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.
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, 210023, People's Republic of China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu Province, 210028, People's Republic of China.
Xuejiao
X
Liu
Cuihua
C
Jiang
Yue
Y
Li
Wei
W
Liu
Nan
N
Yao
Meng
M
Gao
Yun
Y
Ji
Dejian
D
Huang
Zhiqi
Z
Yin
Ziping
Z
Sun
Yicheng
Y
Ni
Jian
J
Zhang
D000818:Animals; D000873:Anthracenes; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001345:Autoradiography; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D007238:Infarction; D007457:Iodine Radioisotopes; D008099:Liver / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009336:Necrosis; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D011877:Radionuclide Imaging; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014018:Tissue Distribution; D051598:Whole Body Imaging
D000873:Anthracenes; D000972:Antineoplastic Agents, Phytogenic; D007457:Iodine Radioisotopes; D014677:Pharmaceutical Vehicles; D010569:Perylene; C004965:hypericin; D004121:Dimethyl Sulfoxide
aggregation; autoradiography; distribution; drug effects; drug targeting; fluorescence spectroscopy; formulation; mononuclear phagocyte system; radiolabeling; reperfused hepatic infarction