Combination therapy using aspirin-enhanced photodynamic selective drug delivery.
In photodynamic therapy (PDT), excitation of a drug by light leads to a cascade of biochemical processes that can cause closure of blood vessels. It has been observed clinically that significant short-term leakage from the irradiated vasculature can occur prior to vessel closure and blood flow stasis. In this paper we demonstrate in a chicken embryo model that this leakage can be significantly enhanced by the presence of the cyclo-oxygenase inhibitor, aspirin. We also observe that following this aspirin-enhanced leakage, blood vessels close as effectively as after PDT in the absence of aspirin. Consequently we propose that this PDT-induced aspirin-enhanced leakage can be used to locally deliver a drug for combination therapy. This is then demonstrated in the chicken embryo using Visudyne as a PDT agent in combination with aspirin and fluorescein isothiocyanate dextran 10 kDa as leakage indicator. The latter represents a hypothetical drug to be delivered in various kinds of combination therapy. Two examples of this procedure would be the photodynamic treatment of choroidal neovasculature associated with exudative age-related macular degeneracy (AMD) where local delivery of an anti-angiogenic or an anti-inflammatory drug has been shown to be effective, or PDT of cancer where local dosing of a chemotherapeutic drug may well increase the treatment efficacy.
Debefve
E
E
Ecole Polytechnique Fédérale de Lausanne (EPFL) Laboratory of Photomedicine, CH-1015 Lausanne, Switzerland.
Pegaz
B
B
Ballini
J-P
JP
Konan
Y N
YN
van den Bergh
H
H
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects*; D002642:Chick Embryo; D003131:Combined Modality Therapy; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016503:Drug Delivery Systems; D005451:Fluorescein Angiography; D006493:Heparin / Q000494:pharmacology; D008268:Macular Degeneration / Q000188:drug therapy / Q000628:therapy; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D000077362:Verteporfin
D016861:Cyclooxygenase Inhibitors; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D006493:Heparin; D001241:Aspirin