title: In Vitro and In Vivo Assessment of Docetaxel Formulation Developed for Esophageal Stents.
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.
authors.affiliation: Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia.
authors.forename: Mohsin
authors.initials: M
authors.lastname: Shaikh
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Guo
authors.affiliation: Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia.
authors.forename: Yunmei
authors.initials: Y
authors.lastname: Song
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Faculty of Health, Centre for Molecular and Medical Research, Deakin University, Pigdons Road, Waurn Ponds, Geelong, Victoria, 3216, Australia.
authors.forename: Jagat Rakesh
authors.initials: JR
authors.lastname: Kanwar
authors.affiliation: Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia. Sanjay.garg@unisa.edu.au.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Garg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077143:Docetaxel; D004947:Esophagus / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015607:Stents; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel
keywords: docetaxel; drug-eluting stent; esophageal cancer; esophageal stent; self-expanding metal stents