Current Advances of Tubulin Inhibitors in Nanoparticle Drug Delivery and Vascular Disruption/Angiogenesis

Molecules. 2016 Nov 2;21(11):1468. doi: 10.3390/molecules21111468.

Abstract

Extensive research over the last decade has resulted in a number of highly potent tubulin polymerization inhibitors acting either as microtubule stabilizing agents (MSAs) or microtubule destabilizing agents (MDAs). These inhibitors have potent cytotoxicity against a broad spectrum of human tumor cell lines. In addition to cytotoxicity, a number of these tubulin inhibitors have exhibited abilities to inhibit formation of new blood vessels as well as disrupt existing blood vessels. Tubulin inhibitors as a vascular disrupting agents (VDAs), mainly from the MDA family, induce rapid tumor vessel occlusion and massive tumor necrosis. Thus, tubulin inhibitors have become increasingly popular in the field of tumor vasculature. However, their pharmaceutical application is halted by a number of limitations including poor solubility and toxicity. Thus, recently, there has been considerable interests in the nanoparticle drug delivery of tubulin inhibitors to circumvent those limitations. This article reviews recent advances in nanoparticle based drug delivery for tubulin inhibitors as well as their tumor vasculature disruption properties.

Keywords: angiogenesis; antimitotic; multidrug resistance; nanoparticle formulations; tubulin dynamics; tubulin inhibitors; vascular disrupting agent; β-tubulin isotypes and drug resistance.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / chemistry
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Binding Sites
  • Drug Carriers* / chemistry
  • Drug Delivery Systems*
  • Humans
  • Nanoparticles* / chemistry
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Physiologic / drug effects*
  • Protein Binding
  • Tubulin / chemistry
  • Tubulin / metabolism
  • Tubulin Modulators / administration & dosage*
  • Tubulin Modulators / chemistry

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Drug Carriers
  • Tubulin
  • Tubulin Modulators