Oleic acid incorporated gemcitabine-eluting stents for treatment of cholangiocarcinoma

One of the major issues in cholangiocarcinoma (CC) treatment is bile duct occlusion-associated symptoms. As an alternative way of surgical excision of a CC, drug-eluting stents (DESs) have developed to treat both CC and occlusion. Gemcitabine (Gem) is effective for treatment of CC, however, it has limited applicability to use in DES because of its hydrophilic property. To solve these problems, we developed stent coating membrane (PTOA10-Gem) consisted of Gem, oleic acid (OA), and pellethane (PT). PTOA10-Gem membranes were additionally coated with PT to minimize rapid initial burst and washout of water-soluble Gem. OA was incorporated as a tissue penetration enhancer, and successfully achieved enhanced Gem penetration into cancer cell sheet (5.25-fold) and mouse skin (3- fold). Moreover, PTOA10-Gem led to dramatic decrease in tumor volume by 45% for 9 days. These findings suggest that the OA incorporated PT membrane is effective to improve a therapeutic efficacy of hydrophilic drug-eluting stents to treat CC, as well as other non-vascular cancers. [Figure not available: see fulltext.]