Preparation and characterization of water-soluble albumin-bound curcumin nanoparticles with improved antitumor activity

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Curcumin (CCM), a yellow natural polyphenol extracted from turmeric (Curcuma longa), has potent anticancer properties as has been demonstrated in various human cancer cells. However, the widespread clinical application of this efficient agent in cancer and other diseases has been limited by its poor aqueous solubility and bioavailability. In this study, we prepared novel CCM-loaded human serum albumin (HSA) nanoparticles (CCM-HSA-NPs) for intravenous administration using albumin bound technology. Field emission scanning electron microscopy (FE-SEM) and dynamic light scattering (DLS) investigation confirmed a narrow size distribution in the 130-150 nm range. Furthermore, CCM-HSA-NPs showed much greater water solubility (300-fold) than free CCM, and on storage, the biological activity of CCM-HSA-NPs was preserved with negligible activity loss. In vivo distributions and vascular endothelial cells transport studies demonstrated the superiority of CCM-HSA-NPs over CCM. Amounts of CCM in tumors after treatment with CCM-HSA-NPs were about 14 times higher at 1 h after injection than that achieved by CCM. Furthermore, vascular endothelial cell binding of CCM increased 5.5-fold, and transport of CCM across a vascular endothelial cell monolayer by Transwell testing was 7.7-fold greater for CCM-HSA-NPs than CCM. Finally, in vivo antitumor tests revealed that CCM-HSA-NPs (10 or 20 mg/kg) had a greater therapeutic effect (50% or 66% tumor growth inhibition vs. PBS-treated controls) than CCM (18% inhibition vs. controls) in tumor xenograft HCT116 models without inducing toxicity. We attribute this potent antitumor activity of CCM-HSA-NPs to enhanced water solubility, increased accumulation in tumors, and an ability to traverse vascular endothelial cell. (C) 2010 Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2011-01
Language
English
Article Type
Article
Keywords

ENDOTHELIAL-CELLS; IN-VIVO; CONTRAST AGENT; CREMOPHOR-FREE; DRUG-DELIVERY; PHASE-I; PACLITAXEL; TRANSPORT; EFFICACY; ABI-007

Citation

INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.403, no.1-2, pp.285 - 291

ISSN
0378-5173
DOI
10.1016/j.ijpharm.2010.10.041
URI
http://hdl.handle.net/10203/103693
Appears in Collection
BS-Journal Papers(저널논문)
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