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A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication

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Title: A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication
Authors: Hossen, Md. Nazir Browse this author
Kajimoto, Kazuaki Browse this author →KAKEN DB
Akita, Hidetaka Browse this author →KAKEN DB
Hyodo, Mamoru Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: Nanoparticle-targeted proapoptotic peptide
Diet-induced obesity
Metabolic syndrome
Ectopic fat
Issue Date: 28-Oct-2013
Publisher: Elsevier science bv
Journal Title: Journal of controlled release
Volume: 171
Issue: 2
Start Page: 104
End Page: 112
Publisher DOI: 10.1016/j.jconrel.2013.07.013
PMID: 23871959
Abstract: Antiangiogenesis has been the focus of a new strategy for the treatment of obesity. However, little is known regarding the issue of whether targeting angiogenesis by nanoparticle-targeted therapeutic is advantageous or not in debugging the co-morbidity associated with diet-induced obesity (DIO) and the metabolic syndrome. We report herein on the positive effect of prohibitin (an adipose vascular marker)-targeted nanoparticle (PTNP) encapsulated in a proapoptotic peptide [(D)(KLAKLAK)(2), KLA] on DIO and dysfunctional adipose tissue, a major mediator of the metabolic syndrome, as evidenced by ectopic fat deposition. The systemic injection of DIO mice with a low dose of KLA-PTNP, rather than a bioconjugate composed of the same targeting peptide and KLA (Adipotide) resulted in a reduction in body weight, as evidenced by a significant decrease in serum leptin levels, in parallel with an antiobesity effect on dysfunctional adipose cells, including adipocytes and macrophages. In addition, the KLA-PTNP treatment resulted in a reduction in ectopic fat deposits in liver and muscle with the lipolytic action of elevated serum adiponectin, with no detectable hepatoxicity. Notably, drug delivery via PTNP that had accumulated in obese fat via the enhanced permeability and retention effect was enhanced by multivalent active targeting and cytoplasmic delivery into adipose endothelial cells via escaping from endosomes/lysosomes. Thus, vascular-targeted nanotherapy has the potential to contribute to the control of adipose function and ectopic fat deposition associated with obesity and the metabolic syndrome. (C) 2013 Elsevier B. V. All rights reserved.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 原島 秀吉

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