Transport of sulfonated tetraphenylporphine by lipoproteins in the hamster.
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.
de Smidt
P C
PC
Division of Biopharmaceutics, University of Leiden, The Netherlands.
Versluis
A J
AJ
van Berkel
T J
TJ
D000818:Animals; D001692:Biological Transport; D006224:Cricetinae; D004195:Disease Models, Animal; D004337:Drug Carriers; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D011166:Porphyrins / Q000378:metabolism* / Q000493:pharmacokinetics; D011169:Portal Vein
D004337:Drug Carriers; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011166:Porphyrins; C016136:tetraphenylporphine sulfonate; C049692:tetraphenylporphine