TRANSPORT OF SULFONATED TETRAPHENYLPORPHINE BY LIPOPROTEINS IN THE HAMSTER

被引:8
作者
DESMIDT, PC [1 ]
VERSLUIS, AJ [1 ]
VANBERKEL, TJC [1 ]
机构
[1] LEIDEN UNIV, SYLVIUS LABS,CTR BIOPHARMACEUT SCI, DIV BIOPHARMACEUT,POB 9503, 2312 AV LEIDEN, NETHERLANDS
关键词
D O I
10.1016/0006-2952(92)90145-9
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We have examined the transport and distribution properties of a bisulfonated tetraphenylporphine (TPPS-2A), an amphiphilic photosensitizer that spontaneously associates to lipoproteins. At different times after intravenous injection of TPPS-2A in hamsters, plasma was fractionated by density ultracentrifugation and porphyrin concentrations were measured in the different plasma (lipo)protein fractions. In order to mimic human lipoprotein composition hamsters were preinjected with 23 mg of apolipoprotein/kg human low density lipoprotein. In addition, the whole body distribution is described as detected by a novel method for the tissue quantification of TPPS-2A. At 5 min after injection into the penile vein, more than 50% of the injected dose appears to be associated with lung tissue, while only 30% is present in plasma and bound exclusively to plasma lipoproteins. After the initial phase, a more retarded decrease in plasma porphyrin concentration is observed. Between 5 min and 6 hr after administration, a redistribution of TPPS-2A from the lungs to the liver takes place. It is concluded that in the hamster, an animal model representing human lipoprotein composition, TPPS-2A is transported essentially exclusively by plasma lipoproteins. No depletion or accumulation of TPPS-2A in a particular plasma lipoprotein fraction could be observed, suggesting a continuous redistribution of the compound. The molecular skeleton of TPPS-2A may serve as a model for the development of new drugs that either have improved in vivo properties due to transport by lipoproteins or have a beneficial effect on the lipoprotein particle itself.
引用
收藏
页码:2567 / 2573
页数:7
相关论文
共 19 条
[1]   THE PLASMA DISTRIBUTION OF BENZOPORPHYRIN DERIVATIVE AND THE EFFECTS OF PLASMA-LIPOPROTEINS ON ITS BIODISTRIBUTION [J].
ALLISON, BA ;
PRITCHARD, PH ;
RICHTER, AM ;
LEVY, JG .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1990, 52 (03) :501-507
[2]   ROLE OF HIGH-DENSITY, LOW-DENSITY AND VERY LOW-DENSITY LIPOPROTEINS IN THE TRANSPORT AND TUMOR-DELIVERY OF HEMATOPORPHYRIN INVIVO [J].
BAREL, A ;
JORI, G ;
PERIN, A ;
ROMANDINI, P ;
PAGNAN, A ;
BIFFANTI, S .
CANCER LETTERS, 1986, 32 (02) :145-150
[3]   LACTOSAMINATED FAB FRAGMENTS SPECIFIC FOR LOW-DENSITY LIPOPROTEINS HEPATOCYTE TARGETING AND HYPOLIPOPROTEINEMIC ACTIVITY [J].
BERNINI, F ;
VIA, DP ;
BOCAN, TMA ;
GOTTO, AM ;
SMITH, LC .
ARTERIOSCLEROSIS, 1988, 8 (06) :825-831
[4]   INVITRO INTERACTION OF THE PHOTOACTIVE ANTICANCER PORPHYRIN DERIVATIVE PHOTOFRIN-II WITH LOW-DENSITY-LIPOPROTEIN, AND ITS DELIVERY TO CULTURED HUMAN-FIBROBLASTS [J].
CANDIDE, C ;
MORLIERE, P ;
MAZIERE, JC ;
GOLDSTEIN, S ;
SANTUS, R ;
DUBERTRET, L ;
REYFTMANN, JP ;
POLONOVSKI, J .
FEBS LETTERS, 1986, 207 (01) :133-138
[5]  
DESMIDT PC, 1990, CANCER RES, V50, P7476
[6]   ASSOCIATION OF ANTISENSE OLIGONUCLEOTIDES WITH LIPOPROTEINS PROLONGS THE PLASMA HALF-LIFE AND MODIFIES THE TISSUE DISTRIBUTION [J].
DESMIDT, PC ;
LEDOAN, T ;
DEFALCO, S ;
VANBERKEL, TJC .
NUCLEIC ACIDS RESEARCH, 1991, 19 (17) :4695-4700
[7]   INTERACTIONS OF STEROIDS WITH SERUM-LIPOPROTEINS [J].
HOBBELEN, PM ;
COERT, A ;
GEELEN, JAA ;
VANDERVIES, J .
BIOCHEMICAL PHARMACOLOGY, 1975, 24 (12) :165-172
[8]   THE DISTRIBUTION OF PORPHYRINS WITH DIFFERENT TUMOR LOCALIZING ABILITY AMONG HUMAN-PLASMA PROTEINS [J].
KONGSHAUG, M ;
MOAN, J ;
BROWN, SB .
BRITISH JOURNAL OF CANCER, 1989, 59 (02) :184-188
[9]   ROLE OF LIPOPROTEINS AND ERYTHROCYTES IN THE INVITRO BINDING AND DISTRIBUTION OF CYCLOSPORIN-A IN THE BLOOD [J].
LEMAIRE, M ;
TILLEMENT, JP .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1982, 34 (11) :715-718
[10]  
MUSSER DA, 1978, J NATL CANCER I, V61, P1397