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The potency of a photosensitizer is conveniently measured in vitro in terms of its EC50 (extracellular photosensitizer concentration needed to cause 50% cell kill in vitro upon illumination). The potency in vivo may likewise be defined in terms of the drug dose required to elicit an effect of a given intensity. The quest for increased potency drives medicinal chemistry to optimize molecular structures, and in PDT led to literally hundreds of new photosensitizers more potent than Photofrin® . Photosensitizers with EC50 in the sub-nanomolar range are at hand. Nevertheless, only very exceptionally more potent photosensitizers succeeded in clinical trials and reached commercialization. One of the reasons for the resilience of less potent photosensitizers is that photosensitizers in general have large “phototherapeutic” windows and the use of higher doses to compensate for lower potency is not necessarily associated with an exacerbation of adverse reactions. Although pursuing the development of more potent photosensitizer systems may seem to be futile when drug doses can be safely increased, it is shown that higher potency can be an advantage in applications where the dosage is limited, such as in topical applications.
This work distinguishes the potency of a photosensitizer from its efficacy, i.e., the maximum effect that it can reach without toxicity in the dark. The molecular properties that contribute to the potency and to the efficacy of photosensitizers are discussed with special emphasis on porphyrins, chlorins and bacteriochlorins.
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