Alteration of temoporfin pharmacokinetics by β-cyclodextrin derivatives

Introduction. The use of nanoscale delivery systems is the most promising way to improve the properties of new and already existing drugs. Due to their unique structure and properties β-cyclodextrin (β-CD) derivatives can be... [ view full abstract ]

Introduction. The use of nanoscale delivery systems is the most promising way to improve the properties of new and already existing drugs. Due to their unique structure and properties β-cyclodextrin (β-CD) derivatives can be successfully used for nonpolar drug administration. Recently, in our laboratory it has been shown that β-CDs and meta-tetra(hydroxyphenyl)-chlorin (temoporfin, mTHPC) effectively form inclusion complexes [1-3]. It was demonstrated that the complexation of mTHPC with β-CDs results in a complete abolishment of mTHPC aggregation in aqueous solutions and significantly alters mTHPC distribution in vitro and in vivo. In the present study, we focused on the investigation of β-CDs influence on mTHPC pharmacokinetics in blood.

Methods. Inclusion complexes between β-CDs and mTHPC were formed using co-precipitation method. Effect of β-CDs on mTHPC interaction with blood was investigated by fluorescence spectroscopy, flow cytometry and fluorescence microscopy techniques.

Results and Discussion. Firstly, it was showed that β-CDs significantly accelerate mTHPC disaggregation in blood serum while co-administration of mTHPC with β-CDs completely abolishes photosensitizer aggregation. Secondly, β-CDs have a concentration-dependent effect on the processes of mTHPC distribution in blood. Thirdly, β-CDs increase diffusion movement of mTHPC molecules allowing to reach an equilibrium distribution much faster. Finally, flow cytometry data demonstrated that the presence of β-CDs significantly accelerate mTHPC accumulation in blood cells, especially in leukocytes. Thus, β-CDs can be successfully used to alter mTHPC behavior in the blood and these findings might have a potential relevance in the improvement of mTHPC-PDT.

Acknowledgments: This work was supported by the Institut de Cancérologie de Lorraine, French “Ligue Nationale contre le Cancer (CCIR-GE)”, Belarusian Republican Foundation for Fundamental Research (BRFFR) [grant numbers М16М-049 and М17МС-028]. We thank biolitec research GmbH (Jena, Germany) for providing us with mTHPC.

References. [1] Yankovsky, I., et al., 2016. European Journal of Pharmaceutical Sciences, 91, 172–182. [2] Yakavets, I., et al., V., 2017. Dyes and Pigments 137, 299–306. [3] Yakavets I., et al., 2017. International Journal of Pharmaceutics, 529, 568-575.