Correlation between photodynamic efficacy of differing porphyrins and membrane partitioning behavior

The ability of a photosensitizer to partition into membrane is determined by its structure and physical properties. Partitioning behavior can be quantitated as the partition coefficient (Kp) for a particular drug. This property may be an important determinant of cytocidal efficacy in photodynamic therapy. The Kp of five photoactive drugs--13,17-ditetraammonium protoporphyrin (PH1008), photofrin II (PII), hematoporphyrin (Hp), benzoporphyrin derivative monoacid (BPD-MA), coproporphyrin (Cp), and uroporphyrin (Up)--was determined using a simple liposome system composed of sonicated egg phosphatidylcholine single bilayer vesicles. The cytocidal efficacy of each drug was compared by determining the concentration of drug resulting in 50% maximal lysis (C50) obtained by measuring the hemoglobin absorbance at 414 nm released from lysed human red blood cells. The percentage lysis at 1 microM final drug concentration was also determined. An argon-dye laser was used to administer light of 630-nm wavelength for a total exposure of 5 J/cm2. Porphyrins with a greater tendency to partition into phosphocholine bilayer membranes demonstrated a greater lytic efficacy in the rbc system utilized. The comparison of physical properties with lytic ability may be useful in understanding the mechanism by which PDT exerts its effects and in predicting the clinical efficacy of different drugs.