Hypericin is a potent agent in the
photodynamic therapy of
cancers and accumulates to a large extent in
tumor tissue. To better understand the impact of
hypericin aggregates present in the delivery vehicle on the biodistribution of the compound, we compared the in vivo tissue accumulation after administering
hypericin suspended as coarse aggregates in
phosphate-buffered saline, with the biodistribution found after injection of a
solution of
hypericin in a mixture of
DMSO,
polyethylene glycol and water. When administered as coarse aggregates,
hypericin showed a pronounced uptake in liver, spleen and lung and a slow body clearance with a complete decline in
tumor/normal tissue ratios (far less than 1). In contrast, delivery of
hypericin as a
solution resulted in dramatically improved
tumor to normal tissue ratios and a relatively fast elimination from the body. To elucidate the exact localization of
hypericin in both conditions, a fluorescence microscopy study was performed on sections of spleen, liver, lung and
tumor tissue. At 24 h after injection, fluorescence in spleen, liver and lung was faint and homogeneous for dissolved
hypericin, whereas bright fluorescent spots covering the entire tissue sections were found when coarse aggregates were injected. We found that aggregates get trapped within these tissues, followed by a gradual monomerization. A direct involvement of monocytes and macrophages, however, could not be demonstrated. In conclusion, it is of critical importance that the delivery vehicle prevents extensive aggregation of
hypericin before injection and assures an efficient transfer to serum
lipoproteins upon injection. These results may also be extended to radiolabeled derivatives and other lipophilic
photosensitizers, such as
porphyrins, phthalocyanines, naphthalocyanines and chlorines, with similar aggregation properties.