Effect of a $ Pluronic^{®} $ P123 Formulation on the Nitric Oxide-Generating Drug JS-K
Purpose $ O^{2} $-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] or JS-K is a nitric oxide-producing prodrug of the arylated diazeniumdiolate class with promising anti-tumor activity. JS-K has challenging solubility and stability properties. We aimed to characterize and compare $ Pluronic^{®} $ P123-formulated JS-K (P123/JS-K) with free JS-K. Methods We determined micelle size, shape, and critical micelle concentration of $ Pluronic^{®} $ P123. Efficacy was evaluated in vitro using HL-60 and U937 cells and in vivo in a xenograft in NOD/SCID IL2R$ γ^{null} $ mice using HL-60 cells. We compared JS-K and P123/JS-K stability in different media. We also compared plasma protein binding of JS-K and P123/JS-K. We determined the binding and Stern Volmer constants, and thermodynamic parameters. Results Spherical P123/JS-K micelles were smaller than blank P123. P123/JS-K formulation was more stable in buffered saline, whole blood, plasma and RPMI media as compared to free JS-K. P123 affected the protein binding properties of JS-K. In vitro it was as efficacious as JS-K alone when tested in HL-60 and U937 cells and in vivo greater tumor regression was observed for P123/JS-K treated NOD/SCID IL2R$ γ^{null} $ mice when compared to free JS-K-treated NOD/SCID IL2R$ γ^{null} $ mice. Conclusions $ Pluronic^{®} $ P123 solubilizes, stabilizes and affects the protein binding characteristics of JS-K. P123/JS-K showed more in vivo anti-tumor activity than free JS-K..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
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| Enthalten in: |
Pharmaceutical research - 32(2014), 4 vom: 18. Okt., Seite 1395-1406 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kaur, Imit [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| BKL: |
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| doi: |
10.1007/s11095-014-1542-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
SPR016576764 |
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| 520 | |a Purpose $ O^{2} $-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] or JS-K is a nitric oxide-producing prodrug of the arylated diazeniumdiolate class with promising anti-tumor activity. JS-K has challenging solubility and stability properties. We aimed to characterize and compare $ Pluronic^{®} $ P123-formulated JS-K (P123/JS-K) with free JS-K. Methods We determined micelle size, shape, and critical micelle concentration of $ Pluronic^{®} $ P123. Efficacy was evaluated in vitro using HL-60 and U937 cells and in vivo in a xenograft in NOD/SCID IL2R$ γ^{null} $ mice using HL-60 cells. We compared JS-K and P123/JS-K stability in different media. We also compared plasma protein binding of JS-K and P123/JS-K. We determined the binding and Stern Volmer constants, and thermodynamic parameters. Results Spherical P123/JS-K micelles were smaller than blank P123. P123/JS-K formulation was more stable in buffered saline, whole blood, plasma and RPMI media as compared to free JS-K. P123 affected the protein binding properties of JS-K. In vitro it was as efficacious as JS-K alone when tested in HL-60 and U937 cells and in vivo greater tumor regression was observed for P123/JS-K treated NOD/SCID IL2R$ γ^{null} $ mice when compared to free JS-K-treated NOD/SCID IL2R$ γ^{null} $ mice. Conclusions $ Pluronic^{®} $ P123 solubilizes, stabilizes and affects the protein binding characteristics of JS-K. P123/JS-K showed more in vivo anti-tumor activity than free JS-K. | ||
| 700 | 1 | |a Kosak, Ken M. |e verfasserin |4 aut | |
| 700 | 1 | |a Terrazas, Moises |e verfasserin |4 aut | |
| 700 | 1 | |a Herron, James N. |e verfasserin |4 aut | |
| 700 | 1 | |a Kern, Steven E. |e verfasserin |4 aut | |
| 700 | 1 | |a Boucher, Kenneth M. |e verfasserin |4 aut | |
| 700 | 1 | |a Shami, Paul J. |e verfasserin |4 aut | |
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