Am. Richter et al., LIPOSOMAL DELIVERY OF A PHOTOSENSITIZER, BENZOPORPHYRIN DERIVATIVE MONOACID RING-A (BPD), TO TUMOR-TISSUE IN A MOUSE-TUMOR MODEL, Photochemistry and photobiology, 57(6), 1993, pp. 1000-1006
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.