Photodynamic therapy with local photosensitizer delivery inhibits experimental intimal hyperplasia.
BACKGROUND
Photodynamic therapy (PDT), the light activation of photosensitizer dyes for the production of free radicals, effectively inhibits experimental intimal hyperplasia with systemic administration of the photosensitizer. The local application of the photosensitizer directly into a vascular lesion to avoid systemic side effects and tightly control dose administration has theoretical appeal. The aim of this study was to quantify serum and arterial tissue uptake after site-specific photosensitizer delivery and, following PDT, determine its effectiveness at inhibiting intimal hyperplasia.


METHODS
The rat common carotid artery was balloon-injured, pressurized at 400 mm Hg for 2 minutes with the photosensitizer dye benzoporphyrin-derivative (BPD), and irradiated with 690 nm laser light at a fluence of 100 J/cm2. 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 intima and media and was associated with relatively high tissue, but almost no detectable serum BPD concentrations. No skin photosensitization or other systemic side effects were observed with photosensitizer administration. After 9 days, PDT-treated arteries displayed a significantly lower number of smooth muscle cells in the arterial wall than balloon-injured (P < 0.001) or saline-pressurized arteries (P < 0.0002), and no intimal hyperplasia. At 21 days, IH after PDT was significantly reduced as compared with balloon-injured (P < 0.0004), or saline-pressurized arteries (P < 0.003) with no arterial dilatation.


CONCLUSIONS
Site-specific delivery of liposomal BPD followed by PDT represents a safe method to treat arteries, and may be effectively used in vivo to inhibit the development of intimal hyperplasia.
Adili
F
F
Division of Vascular Surgery, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Statius van Eps
R G
RG
Flotte
T J
TJ
LaMuraglia
G M
GM
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004353:Drug Evaluation, Preclinical; D006965:Hyperplasia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D015552:Injections, Intralesional / Q000379:methods; D053685:Laser Therapy; D008297:Male; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011166:Porphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin