LIPOSOME-DELIVERED SI(IV)-NAPHTHALOCYANINE AS A PHOTODYNAMIC SENSITIZER FOR EXPERIMENTAL-TUMORS - PHARMACOKINETIC AND PHOTOTHERAPEUTIC STUDIES

The pharmacokinetic behaviour and phototherapeutic effectiveness of 6w(di-isobutyloctadecylsil- oxy)-2, 3-naphthalocyanatosilicon (iso-BOSiNc) incorporated into dipalmitoyl-phosphatidylcholine (DPPC) liposomes have been studied in Balb/c mice bearing an MS-2 fibrosarcoma. We found that iso-BOSiNc i. v. - injected at a dose of 0. 5 mg kg-1 b. w. is preferentially transported by serum lipoproteins; in particular, the photosensitiser is associated with LDL (57. 8% of total recovery in the serum) and HDL (35. 7%) while minor amounts are associated to VLDL (2. 63%) and other serum proteins (3. 89%), Iso-BOSiNc concentrations greater than 1 µgg-1 of tissue are recovered from the tumour at 12-48 h after administration while the ratio of iso-BOSiNc concentration in tumour and peritumoral tissue is greater than 10. Upon increasing the injected dose, the additional iso-BOSiNc is almost exclusively bound by HDL, which leads to large uptake of the photosensitiser by liver and spleen. The efficiency of iso-BOSiNc as a photodynamic agent was measured upon irradiation with a different dose-rate for a total light dose of 450 J cm-2. The extent of tumour necrotic area increases as a function of the time after the end of PDT treatment and reaches a maximum level after about 24 h. Moreover, the necrotic area is linearly dependent on the irradiation dose-rate up to 100 mW cm-2. In all there is substantial evidence that iso-BOSiNc delivered in a liposomal dispersion is a highly effective photosensitizer for PDT of tumours. © Macmillan Press Ltd., 1990.