Engineering Stent Based Delivery System for Esophageal Cancer Using Docetaxel.
Esophageal cancer patients are often diagnosed as "advanced" cases. These patients are subjected to palliative stenting using self-expanding metallic stents (SEMS) to maintain oral alimentation. Unfortunately, SEMS get reoccluded due to tumor growth, in and over the stent struts. To investigate potential solutions to this problem, docetaxel (DTX) delivery films were prepared using PurSil AL 20 (PUS), which can be used as a covering material for the SEMS. Drug-polymer miscibility and interactions were studied. Bilayer films were prepared by adhering the blank film to the DTX loaded film in order to maintain the unidirectional delivery to the esophagus. In vitro release and the local DTX delivery were studied using in vitro permeation experiments. It was found that DTX and PUS were physically and chemically compatible. The bilayer films exhibited sustained release (>30 days) and minimal DTX permeation through esophageal tissues in vitro. The rate-determining step for the DTX delivery was calculated. It was found that >0.9 fraction of rate control lies with the esophageal tissues, suggesting that DTX delivery can be sustained for longer periods compared to the in vitro release observed. Thus, the bilayer films can be developed as a localized sustained delivery system in combination with the stent.
†Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
Mohsin
M
Shaikh
‡Ian Wark Research Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, South Australia 5095, Australia.
Namita Roy
NR
Choudhury
§ANSTO, Locked Bag 2001, Kirrawee, New South Wales 2232, Australia.
Robert
R
Knott
†Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
Sanjay
S
Garg
D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D004947:Esophagus / Q000187:drug effects*; D011108:Polymers / Q000737:chemistry; D015607:Stents; D013552:Swine; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry*
D003692:Delayed-Action Preparations; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel
and SAXS analysis; cancer chemotherapy; controlled release; docetaxel; drug eluting stent; esophageal cancer; formulation; polymeric drug delivery system