Journal: Drug Invention Today

Article Id: JPRS-CDRS-00002029
Title: Preclinical pharmacokinetics, antitumor activity and single ascending dose tolerability of GBO-006 nanosuspension, a selective polo-like kinase 2 (PLK2) inhibitor
Category: Clinical Drugs Related Study
Section: Research Article
  • Abstract
  • Audio Abstract
  • Authors
  • Pdf File
  • Citation
  • My Reference
  • Methodology
  • Abstract

    Aim: The present work was executed to develop a biocompatible parenteral formulation for pharmacokinetics, efficacy and toxicology studies of GBO-006, a highly selective polo-like kinase 2 (PLK2) inhibitor that demonstrated significant tumor regression in xenograft models on intraperitoneal alternate day dosing with the DMSO. Methods: Different technologies such as cosolvency, complexation, and micelle solubilization have been explored but failed to improve the aqueous solubility at higher concentrations. Crystalline and lipid-based nanosuspensions using different surfactants were developed and evaluated for both solubility and stability. Nanosuspensions were prepared by Ultra-Turrax homogenization followed by bead milling and microfluidics evaluated for particle size reduction and morphology. The optimized formulation was checked for pharmacokinetics, antitumor activity, and tolerability. Conclusions: Nanosuspensions prepared by bead milling were stable for more than 2 weeks and showed reduced particle size of 0.26–0.3 μ. Rat and mouse intravenous and intraperitoneal pharmacokinetic studies showed a significant improvement in Cmax, AUC and systemic clearance of the compound. We have developed a biologically compatible parenteral formulation for a first-in-class, novel anticancer agent that will be progressed toward IND enabling studies.

  • Abstract Audio

    No Audio file found

  • About the authors and Affiliations

    Author(s) Name:

    Srinivas Maddi*, Srinivas Lenkalepally, Pratima Srivastava, Duraiswamy A. Jeyaraj, Arnab Roy Chowdhury, Lakshman Rajagopalan, Jang B. Gupta

    Affiliation(s) Name:

    GVK Biosciences Pvt., Ltd. Nacharam, Hyderabad, Telangana, India

    *Corresponding author: Srinivas Maddi, DMPK - Biology Division, 28A IDA Nacharam, Hyderabad - 500076, Telangana, India.

  • View Article File in pdf format.

    Article File
  • View Article Citation Here.

    0 View More
  • How to Cite my Article.

    Author:

    Srinivas Maddi*, Srinivas Lenkalepally, Pratima Srivastava, Duraiswamy A. Jeyaraj, Arnab Roy Chowdhury, Lakshman Rajagopalan, Jang B. Gupta

    Title:Preclinical pharmacokinetics, antitumor activity and single ascending dose tolerability of GBO-006 nanosuspension, a selective polo-like kinase 2 (PLK2) inhibitor
    Journal:Drug Invention Today
    Vol(issue):10 (Jan)
    Year:2018
    Page No: (14-22)
  • Experimental Methods Keywords

    Methodology:Antitumor activity, Biodistribution, Nanosuspension, Pharmacokinetics, Polo-like kinase 2 inhibitor, Triple negative breast cancer
    Research Materials:GBO-006 (2-(1H-indol-5-ylamino)-6-(2, 4-difluorophenylsulfonyl)-8-methylpyrido [2, 3-d] pyrimidin-7(8H)-one)

Keywords

Antitumor activity Biodistribution Nanosuspension Pharmacokinetics Polo-like kinase 2 inhibitor Triple negative breast cancer

Our Services

Most Downloaded List