Photosensitizer loaded HSA nanoparticles. I: Preparation and photophysical properties

Photodynamic therapy (PDT) is a promising option in the treatment of cancer. Efficient photosensitizers are available but many of them have insufficient physico-chemical properties for parenteral application. We have established nanoparticles consisting of human serum albumin (HSA) as a drug carrier system for 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrine (mTHPP) and 5,10,15,20-tertrakis(m-hydroxyphenyl)chlorin (mTHPC), two well-known photosensitizers. Nanoparticle loading was performed in water/ethanol mixtures in the presence of dissolved HSA acting as solubilizer for photosensitizers. The HSA concentration was optimized to exclude precipitation in the nanoparticle suspension and to increase binding to nanoparticles. Additionally, the influence of pH and incubation time on drug adsorption was investigated. A freeze drying method was established for mTHPC loaded nanoparticles and the storage stability of the freeze dried formulation was tested. PDT related photophysical parameters of drug loaded HSA nanoparticles, especially singlet oxygen generation, are presented. Both preparations were able to generate singlet oxygen with low quantum yield. In contrast, efficient singlet oxygen generation was obtained when Jurkat cells were incubated with mTHPP and mTHPC loaded HSA nanoparticles. This indicates that the photosensitizer molecules were successfully released from the nanoparticles that were taken up by the cells. Therefore, the efficiency of HSA nanoparticles as drug carriers for photosensitizers was proven under in vitro conditions.