The alteration of temoporfin distribution in multicellular tumor spheroids by β-cyclodextrins.

Fiche publication


Date publication

août 2017

Journal

International journal of pharmaceutics

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BEZDETNAYA-BOLOTINE Lina, Dr LASSALLE Henri-Pierre


Tous les auteurs :
Yakavets I, Yankovsky I, Millard M, Lamy L, Lassalle HP, Wiehe A, Zorin V, Bezdetnaya L

Résumé

To be effective anticancer drugs must penetrate tissue efficiently, reaching all target population of cancer cells in a concentration sufficient to exert a therapeutic effect. This study aimed to investigate the ability of methyl-β-cyclodextrin (Me-β-CD) and 2-hydroxypropyl-β-cyclodextrin (Hp-β-CD) to alter the penetration and diffusion of temoporfin (mTHPC) in HT29 multicellular tumor spheroids. mTHPC had а nonhomogenous distribution only on the periphery of spheroids. The presence of β-CDs significantly altered the distribution of mTHPC consisting in the increase of both the depth of photosensitizer penetration and accumulation in HT29 spheroids. We suggest that this improvement is related to the nanoshuttle mechanism of β-CD action, when β-CDs facilitate mTHPC transportation to the cells in the inner layers of spheroids. As a result of mTHPC distribution improvement, β-CDs enhance mTHPC photosensitizing activity towards HT29 multicellular tumor spheroids. The observed effects strongly depend on the type of β-CD. Thus, varying the type of β-CD we can finely tune the possibility of using mTHPC for diagnostic (delimitation of tumor margins) or therapeutic purposes.

Mots clés

2-Hydroxypropyl-beta-cyclodextrin, Drug Carriers, chemistry, HT29 Cells, Humans, Mesoporphyrins, pharmacokinetics, Neoplasms, metabolism, Spheroids, Cellular, metabolism, beta-Cyclodextrins, chemistry

Référence

Int J Pharm. 2017 Aug 30;529(1-2):568-575