Incorporation of 3,3'-Diindolylmethane into Nanocapsules Improves Its Photostability, Radical Scavenging Capacity, and Cytotoxicity Against Glioma Cells

AAPS PharmSciTech. 2019 Jan 7;20(2):49. doi: 10.1208/s12249-018-1240-8.

Abstract

3,3'-Diindolylmethane (DIM) is a phytochemical that presents health benefits (antitumor, antioxidant, and anti-inflammatory effects). However, it is water insoluble and thermo- and photolabile, restraining its pharmaceutical applications. As a strategy to overcome such limitations, this study aimed the development and characterization of DIM-loaded nanocapsules (NCs) prepared with different compositions as well as the in vitro assessment of scavenging activity and cytotoxicity. The formulations were obtained using the interfacial deposition of preformed polymer method and were composed by Eudragit® RS100 or ethylcellulose as polymeric wall and primula or apricot oil as the core. All the formulations had adequate physicochemical characteristics: nanometric size (around 190 nm), low polydispersity index (< 0.2), pH value at acid range, high values of zeta potential, drug content, and encapsulation efficiency (~ 100%). Besides, nanoencapsulation protected DIM against UVC-induced degradation and increased the scavenging activity assessed by the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) and 1-1-diphenyl-2-picrylhydrazyl methods. The developed DIM-loaded nanocapsules were further evaluated regarding the in vitro release profile and cytotoxicity against a human glioblastoma cell line (U87 cells). The results demonstrated that the nanoencapsulation promoted a sustained release of the bioactive compound (in the range of 58-78% after 84 h) in comparison to its free form (86% after 12 h), as well as provided a superior cytotoxic effect against the U87 cells in the highest concentrations. Therefore, our results suggest that nanoencapsulation could be a promising approach to overcome the DIM physicochemical limitations and potentialize its biological properties.

Keywords: antioxidant activity; antitumor; indole-3-carbinol; photodegradation; polymeric nanoparticles.

MeSH terms

  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / chemistry*
  • Anticarcinogenic Agents / metabolism
  • Cell Line, Tumor
  • Cytotoxins / administration & dosage
  • Cytotoxins / chemistry*
  • Cytotoxins / metabolism
  • Drug Stability
  • Free Radical Scavengers / administration & dosage
  • Free Radical Scavengers / chemistry*
  • Free Radical Scavengers / metabolism
  • Glioma* / metabolism
  • Humans
  • Indoles / administration & dosage
  • Indoles / chemistry*
  • Indoles / metabolism
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Particle Size
  • Photic Stimulation / adverse effects*
  • Plant Oils / administration & dosage
  • Plant Oils / chemistry
  • Plant Oils / metabolism

Substances

  • Anticarcinogenic Agents
  • Cytotoxins
  • Free Radical Scavengers
  • Indoles
  • Nanocapsules
  • Plant Oils
  • 3,3'-diindolylmethane