Novel diindolylmethane derivatives based NLC formulations to improve the oral bioavailability and anticancer effects in triple negative breast cancer

Chandraiah Godugu, Ravi Doddapaneni, Stephen H. Safe, Mandip Singh

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The present study demonstrates the promising anticancer effects of novel C-substituted diindolylmethane (DIM) derivatives DIM-10 and DIM-14 in aggressive TNBC models. In vitro studies demonstrated that these compounds possess strong anticancer effects. Caco-2 permeability studies resulted in poor permeability and poor oral bioavailability was demonstrated by pharmacokinetic studies. Nano structured lipid carrier (NLC) formulations were prepared to increase the clinical acceptance of these compounds. Significant increase in oral bioavailability was observed with NLC formulations. Compared to DIM-10, DIM-10 NLC formulation showed increase in Cmax and AUC values by 4.73 and 11.19-folds, respectively. Similar pattern of increase was observed with DIM-14 NLC formulations. In dogs DIM-10 NLC formulations showed an increase of 2.65 and 2.94-fold in Cmax and AUC, respectively. The anticancer studies in MDA-MB-231 orthotopic TNBC models demonstrated significant reduction in tumor volumes in DIM-10 and DIM-14 NLC treated animals. Our studies suggest that NLC formulation of both DIM-10 and 14 is effective in TNBC models.

Original languageEnglish (US)
Pages (from-to)168-179
Number of pages12
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume108
DOIs
StatePublished - Nov 1 2016

Keywords

  • Diindolylmethane
  • Nano structured lipid carriers
  • Oral bioavailability
  • Triple negative breast cancer (TNBC)

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

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