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

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.