In Vitro and In Vivo Assessment of Docetaxel Formulation Developed for Esophageal Stents

AAPS PharmSciTech. 2017 Jan 1;18(1):130-137. doi: 10.1208/s12249-016-0501-7. Epub 2016 Feb 19.

Abstract

Esophageal cancer (EC) mostly affects the elderly population and is frequently diagnosed at an advanced stage. Self-expanding metal stents (SEMS) are the most popular mode of palliation, but they are associated with reocclusion caused by tumor growth. To overcome this problem, docetaxel (DTX)-loaded polyurethane formulations were prepared for stent application. The films were evaluated against the cancer cell lines, OE-19 and OE-21, and normal esophageal cell line Het-1A. The DTX and the formulations were evaluated in vitro for the cytotoxicity and in vivo in nude mice. It was found that DTX and the formulations have a weak activity against the EC cell lines and an even weaker activity against Het-1A cell line. Preliminary in vivo studies showed skin toxicity in nude mice necessitating modification of the formulation. Reevaluation in a mouse xenograft model resulted in toxicity at high dose formulations while the low dose formulation exhibited modest advantage over commercial IV formulation; however, there was no significant difference between the commercial IV and blank formulation. DTX combination with an anti-cancer agent having complementary mode of action and non-overlapping toxicity could yield better outcome in future.

Keywords: docetaxel; drug-eluting stent; esophageal cancer; esophageal stent; self-expanding metal stents.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Cell Line
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods
  • Docetaxel
  • Esophagus / drug effects*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Stents
  • Taxoids / administration & dosage*
  • Taxoids / chemistry*
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • Taxoids
  • Docetaxel