LIPOSOMAL DELIVERY OF A PHOTOSENSITIZER, BENZOPORPHYRIN DERIVATIVE MONOACID RING-A (BPD), TO TUMOR-TISSUE IN A MOUSE-TUMOR MODEL

Biodistribution studies were carried out on C-14-labeled benzoporphyri n derivative monoacid ring A (BPD), which had been formulated as a uni lamellar liposome or taken from a stock solution in dimethyl sulfoxide diluted into phosphate-buffered saline immediately before intravenous injection into DBA/2 mice. By and large the general distribution of B PD to various organs and tissues was comparable for both formulations. It was noted, however, that liposomal material appeared to enter tiss ues more rapidly and to be cleared more rapidly, as demonstrated by sh orter half-lives for a number of tissues including skin, lung and fat, and generally lower levels in most tissues 24 h following administrat ion. Accumulation in tumor tissue was slightly higher with liposomal B PD, and clearance rates for this tissue were equivalent (half-lives 16 .1 h for liposomal BPD and 16.9 h for aqueous BPD). When the two prepa rations were tested in a bioassay in tumor-bearing mice, photodynamic therapy (PDT) with liposomal BPD proved to be superior to the aqueous preparation when PDT was administered 3 h following intravenous admini stration of BPD. Plasma distribution studies in vitro demonstrated tha t 91.1 +/- 0.3% of the liposomal BPD distributed to the lipoprotein fr action within the first hour of mixing, whereas only 49.1 +/- 2.6% of nonliposomal BPD was associated with lipoprotein under the same condit ions. Furthermore, while lipoprotein-associated liposomal BPD distribu ted evenly between all three types of lipoprotein (high, low and very low density), a majority of nonliposomal BPD associated with the high- density lipoprotein fraction.