Engineering Stent Based Delivery System for Esophageal Cancer Using Docetaxel

Area of Science:

• Biomaterials Science
• Oncology
• Drug Delivery Systems

Background:

• Advanced esophageal cancer often necessitates palliative stenting with self-expanding metallic stents (SEMS).
• Tumor ingrowth and overgrowth frequently cause SEMS reocclusion, hindering oral alimentation.
• Novel strategies are needed to prevent SEMS reocclusion and improve patient outcomes.

Purpose of the Study:

• To develop and evaluate docetaxel (DTX) delivery films using PurSil AL 20 (PUS) as a potential covering for SEMS.
• To investigate the compatibility and drug release characteristics of DTX-loaded PUS films.
• To assess the potential for sustained local drug delivery to mitigate SEMS reocclusion.

Main Methods:

• Preparation of bilayer films: a blank PUS film adhered to a DTX-loaded PUS film for unidirectional delivery.
• Assessment of drug-polymer miscibility and chemical interactions between DTX and PUS.
• In vitro release studies and in vitro permeation experiments using esophageal tissue models.
• Calculation of the rate-determining step for DTX delivery.

Main Results:

• DTX and PUS demonstrated excellent physical and chemical compatibility.
• The bilayer films exhibited sustained DTX release exceeding 30 days in vitro.
• Minimal DTX permeation through esophageal tissues was observed in vitro.
• Esophageal tissue was identified as the rate-determining factor for DTX delivery (>0.9 fraction of rate control).

Conclusions:

• Bilayer DTX-loaded PUS films are compatible and provide sustained drug release.
• The PUS films show potential for prolonged localized DTX delivery, exceeding initial in vitro release rates.
• These films represent a promising localized, sustained delivery system for combination therapy with SEMS in esophageal cancer.