- Kirchmayr Elisabeth B.Sc., master student (Elisabeth.KirchmayrATstud.sbg.ac.at)
- Koch Silke B.Sc., master student (Silke.KochATstud.sbg.ac.at)
- Verwanger Thomas Dr., assistant (Thomas.VerwangerATsbg.ac.at)
In vitro tests of new hypericin conjugates
Hypericin (hyp) is used as a powerful natural photosensitizer in photodynamic therapy (PDT) and fluorescence diagnosis (FD). After selective accumulation in targets such as tumor tissue, vessels and matrix, and activated by visible light, it is able to fluoresce (FD) and to destroy the tumor mainly via generation of reactive oxygen species. After photoactivation, molecular biological mechanisms lead to different cellular endpoints: biostimulation (increased proliferation rate), repair of the damage leading to rescue of the cells, autophagy, apoptosis and necrosis. In addition, the immune system is stimulated.
Since hyp is lipophilic, it precipitates in aqueous solutions, which hinders its cellular uptake in cell culture and its dispersion via the vascular system in i.v. applications in vivo. Several attempts have been made to render hyp more hydrophilic by coupling it to molecules which act as carriers or solubility enhancers. One of these substances is polyvinylpyrrolidone (PVP). PVP-hypericin is owned by the company Sanochemia, Vienna, and should in future serve for bladder cancer diagnosis once it has been approved. However, although PVP per se is non-toxic (biocompatible), it is non-biodegradable and is known to lead to serious health issues (including the induction of liver lysosomal vacuolation), as a direct result of its biopersistent nature. This is a particularly important safety issue when high molecular weight PVP is used in high doses and/or repeated parenteral administration, as is required when applied as a drug solubilizing agent.
Therefore, the search for biodegradable, non-toxic and stable alternatives for coupling to hypericin to improve its stability in aqueous solutions continues. The compounds are designed by Ian Teasdale in the Institute of Polymer Chemistry at the University of Linz.