Hematoporphyrin is being used as a photosensitizer in photodynamic therapy of tumors, as well as of other clinical cases. Many classes of tetrapyrroles, including hematoporphyrin, are partitioning quite easily into the external cytoplasmic membrane as the mechanism of cellular uptake. Several chemical and physical parameters of the membrane were studied for their effect on the extent of porphyrins' partitioning. In this manuscript we report, for the first time, a quantitative analysis of the effect of the membrane's surface electric potential on the partitioning. We prepared liposomes, as membrane models, composed on zwitterionic DMPC lipid, as well as DMPC liposomes that contain a small, varying fraction of negatively charged DMPS and positively charged DOTAP. We found that indeed the surface potential had a very strong effect on the binding constant of HP, which is negatively charged at the physiological pH that was used. The trend in the apparent binding constant can be formulated and fitted with the Gouy-Chapman model of surface potential. We found that the average concentration of HP within the aqueous shell that has a thickness of the Debye layer around the liposome is determining the extent of binding in the law of mass action.
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