 kb)
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Fig. S1e(GIF 11 kb)
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Fig. S1f(GIF 10 kb)
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Fig. S2aFour fields of a brain section, stained with ThT, of Tg2576 mice treated with a control, b NC or c CUR (GIF 123 kb)
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Fig. S2b(GIF 121 kb)
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Fig. S2c(GIF 106 kb)

Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  • Kwok Kin Cheng
    • 1
  • Chin Fung Yeung
    • 1
  • Shuk Wai Ho
    • 1
  • Shing Fung Chow
    • 1
  • Albert H. L. Chow
    • 1
  • Larry Baum
    • 1
  1. 1.School of PharmacyThe Chinese University of Hong KongShatin, N.T.China