Evaluation of temoporfin affinity to β-cyclodextrins assuming self-aggregation

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Yakavets, Ilya | Lassalle, Henri-Pierre | Yankovsky, Igor | Ingrosso, Francesca | Monari, A. | Bezdetnaya, Lina | Zorin, Vladimir

Edité par CCSD ; Elsevier -

International audience. The interaction between the potent photosensitizer meta-tetrakis(3-hydroxyphenyl)chlorin (temoporfin, mTHPC) and a series of β-cyclodextrins (β-CDs) was investigated using spectroscopic analysis and molecular dynamics simulations. The possibility of improving its poor aqueous solubility with β-CDs was estimated by measuring both equilibrium solubility and association constants. Parameters of binding isotherms revealed that mTHPC strongly interacts with β-CD derivatives, forming 1:2 inclusion complexes in aqueous solution. We demonstrated that apparent binding constants strongly depend on mTHPC concentration due to the porphyrin self-aggregation. The estimated “correct” binding constants demonstrated that completely methylated β-CD exhibits the highest affinity (K = 1.1 × 107 M−1) as compared to randomly methylated β-CD (K = 7.1 × 105 M−1) and 2-hydroxypropyl substituted β-CD (K = 1.7 × 105 M−1). In fine, our results indicate that TM-β-CD should be considered as a potent vector for mTHPC targeted delivery.

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