Effects of albumin binding on photocytotoxicity of extracellular photosensitization reaction using talaporfin sodium to rat myocardial cells.

BACKGROUND

We previously proposed a new treatment for tachyarrhythmia using an extracellular photosensitization reaction occurring in the interstitial space of myocardia shortly after the injection of talaporfin sodium. Using myocardial cells, we studied the photocytotoxicity of this extracellular photosensitization reaction between talaporfin sodium and albumin.

METHODS

The albumin concentrations tested spanned the physiological range found in the interstitial space (0-15 mg/ml) while the talaporfin sodium concentration were varied from 0 to 40 μg/ml. The reactions were conducted in 96-well plates. To obtain the binding ratio and the amount of energy deposited into the photosensitizer, we measured the change in the absorbance spectra of talaporfin sodium solutions containing different concentrations of albumin.

RESULTS

Photocytotoxicity to myocardial cell due to the reaction decreased when physiological concentrations of albumin were added to the reaction mix, and decreased sharply when the molar concentration ratio of albumin to talaporfin sodium was between 0.3 and 1.2. A monotonic binding ratio was obtained, ranging from 10 to 80%, at albumin concentrations of 0.1-1.0 mg/ml. We found that the lethality of the extracellular photosensitization reaction towards myocardial cells had a threshold albumin concentration, even though the energy deposited into the talaporfin sodium solution was calculated to be almost constant (4.23 ± 0.19 J/well) in the presence of 0-15 mg/ml albumin.

CONCLUSIONS

Based on the likely concentration of albumin in the interstitial space, we conclude that the photodynamic efficacy of talaporfin, under conditions used here, will markedly decrease if the albumin level exceeds 0.65 mg/ml.