CORRELATION BETWEEN SITE II-SPECIFIC HUMAN SERUM-ALBUMIN (HSA) BINDING-AFFINITY AND MURINE IN-VIVO PHOTOSENSITIZING EFFICACY OF SOME PHOTOFRIN(R) COMPONENTS

Human serum albumin (HSA) is one of the key components in human blood that may influence drug distribution. As such, it is important to know the affinity of any drug for albumin, Previously, Photofrin(R) a mixt ure of monomeric, dimeric and oligomeric porphyrins, has been subjecte d to HSA binding studies. However, due to its complex nature, binding studies on Photofrin or other hematoporphyrin derivatives with HSA are inconclusive. In this report, the binding properties of some componen ts (dimers and trimers) of Photofrin(R) and the relationship between m urine photosensitizing efficacy and those binding properties were inve stigated, The interaction of these porphyrins with HSA mas investigate d by direct ultrafiltration and fluorescent titration techniques with fluorescent probes such as dansyl-L-proline (DP), which is known to in teract selectively with site II on HSA. Porphyrins also were tested fo r antitumor activity in a mouse model following intravenous administra tion and exposure to laser light. Together, the results suggest that t he photosensitizers that were preferentially bound to site II of HSA w ere most effective at controlling muring tumor regrowth.