Photodynamic therapy with local photosensitizer delivery inhibits experimental intimal hyperplasia

Background: Photodynamic therapy (PDT), the light activation of photosensit izer dyes for the production of free radicals, effectively inhibits experim ental intimal hyperplasia with systemic administration of the photosensitiz er. The local application of the photosensitizer directly into a vascular l esion to avoid systemic side effects and tightly control dose administratio n has theoretical appeal. The aim of this study was to quantify serum and a rterial tissue uptake after site-specific photosensitizer delivery and, fol lowing PDT, determine its effectiveness at inhibiting intimal hyperplasia. Study Design/Materials and Methods: The rat common carotid artery was ballo on-injured, pressurized at 400 mm Hg for 2 minutes with the photosensitizer dye benzoporphyrin-derivative (BPD), and irradiated with 690 nm laser ligh t at a fluence of 100 J/cm(2). Control animals were pressurized with saline only, or received no additional treatment than balloon-injury. Results: Pressurization with BPD resulted in complete penetration of the in tima and media and was associated with relatively high tissue, but almost n o detectable serum BPD concentrations. No skin photosensitization or other systemic side effects were observed with photosensitizer administration. Af ter 9 days, PDT-treated arteries displayed a significantly lower number of smooth muscle cells in the arterial wall than balloon-injured (P < 0.001) o r saline-pressurized arteries (P < 0.0002), and no intimal hyperplasia. At 21 days, IH after PDT was significantly reduced as compared with balloon-in jured (P < 0.0004), or saline-pressurized arteries (P < 0.003) with no arte rial dilatation. Conclusions: Site-specific delivery of liposomal BPD followed by PDT repres ents a safe method to treat arteries, and may be effectively used in vivo t o inhibit the development of intimal hyperplasia. (C) 1998 Wiley-Liss, Inc.