Comparative analysis of foetal calf and human low density lipoprotein: relevance for pharmacodynamics of photosensitizers.
The effects of differences in lipoprotein content on the distribution of the novel hydrophobic photosensitizer n-butyl-3-[18-(2-butylcarbamoyl-ethyl)-3,7,12,17-tetramethyl-18,13-divinyl-22,24-dihydro-porphin-2-yl]propionamide (PP-N-3) and haematoporphyrin ester (HpE), a relatively hydrophilic photosensitizer, in human (HS) and foetal calf sera (FCS), were investigated. The binding characteristics of human and foetal calf low-density lipoprotein (LDL) were characterised using a human fibroblast line (Vag 12). The uptake into cells of HpE and PP-N-3 was also examined. A comparison of the lipoprotein content, composition and receptor-binding characteristics of foetal calf and human serum was also carried out. LDL content was measured directly using sequential ultracentrifugation to isolate LDL. In our study, we found haematoporphyrin ester to bind to human very low-density lipoprotein (VLDL), LDL and high-density lipoprotein (HDL) in the ratio 2:31:65. In the case of PP-N-3 this ratio was 56:10:33. As VLDL was not detected in foetal calf serum, only binding to LDL and HDL was observed. Using the sequential ultracentrifugation technique, foetal calf serum was found to contain LDL which in turn did bind to human LDL receptors. The uptake of PP-N-3 and HpE in the presence of low density lipoprotein from foetal calf serum (FC-LDL) was not significantly different to values observed in the presence of human serum low density lipoprotein (HS-LDL).
Haylett
A K
AK
CRC Laser Oncology Group, Paterson Institute for Cancer Research, Wilmslow Rd, Manchester M20 4BX, UK. ahaylett@picr.man.ac.uk
Moore
J V
JV
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D017323:Dihematoporphyrin Ether / Q000493:pharmacokinetics / Q000494:pharmacology*; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D011166:Porphyrins / Q000493:pharmacokinetics / Q000494:pharmacology*; D011422:Propionates / Q000493:pharmacokinetics / Q000494:pharmacology*; D011485:Protein Binding; D011973:Receptors, LDL / Q000378:metabolism*
D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D017319:Photosensitizing Agents; D011166:Porphyrins; D011422:Propionates; D011973:Receptors, LDL; C466065:n-butyl-3-(18-(2-butylcarbamoyl-ethyl)-3,7,12,17-tetramethyl-18,13-divinyl-22,24-dihydro-porphin-2-yl)propionamide; D017323:Dihematoporphyrin Ether; D002784:Cholesterol