Photophysical and photobiological characteristics of liposomal forms of mTHPC

Abstract : To improve the pharmacological parameters of a second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC) several commercial liposomal formulations were designed, among them Foslip, which corresponds to mTHPC in conventional liposomes. The objective of this work was to study photophysical and photobiological characteristics of Foslip. Exposure of Foslip suspensions to small light doses (10 mJ) resulted in a substantial drop in fluorescence, which however, was restored after destruction of liposomes. We attributed this behavior to photoinduced fluorescence quenching. This effect was revealed only for high local mTHPC concentrations in lipid bilayer. The results were interpreted supposing energy migration between closely located mTHPC molecules with its subsequent dissipation by the molecules of photoproduct acting as excitation energy traps. Photoinduced fluorescence quenching together with polarization techniques and liquid chromatography was successfully applied for estimation of the redistribution rate of mTHPC molecules from the liposomes to plasma proteins and lipid membranes. Foslip liposomes were shown to be stable in human blood serum for at least 3 hours. Such increased stability was attributed to incorporation of hydrophobic photosensitiser into lipid bilayer. The processes of mTHPC redistribution after Foslip intratumoral injection in a model of breast cancer recurrence were found to be in good agreement with the results obtained from in vitro study of mTHPC redistribution from Foslip to pure DPPC liposomes. It was demonstrated that photoinduced fluorescence quenching phenomena should be taken into account while using optical techniques for studying in vivo and in vitro applications of liposomal mTHPC formulations.
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Dzmitry Kachatkou. Photophysical and photobiological characteristics of liposomal forms of mTHPC. Human health and pathology. Université Henri Poincaré - Nancy 1, 2009. English. ⟨NNT : 2009NAN10060⟩. ⟨tel-01748386⟩

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