Polymeric glabrescione B nanocapsules for passive targeting of Hedgehog-dependent tumor therapy in vitro

Nanomedicine (Lond). 2017 Apr;12(7):711-728. doi: 10.2217/nnm-2016-0388. Epub 2017 Mar 21.

Abstract

Aim: With the purpose of delivering high doses of glabrescione B (GlaB) to solid tumors after systemic administration, long-circulating GlaB-loaded oil-cored polymeric nanocapsules (NC-GlaB) were formulated.

Materials & methods: Synthesis of GlaB and its encapsulation in nanocapsules (NCs) was performed. Empty and GlaB-loaded NCs were assessed for their physico-chemical properties, in vitro cytotoxicity and in vivo biodistribution.

Results: GlaB was efficiently loaded into NCs (∽90%), which were small (∽160 nm), homogeneous and stable upon storage. Further, GlaB and NC-GlaB demonstrated specific activities against the cancer stem cells. Preliminary studies in tumor-bearing mice supported the ability of NC to accumulate in pancreatic tumors.

Conclusion: This study provides early evidence that NC-GlaB has the potential to be utilized in a preclinical setting and justifies the need to perform therapeutic experiments in mice.

Keywords: Hedgehog (Hh) pathway; glabrescione B (GlaB); oil-cored polymeric nanocapsules.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacokinetics
  • Cell Line, Tumor
  • Cell Survival
  • Chromones / administration & dosage*
  • Chromones / chemical synthesis
  • Chromones / pharmacokinetics
  • Drug Carriers / chemistry*
  • Female
  • Hedgehog Proteins / metabolism*
  • Heterografts
  • Humans
  • Mice
  • Mice, SCID
  • Molecular Targeted Therapy
  • Nanocapsules / chemistry*
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / drug effects
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Surface Properties
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Chromones
  • Drug Carriers
  • Hedgehog Proteins
  • Nanocapsules
  • glabrescione B
  • Polyethylene Glycols