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: Daehong Min, Dooyong Jeong, Myung Gyu Choi, Kun Na
• Journal: Biomaterials (Biomaterials) Vol. 52 Pg. 484-93 (Jun 2015) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 25818454 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Biocompatible Materials
• Photosensitizing Agents
• Polyurethanes
• Deoxycytidine
• Singlet Oxygen
• Fluorescein
• Gemcitabine

Topics

• Animals
• Biocompatible Materials (chemistry)
• Cell Line, Tumor
• Cell Survival
• Colonic Neoplasms (pathology)
• Deoxycytidine (analogs & derivatives, chemistry)
• Drug Delivery Systems
• Fluorescein (chemistry)
• Light
• Male
• Materials Testing
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Photochemotherapy
• Photosensitizing Agents (chemistry)
• Polyurethanes (chemistry)
• Singlet Oxygen
• Surface Properties
• Gemcitabine