Shaikh Mohsin, Zhang Huihui, Wang Hongyuan, Guo Xiuli, Song Yunmei, Kanwar Jagat Rakesh, Garg Sanjay
Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia.
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, 250100, People's Republic of China.
AAPS PharmSciTech. 2017 Jan 1;18(1):130-137. doi: 10.1208/s12249-016-0501-7. Epub 2016 Feb 19.
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.
