4.7 Article

Engineering Stent Based Delivery System for Esophageal Cancer Using Docetaxel

Journal

MOLECULAR PHARMACEUTICS
Volume 12, Issue 7, Pages 2305-2317

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/mp500851u

Keywords

esophageal cancer; drug eluting stent; docetaxel; cancer chemotherapy; polymeric drug delivery system; controlled release; formulation; SAXS analysis

Funding

  1. AINSE Ltd [ALNGRS14054]
  2. NSF [DMR-0520547]

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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.

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