Combination therapy using aspirin-enhanced photodynamic selective drug delivery

Vascul Pharmacol. 2007 Mar;46(3):171-80. doi: 10.1016/j.vph.2006.09.006. Epub 2006 Sep 29.

Abstract

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.

MeSH terms

  • Animals
  • Aspirin / pharmacology*
  • Blood Vessels / drug effects*
  • Chick Embryo
  • Combined Modality Therapy
  • Cyclooxygenase Inhibitors / pharmacology
  • Drug Delivery Systems*
  • Fluorescein Angiography
  • Heparin / pharmacology
  • Macular Degeneration / drug therapy
  • Macular Degeneration / therapy
  • Neoplasms / drug therapy
  • Neoplasms / therapy
  • Photochemotherapy / methods*
  • Photosensitizing Agents / pharmacology
  • Porphyrins / pharmacology
  • Verteporfin

Substances

  • Cyclooxygenase Inhibitors
  • Photosensitizing Agents
  • Porphyrins
  • Verteporfin
  • Heparin
  • Aspirin