Photochemical tissue penetration via photosensitizer for effective drug penetration in a non-vascular tumor

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 ~40μm thick. The photoactivity of Ce6 was maintained for 2 weeks (invitro 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 80J/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.