The effect of 2-hydroxypropyl-β-cyclodextrin on the excited triplet state of promazine and chlorpromazine

Chlorpromazine hydrochloride (CPZ) is a widely used anti-psychotic drug that induces skin photosensitization and photoallergy response after systematic use or topical applications. The photoallergic mechanism is still unknown. However, it has been proposed that the triplet excited state (3CPZ*) could participate in the photodamaging effects. In this work, we report the photophysical properties of the triplet excited state of CPZ and its parent derivative promazine hydrochloride (PZ) in the presence of 2-hydroxypropyl-β-cyclodextrin (HPC). Absorption measurements indicate that PZ and CPZ form an inclusion complex with HPC through a 1:1 stoichiometry. The equilibrium constant at 25 °C is (2.55 ± 0.09) × 103 M−1 and (3.27 ± 0.07) × 103 M−1 for PZ and CPZ, respectively. The CPZ and PZ triplet excited state properties changed in the presence of HPC. The triplet lifetime increases with HPC concentration that is related to the amount of drug bound. In addition, the triplet intersystem crossing quantum yield was determined to be 0.45 and 0.17 for PZ and CPZ, respectively, when more than 95% of the drug molecules are bound to HPC. Altogether, these results suggest that the microenvironment plays a crucial role in the 3CPZ* and 3PZ* properties and thus it can modulate their photosensitizing effects.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlight► We studied the effect of cyclodextrin on the triplet excited state properties of chlorpromazine and promazine hydrochlorides. ► Chloropromazine and promazine form stable complexes with 2-hydroxypropyl cyclodextrin (HPC). ► The triplet excited state of the drugs, especially chlorpromazine, changes upon complex formation with HPC. ► Our results suggest that the microenvironment plays a crucial role in the 3CPZ* and 3PZ* properties and thus it can modulate their photosensitizing effects.