Inclusion complexation with β-cyclodextrin derivatives alters photodynamic activity and biodistribution of meta-tetra(hydroxyphenyl)chlorin.
Application of meta-tetra(hydroxyphenyl)chorin (mTHPC) one of the most effective photosensitizer (PS) in photodynamic therapy of solid tumors encounters several complications resulting from its insolubility in aqueous medium. To improve its solubility and pharmacokinetic properties, two modified β-cyclodextrins (β-CDs) methyl-β-cyclodextrin (M-β-CD) and 2-hydroxypropyl-β-cyclodextrin (Hp-β-CD) were proposed. The aim of this work was to evaluate the effect of β-CDs on mTHPC behavior at various stages of its distribution in vitro and in vivo. For this purpose, we have studied the influence of the β-CDs on mTHPC binding to the serum proteins, its accumulation, distribution and photodynamic efficiency in HT29 cells. In addition, the processes of mTHPC biodistribution in HT29 tumor bearing mice after intravenous injection of PS alone or with the β-CDs were compared. Interaction of mTHPC with studied β-CDs leads to the formation of inclusion complexes that completely abolishes its aggregation after introduction into serum. It was demonstrated that the β-CDs have a concentration-dependent effect on the process of mTHPC distribution in blood serum. At high concentrations, β-CDs can form inclusion complexes with mTHPC in the blood that can have a significant impact on PS distribution out of the vascular system in solid tissues. Besides, the β-CDs increase diffusion movement of mTHPC molecules that can significantly accelerate the delivery of PS to the targets cells and tissues. In vivo study confirms the fact that the use of β-CDs allows to modify mTHPC distribution processes in tumor bearing animals that is reflected in the decreased level of PS accumulation in skin and muscles, as well as in the increased PS accumulation in tumor. Further studies are underway to verify the optimal protocols of mTHPC/β-CD formulation for photodynamic therapy.
Laboratory of Biophysics and Biotechnology, Physics Faculty, Belarusian State University, 4 Nezavisimosti Ave, 220030 Minsk, Belarus; Centre de Recherche en Automatique de Nancy (CRAN), CNRS UMR 7039 (Centre National de la Recherche Scientifique), Université de Lorraine, Campus Sciences, Vandœuvre-lès-Nancy, France; Institut de Cancérologie de Lorraine, Research Department, Avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France.
Igor
I
Yankovsky
Centre de Recherche en Automatique de Nancy (CRAN), CNRS UMR 7039 (Centre National de la Recherche Scientifique), Université de Lorraine, Campus Sciences, Vandœuvre-lès-Nancy, France; Institut de Cancérologie de Lorraine, Research Department, Avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France.
Estelle
E
Bastien
Laboratory of Biophysics and Biotechnology, Physics Faculty, Belarusian State University, 4 Nezavisimosti Ave, 220030 Minsk, Belarus; Centre de Recherche en Automatique de Nancy (CRAN), CNRS UMR 7039 (Centre National de la Recherche Scientifique), Université de Lorraine, Campus Sciences, Vandœuvre-lès-Nancy, France; Institut de Cancérologie de Lorraine, Research Department, Avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France.
Ilya
I
Yakavets
Laboratory of Biophysics and Biotechnology, Physics Faculty, Belarusian State University, 4 Nezavisimosti Ave, 220030 Minsk, Belarus.
Ivan
I
Khludeyev
Centre de Recherche en Automatique de Nancy (CRAN), CNRS UMR 7039 (Centre National de la Recherche Scientifique), Université de Lorraine, Campus Sciences, Vandœuvre-lès-Nancy, France; Institut de Cancérologie de Lorraine, Research Department, Avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France.
Henri-Pierre
HP
Lassalle
Biolitec Research GmbH, Otto-Schott-Str. 15, 07745 Jena, Germany.
Susanna
S
Gräfe
Centre de Recherche en Automatique de Nancy (CRAN), CNRS UMR 7039 (Centre National de la Recherche Scientifique), Université de Lorraine, Campus Sciences, Vandœuvre-lès-Nancy, France; Institut de Cancérologie de Lorraine, Research Department, Avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France.
Lina
L
Bezdetnaya
Laboratory of Biophysics and Biotechnology, Physics Faculty, Belarusian State University, 4 Nezavisimosti Ave, 220030 Minsk, Belarus. Electronic address: vpzorin@mail.ru.
Vladimir
V
Zorin
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008652:Mesoporphyrins / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D012867:Skin / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology*
D001798:Blood Proteins; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C072269:temoporfin
Biodistribution; Inclusion complexation; Photodynamic therapy; Photosensitizer; mTHPC; β-Cyclodextrins