Macrophage selective photodynamic therapy by meta-tetra(hydroxyphenyl)chlorin loaded polymeric micelles : a possible treatment for cardiovascular diseases
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ViittausWennink JWH. Liu Y. Mäkinen PI. Setaro F. de la Escosura A. Bourajjaj M. Lappalainen JP. Holappa LP. van den Dikkenberg JB. Al Fartousi M. Trohopoulos PN. Ylä-Herttuala S. Torres T. Hennink WE. van Nostrum CF. (2017). Macrophage selective photodynamic therapy by meta-tetra(hydroxyphenyl)chlorin loaded polymeric micelles : a possible treatment for cardiovascular diseases. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 107, 112-125. 10.1016/j.ejps.2017.06.038.
Selective elimination of macrophages by photodynamic therapy (PDT) is a new and promising therapeutic modality for the reduction of atherosclerotic plaques. m-Tetra(hydroxyphenyl)chlorin (mTHPC, or Temoporfin) may be suitable as photosensitizer for this application, as it is currently used in the clinic for cancer PDT. In the present study, mTHPC was encapsulated in polymeric micelles based on benzyl-poly(ε-caprolactone)-b-methoxy poly(ethylene glycol) (Ben-PCL-mPEG) using a film hydration method, with loading capacity of 17%. Because of higher lipase activity in RAW264.7 macrophages than in C166 endothelial cells, the former cells degraded the polymers faster, resulting in faster photosensitizer release and higher in vitro photocytotoxicity of mTHPC-loaded micelles in those macrophages. However, we observed release of mTHPC from the micelles in 30 min in blood plasma in vitro which explains the observed similar in vivo pharmacokinetics of the mTHPC micellar formulation and free mTHPC. Therefore, we could not translate the beneficial macrophage selectivity from in vitro to in vivo. Nevertheless, we observed accumulation of mTHPC in atherosclerotic lesions of mice aorta's which is probably the result of binding to lipoproteins upon release from the micelles. Therefore, future experiments will be dedicated to increase the stability and thus allow accumulation of intact mTHPC-loaded Ben-PCL-mPEG micelles to macrophages of atherosclerotic lesions.