Adequately-Sized Nanocarriers Allow Sustained Targeted Drug Delivery to Neointimal Lesions in Rat Arteries

Ryosuke Taniguchi, Yutaka Miura, Hiroyuki Koyama, Tsukasa Chida, Yasutaka Anraku, Akihiro Kishimura, Kunihiro Shigematsu, Kazunori Kataoka, Toshiaki Watanabe

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7 Citations (Scopus)

Abstract

In atherosclerotic lesions, the endothelial barrier against the bloodstream can become compromised, resulting in the exposure of the extracellular matrix (ECM) and intimal cells beneath. In theory, this allows adequately sized nanocarriers in circulation to infiltrate into the intimal lesion intravascularly. We sought to evaluate this possibility using rat carotid arteries with induced neointima. Cy5-labeled polyethylene glycol-conjugated polyion complex (PIC) micelles and vesicles, with diameters of 40, 100, or 200 nm (PICs-40, PICs-100, and PICs-200, respectively) were intravenously administered to rats after injury to the carotid artery using a balloon catheter. High accumulation and long retention of PICs-40 in the induced neointima was confirmed by in vivo imaging, while the accumulation of PICs-100 and PICs-200 was limited, indicating that the size of nanocarriers is a crucial factor for efficient delivery. Furthermore, epirubicin-incorporated polymeric micelles with a diameter similar to that of PICs-40 showed significant curative effects in rats with induced neointima, in terms of lesion size and cell number. Specific and effective drug delivery to pre-existing neointimal lesions was demonstrated with adequate size control of the nanocarriers. We consider that this nanocarrier-based drug delivery system could be utilized for the treatment of atherosclerosis.

Original languageEnglish
Pages (from-to)2108-2116
Number of pages9
JournalMolecular pharmaceutics
Volume13
Issue number6
DOIs
Publication statusPublished - Jun 6 2016

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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    Taniguchi, R., Miura, Y., Koyama, H., Chida, T., Anraku, Y., Kishimura, A., Shigematsu, K., Kataoka, K., & Watanabe, T. (2016). Adequately-Sized Nanocarriers Allow Sustained Targeted Drug Delivery to Neointimal Lesions in Rat Arteries. Molecular pharmaceutics, 13(6), 2108-2116. https://doi.org/10.1021/acs.molpharmaceut.6b00219