PHOTOSENSITIZING ACTIVITY OF PEGYLATED PHEOPHORBIDE a

Photodynamic therapy (PDT) is a non-invasive therapeutic modality used in a number of diseases including psoriasis, age-related macular degeneration and cancer. It involves the systemic or topic administration of a photosensitizer, followed by irradiation with light. The activated photosensitizer converts oxygen to singlet oxygen and/or reactive oxygen species (ROS) which lead to cell death and tissue necrosis. One aim of PDT research is the discovery of new photosensitizers possessing minimal dark cytotoxicity, high photodynamic properties, improved pharmacokinetics, preferential retention in diseased instead of healthy tissues, chemical stability and a good cellular uptake (1). We recently focused our efforts on pheophorbide a (Pba), a chlorophyll derivative. Pba is characterized by a stronger absorption between 650-700 nm, in the tissue-penetrating wavelength range. For in vivo applications the capacity of the photosensitiser to reach in the diseased tissues becomes critical, in particular when a large peritoneal area is interested as occurring in carcinomatosis and sarcomatosis. To improve the pharmacokinetics of the photosensitizer we conjugated Pba to polyethylene glycol (PEG). In this work we investigated in vivo whether PEGylation improved the pharmacokinetics of the photosensitizer and activity pharmacological.