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Simulation of Stimuli-Responsive and Stoichiometrically Controlled Release Rate of Doxorubicin from Liposomes in Tumor Interstitial Fluid

To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11095-018-2380-y Byline: Eiichi Yamamoto (1), Kenji Hyodo (1), Takuya Suzuki (1), Hiroshi Ishihara (1), Hiroshi Kikuchi (2), Masaru Kato (3,4) Keywords: Doxil.sup.[R];... Full description

Journal Title: Pharmaceutical Research 2018, Vol.35(5), pp.1-9
Main Author: Yamamoto, Eiichi
Other Authors: Hyodo, Kenji , Suzuki, Takuya , Ishihara, Hiroshi , Kikuchi, Hiroshi , Kato, Masaru
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0724-8741 ; E-ISSN: 1573-904X ; DOI: 10.1007/s11095-018-2380-y
Link: http://dx.doi.org/10.1007/s11095-018-2380-y
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recordid: springer_jour10.1007/s11095-018-2380-y
title: Simulation of Stimuli-Responsive and Stoichiometrically Controlled Release Rate of Doxorubicin from Liposomes in Tumor Interstitial Fluid
format: Article
creator:
  • Yamamoto, Eiichi
  • Hyodo, Kenji
  • Suzuki, Takuya
  • Ishihara, Hiroshi
  • Kikuchi, Hiroshi
  • Kato, Masaru
subjects:
  • Doxil
  • drug release
  • liposomes
  • tumor interstitial fluid
  • simulation
ispartof: Pharmaceutical Research, 2018, Vol.35(5), pp.1-9
description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11095-018-2380-y Byline: Eiichi Yamamoto (1), Kenji Hyodo (1), Takuya Suzuki (1), Hiroshi Ishihara (1), Hiroshi Kikuchi (2), Masaru Kato (3,4) Keywords: Doxil.sup.[R]; drug release; liposomes; tumor interstitial fluid; simulation Abstract: Purpose To simulate the stimuli-responsive and stoichiometrically controlled doxorubicin (DOX) release from liposomes in in vivo tumor interstitial fluid (TIF), the effect of ammonia concentration and pH on the DOX release from liposomes in human plasma at 37[degrees]C was quantitatively evaluated in vitro and the release rate was calculated as a function of ammonia concentration and pH. Methods Human plasma samples spiked with DOX-loaded PEGylated liposomes (PLD) or Doxil.sup.[R], containing ammonia (0.3--50 mM) at different pH values, were incubated at 37[degrees]C for 24 h. After incubation, the concentration of encapsulated DOX in the samples was determined by validated solid-phase extraction (SPE)-SPE-high performance liquid chromatography. Results Accelerated DOX release (%) from liposomes was observed as the increase of ammonia concentration and pH of the matrix, and the decrease of encapsulated DOX concentration. The release rate was expressed as a function of the ammonia concentration and pH by using Henderson-Hasselbalch equation. Conclusions The DOX release from PLD in TIF was expressed as a function ammonia concentration and pH at various DOX concentrations. Further, it was found that the DOX release from liposomes in a simulated TIF was more than 15 times higher than in normal plasma. Author Affiliation: (1) 0000 0004 1756 5390, grid.418765.9, Formulation Research, Pharmaceutical Science & Technology Core Function Unit, Eisai Product Creation Systems, Eisai Co. Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki, 300-2635, Japan (2) 0000 0004 1756 5390, grid.418765.9, Tsukuba Research Laboratories, Eisai Co. Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki, 300-2635, Japan (3) 0000 0001 2151 536X, grid.26999.3d, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan (4) 0000 0000 8864 3422, grid.410714.7, Department of Bioanalytical Chemistry, School of Pharmacy, Showa University, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, 142-8555, Japan Article History: Registration Date: 01/03/2018 Received Date: 07/11/2017 Accepted Date: 01/03/2018 Online Date:
language: eng
source:
identifier: ISSN: 0724-8741 ; E-ISSN: 1573-904X ; DOI: 10.1007/s11095-018-2380-y
fulltext: fulltext
issn:
  • 1573-904X
  • 1573904X
  • 0724-8741
  • 07248741
url: Link


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titleSimulation of Stimuli-Responsive and Stoichiometrically Controlled Release Rate of Doxorubicin from Liposomes in Tumor Interstitial Fluid
creatorYamamoto, Eiichi ; Hyodo, Kenji ; Suzuki, Takuya ; Ishihara, Hiroshi ; Kikuchi, Hiroshi ; Kato, Masaru
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descriptionTo access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11095-018-2380-y Byline: Eiichi Yamamoto (1), Kenji Hyodo (1), Takuya Suzuki (1), Hiroshi Ishihara (1), Hiroshi Kikuchi (2), Masaru Kato (3,4) Keywords: Doxil.sup.[R]; drug release; liposomes; tumor interstitial fluid; simulation Abstract: Purpose To simulate the stimuli-responsive and stoichiometrically controlled doxorubicin (DOX) release from liposomes in in vivo tumor interstitial fluid (TIF), the effect of ammonia concentration and pH on the DOX release from liposomes in human plasma at 37[degrees]C was quantitatively evaluated in vitro and the release rate was calculated as a function of ammonia concentration and pH. Methods Human plasma samples spiked with DOX-loaded PEGylated liposomes (PLD) or Doxil.sup.[R], containing ammonia (0.3--50 mM) at different pH values, were incubated at 37[degrees]C for 24 h. After incubation, the concentration of encapsulated DOX in the samples was determined by validated solid-phase extraction (SPE)-SPE-high performance liquid chromatography. Results Accelerated DOX release (%) from liposomes was observed as the increase of ammonia concentration and pH of the matrix, and the decrease of encapsulated DOX concentration. The release rate was expressed as a function of the ammonia concentration and pH by using Henderson-Hasselbalch equation. Conclusions The DOX release from PLD in TIF was expressed as a function ammonia concentration and pH at various DOX concentrations. Further, it was found that the DOX release from liposomes in a simulated TIF was more than 15 times higher than in normal plasma. Author Affiliation: (1) 0000 0004 1756 5390, grid.418765.9, Formulation Research, Pharmaceutical Science & Technology Core Function Unit, Eisai Product Creation Systems, Eisai Co. Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki, 300-2635, Japan (2) 0000 0004 1756 5390, grid.418765.9, Tsukuba Research Laboratories, Eisai Co. Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki, 300-2635, Japan (3) 0000 0001 2151 536X, grid.26999.3d, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan (4) 0000 0000 8864 3422, grid.410714.7, Department of Bioanalytical Chemistry, School of Pharmacy, Showa University, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, 142-8555, Japan Article History: Registration Date: 01/03/2018 Received Date: 07/11/2017 Accepted Date: 01/03/2018 Online Date: 19/03/2018
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