Evaluation of Hypericin: Effect of Aggregation on Targeting Biodistribution

Hypericin (Hy) has shown great promise as a necrosis-avid agent in cancer imaging and therapy. Given the highly hydrophobic and π-conjugated planarity characteristics, Hy tends to form aggregates. To investigate the effect of aggregation on targeting biodistribution, nonaggregated formulation (Non-Ag), aggregated formulation with overconcentrated Hy in dimethyl sulfoxide (Ag-DMSO) solution, and aggregated formulation in water solution (Ag-water) were selected by fluorescence measurement. They were labeled with 131I and evaluated for the necrosis affinity in rat model of reperfused hepatic infarction by gamma counting and autoradiography. The radioactivity ratio of necrotic liver/normal liver was 17.1, 7.9, and 6.4 for Non-Ag, Ag-DMSO, and Ag-water, respectively. The accumulation of two aggregated formulations (Ag-DMSO and Ag-water) in organs of mononuclear phagocyte system (MPS) was 2.62 ± 0.22 and 3.96 ± 0.30 %ID/g in the lung, and 1.44 ± 0.29 and 1.51 ± 0.23 %ID/g in the spleen, respectively. The biodistribution detected by autoradiography showed the same trend as by gamma counting. In conclusion, the Non-Ag showed better targeting biodistribution and less accumulation in MPS organs than aggregated formulations of Hy. The two aggregated formulations showed significantly lower and higher accumulation in targeting organ and MPS organs, respectively. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:215-222, 2015