Modulation of Temoporfin Distribution in Blood by β-Cyclodextrin Nanoshuttles

Abstract

Photodynamic therapy represents a more targeted and less invasive alternative cancer treatment to traditional modalities. Temoporfin, as with many photosensitizers, is given by injection into a vein, and its subsequent fate is largely determined by the binding to plasma proteins and interaction with endothelial and blood cells. Thus, it is essential to be able to control and to alter the biodistribution of temoporfin in blood. In the present study, we evaluated the effect of co-administration of temoporfin with randomly methylated β-CD (Me-β-CD) on the distribution of temoporfin in the main subpopulations of blood cells of healthy donors using absorbance spectrophotometry and flow cytometry. We showed that cell-bound temoporfin fraction in blood strongly depends on the concentration of Me-β-CD. In fact, the accumulation of temoporfin in white blood cells was more sensitive than that in red blood cells, due to the higher volume of membranous organelles in white blood cells. Finally, we demonstrated that Me-β-CD significantly increases cellular uptake of temoporfin cancer human Burkitt′s lymphoma Raji cells. The presence of Me-β-CD resulted in a spotted pattern of temoporfin distribution in the plasma membrane compartment. Our results clearly demonstrated that β-CDs derivatives provide new options to modulate temoporfin biodistribution in blood.

The Photosensitizer Temoporfin (mTHPC) – Chemical, Pre‐clinical and Clinical Developments in the Last Decade†‡

“…With mTHPP it was shown that covalently linked PS-b-cyclodextrin compounds had better PDT activity in vitro against glioblastoma cells compared to inclusions complexes (369). The affinity of temoporfin to cyclodextrin could also be influenced by methylation of the cyclodextrin carrier (129,365). Temoporfin and b-cyclodextrins have also been combined with liposomes as a second carrier to obtain 'drug-in-cyclodextrin-in-liposome' nanoparticle systems.…”

“…In some of these animal investigations with temoporfin detection via fluorescence, the window-chamber tumor model has successfully been used (288,(302)(303)(304). The detection of temoporfin by fluorescence spectroscopy methods as well as absorption spectroscopy has also proven to be a valuable or perhaps even the standard tool in pharmaceutical formulation development, allowing to follow the active substance molecule when the pharmaceutical formulation interacts with body fluids and is distributed to body compartments (129,171,221,293,365,367,392). Moreover, changes in fluorescence behavior of temoporfin and changes in its absorption spectrum can be used to characterize the immediate surroundings of the photosensitizer (366,368,393,554).…”