HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Effect of a Pluronic(®) P123 formulation on the nitric oxide-generating drug JS-K.

AbstractPURPOSE:
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 IL2Rγ (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 IL2Rγ (null) mice when compared to free JS-K-treated NOD/SCID IL2Rγ (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.
AuthorsImit Kaur, Ken M Kosak, Moises Terrazas, James N Herron, Steven E Kern, Kenneth M Boucher, Paul J Shami
JournalPharmaceutical research (Pharm Res) Vol. 32 Issue 4 Pg. 1395-406 (Apr 2015) ISSN: 1573-904X [Electronic] United States
PMID25330743 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antineoplastic Agents
  • Azo Compounds
  • Blood Proteins
  • Drug Carriers
  • Micelles
  • Nitric Oxide Donors
  • O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate
  • Piperazines
  • Prodrugs
  • pluronic block copolymer P123
  • Poloxalene
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, pharmacokinetics, therapeutic use)
  • Azo Compounds (administration & dosage, pharmacokinetics, therapeutic use)
  • Blood Proteins (metabolism)
  • Cell Survival (drug effects)
  • Drug Carriers (chemistry)
  • Drug Stability
  • HL-60 Cells
  • Humans
  • Mice, Inbred NOD
  • Mice, SCID
  • Micelles
  • Molecular Structure
  • Nitric Oxide Donors (administration & dosage, pharmacokinetics, therapeutic use)
  • Particle Size
  • Piperazines (administration & dosage, pharmacokinetics, therapeutic use)
  • Poloxalene (chemistry)
  • Prodrugs (administration & dosage, pharmacokinetics)
  • Protein Binding
  • Surface Properties
  • U937 Cells
  • Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: