title: Photochemical tissue penetration via photosensitizer for effective drug penetration in a non-vascular tumor.
abstract: To improve the tissue penetration efficiency (PE%) of hydrophilic-drugs in non-vascular drug eluting stents (DES), we designed photochemical tissue penetration (PTP) invested DES (PTP-DES). The PTP technology was applied to the stent as a covering membrane to generate singlet oxygen. Singlet oxygen damages the epithelial layer, so the PE% of released drugs could be improved. To prepare the PTP-DES membrane, chlorin e6 (Ce6, photosensitizer) was incorporated in a gemcitabine (GEM) eluting polyurethane (PU) membrane (Ce6-GEM-PU). Ce6-GEM-PU has smooth surface that is ∼40 μm thick. The photoactivity of Ce6 was maintained for 2 weeks (in vitro GEM releasing period). In a separate cell culture system, both 1.5 folds higher PE% and an improved tumor cell growth inhibition effect were shown after light exposure. Additionally, in tissue penetration experimental system, 2 folds increased in the PE% of GEM was induced by laser exposure at 80 J/cm2. Additionally, improved PE% of hydrophilic molecules (Fluorescein and GEM) was confirmed in colon tumor bearing mice. Consequentially, tumor growth, when implanted with Ce6-GEM-PU, was effectively inhibited without significant side effects. Based on these results, we believe that the PTP-DES system has great potential for improving the therapeutic effect of conventional DES.
authors.affiliation: Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Daehong
authors.initials: D
authors.lastname: Min
authors.affiliation: Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Dooyong
authors.initials: D
authors.lastname: Jeong
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222, Banpo-daero, Seoucho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Myung Gyu
authors.initials: MG
authors.lastname: Choi
authors.affiliation: Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea. Electronic address: kna6997@catholic.ac.kr.
authors.forename: Kun
authors.initials: K
authors.lastname: Na
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000737:chemistry; D016503:Drug Delivery Systems; D019793:Fluorescein / Q000737:chemistry; D008027:Light; D008297:Male; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry; D026082:Singlet Oxygen; D013499:Surface Properties; D000093542:Gemcitabine
chemical_list: D001672:Biocompatible Materials; D017319:Photosensitizing Agents; D011140:Polyurethanes; D003841:Deoxycytidine; D026082:Singlet Oxygen; D019793:Fluorescein; D000093542:Gemcitabine
keywords: Drug eluting stent; Epithelial junction; Gemcitabine; Photochemical tissue penetration