THE PLASMA DISTRIBUTION OF BENZOPORPHYRIN DERIVATIVE and THE EFFECTS OF PLASMA LIPOPROTEINS ON ITS BIODISTRIBUTION

Abstract— The plasma distribution and biodistribution of benzoporphyrin derivative were examined. Two analogs of benzoporphyrin derivative were mixed with human plasma in vitro and recovered in the lipoprotein fractions upon separation by chromatography or ultracentrifugation. The majority of both analogs was recovered with high density lipoprotein. The effect of prebinding benzoporphyrin derivative to lipoproteins on the biodistribution of the drug in vivo was studied in tumor bearing DBA/2J mice. At 3, 8 and 24 h post‐injection, tumor and tissue samples were excised and analyzed for benzoporphyrin derivative content. Precomplexing benzoporphyrin derivative with low density lipoprotein or high density lipoprotein led to significantly (P < 0.05) greater tumor accumulation than in aqueous solution.

[1]  D. Dolphin,et al.  Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice. , 1990, Journal of photochemistry and photobiology. B, Biology.

[2]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[3]  J. Hokanson,et al.  [8] Single vertical spin density gradient ultracentrifugation , 1986 .

[4]  Julia G. Levy,et al.  Characterization Of Benzoporphyrin Derivative, A New Photosensitizer , 1989, Other Conferences.

[5]  J. Hokanson,et al.  Single vertical spin density gradient ultracentrifugation. , 1986, Methods in enzymology.

[6]  G. Jori,et al.  AN ULTRASTRUCTURAL COMPARATIVE EVALUATION OF TUMORS PHOTOSENSITIZED BY PORPHYRINS ADMINISTERED IN AQUEOUS SOLUTION, BOUND TO LIPOSOMES OR TO LIPOPROTEINS , 1988, Photochemistry and photobiology.

[7]  R. P. Noble.  Electrophoretic separation of plasma lipoproteins in agarose gel. , 1968, Journal of lipid research.

[8]  J. Frohlich,et al.  Lecithin:cholesterol acyltransferase in familial HDL deficiency (Tangier disease). , 1988, Biochimica et biophysica acta.

[9]  D. Kessel,et al.  Porphyrin-lipoprotein association as a factor in porphyrin localization. , 1986, Cancer letters.

[10]  D. Dolphin,et al.  Preliminary studies on a more effective phototoxic agent than hematoporphyrin. , 1987, Journal of the National Cancer Institute.

[11]  E. Reddi,et al.  Evidence for a major role of plasma lipoproteins as hematoporphyrin carriers in vivo. , 1984, Cancer letters.

[12]  L. Rudel,et al.  Characterization of plasma lipoproteins separated and purified by agarose-column chromatography. , 1974, The Biochemical journal.

[13]  D Kessel,et al.  In vitro PHOTOSENSITIZATION WITH A BENZOPORPHYRIN DERIVATIVE , 1989, Photochemistry and photobiology.

[14]  R. Havel,et al.  The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. , 1955, The Journal of clinical investigation.

[15]  G. Jori,et al.  Role of high-, low- and very low-density lipoproteins in the transport and tumor-delivery of hematoporphyrin in vivo. , 1986, Cancer letters.

[16]  L. Dubertret,et al.  INTERACTION OF HUMAN SERUM LOW DENSITY LIPOPROTEINS WITH PORPHYRINS: A SPECTROSCOPIC AND PHOTOCHEMICAL STUDY , 1984, Photochemistry and photobiology.

[17]  J. Kelley,et al.  Density gradient ultracentrifugation of serum lipoproteins in a swinging bucket rotor. , 1986, Methods in enzymology.