Liposome-delivered Si(IV)-naphthalocyanine as a photodynamic sensitiser for experimental tumours: pharmacokinetic and phototherapeutic studies.
The pharmacokinetic behaviour and phototherapeutic effectiveness of bis(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 microgram g-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.
Cuomo
V
V
Department of Biology, University of Padova, Italy.
Jori
G
G
Rihter
B
B
Kenney
M E
ME
Rodgers
M A
MA
D000818:Animals; D004337:Drug Carriers; D005260:Female; D008077:Lipoproteins, LDL / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage*; D008665:Metalloporphyrins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D017646:Organosilicon Compounds; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D004337:Drug Carriers; D008077:Lipoproteins, LDL; D008081:Liposomes; D008665:Metalloporphyrins; D017646:Organosilicon Compounds; D011838:Radiation-Sensitizing Agents; C072758:bis(di-isobutyloctadecylsiloxy)silicon 2,3-naphthalocyanine