title: Preparation and characterization of CK2 inhibitor-loaded cyclodextrin nanoparticles for drug delivery.
abstract: Casein Kinase 2 (CK2) is a ubiquitous kinase protein currently targeted for the treatment of some cancers. Recently, the series of indeno[1,2-b]indoles has revealed great interest as potent and selective CK(2) ATP-competitive inhibitors. Among them, 1-amino-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (CM1) was selected for an encapsulation study in order to improve its biodisponibility. Its complexation was evaluated at the molecular scale, with a series of fluorinated or hydrocarbonated amphiphilic cyclodextrins (CDs). Then the encapsulation of CM1 within CD nanoparticles at the supramolecular level was achieved. Nanoparticles formed between CM1 and hexakis[6-deoxy-6-(3-perfluorohexylpropanethio)-2,3-di-O-methyl]-α-cyclodextrin, a fluorinated amphiphilic α-cyclodextrin, gave the best results in terms of encapsulation rate, stability and drug release. These nanospheres showed an encapsulation efficiency of 65% and a sustained release of the entrapped drug over 3h. Based on these results, encapsulation within fluorinated amphiphilic CD nanoparticles could be considered as a potential drug delivery system for indenoindole-type CK2 inhibitors, allowing better biodisponibility and offering perspectives for tumor targeting development.
authors.affiliation: Université de Lyon, Université Lyon 1, CSAp, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Bâtiment Raulin, 43 Bd du 11 novembre 1918, 69622 Villeurbanne Cedex, France. florent.perret@univ-lyon1.fr
authors.forename: Florent
authors.initials: F
authors.lastname: Perret
authors.forename: Christelle
authors.initials: C
authors.lastname: Marminon
authors.forename: Wael
authors.initials: W
authors.lastname: Zeinyeh
authors.forename: Pascal
authors.initials: P
authors.lastname: Nebois
authors.forename: Andre
authors.initials: A
authors.lastname: Bollacke
authors.forename: Joachim
authors.initials: J
authors.lastname: Jose
authors.forename: Hélène
authors.initials: H
authors.lastname: Parrot-Lopez
authors.forename: Marc
authors.initials: M
authors.lastname: Le Borgne
mesh_terms: D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004355:Drug Stability; D007192:Indenes / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D053758:Nanoparticles; D013997:Time Factors; D047391:alpha-Cyclodextrins / Q000737:chemistry*
chemical_list: C582463:1-amino-5-isopropyl-5,6,7,8-tetrahydroindeno(1,2-b)indole-9,10-dione; D003692:Delayed-Action Preparations; D007192:Indenes; D007211:Indoles; D047391:alpha-Cyclodextrins; C582462:hexakis(6-deoxy-6-(3-perfluorohexylpropanethio)-2,3-di-O-methyl)-alpha-cyclodextrin; D047390:Casein Kinase II