Preparation and characterization of CK2 inhibitor-loaded cyclodextrin nanoparticles for drug delivery.

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.

Design, synthesis, and in vitro evaluation of new amphiphilic cyclodextrin-based nanoparticles for the incorporation and controlled release of acyclovir.

Acyclovir possesses low solubility in water and in lipid bilayers, so that its dosage forms do not allow suitable drug levels at target sites following oral, local, or parenteral administration. In order to improve this lack of solubility, new cyclodextrin-based amphiphilic derivatives have been designed to form nanoparticles, allowing the efficient encapsulation of this hydrophobic antiviral agent. The present work first describes the synthesis and characterization of five new O-2,O-3 permethylated O-6 alkylthio- and perfluoroalkyl-propanethio-amphiphilic β-cyclodextrins.

Selectivity among two lectins: probing the effect of topology, multivalency and flexibility of "clicked" multivalent glycoclusters.

The design of multivalent glycoconjugates has been developed over the past decades to obtain high-affinity ligands for lectin receptors. While multivalency frequently increases the affinity of a ligand for its lectin through the so-called "glycoside cluster effect", the binding profiles towards different lectins have been much less investigated. We have designed a series of multivalent galactosylated glycoconjugates and studied their binding properties towards two lectins, from plant and bacterial origins, to determine their potential selectivity.

Novel nanoparticles made from amphiphilic perfluoroalkyl alpha-cyclodextrin derivatives: preparation, characterization and application to the transport of acyclovir.

The preparation of aqueous suspensions of nanoparticles of the fluorinated amphiphilic alpha-cyclodextrins hexakis[6-deoxy-6-(3-perfluoroalkylpropanethio)-2,3-di-O-methyl]-alpha-cyclodextrin and their hydrocarbon analogues was studied. The complexation of acyclovir by modified alpha-cyclodextrin, the encapsulation efficiency and release profile were measured as an assessment of the properties of such nanoparticles regarding drug delivery applications. Stable aqueous suspensions of nanoparticles were prepared using nanoprecipitation method without using surface-active agent.

Control of the regioselectivity for new fluorinated amphiphilic cyclodextrins: synthesis of di- and tetra(6-deoxy-6-alkylthio)- and 6-(perfluoroalkypropanethio)-alpha-cyclodextrin derivatives.

Twelve new di- and tetraderivatized alpha-cyclodextrin molecules having either alkylthio and perfluoroalkylpropanethio functions at the primary face have been synthesized by using the procedure of Sinay for di-O-debenzylation of perbenzylated alpha-cyclodextrins. A new strategy of protection/deprotection has been developed for introducing the lipophilic chains. The coupling reaction involves the reaction between the appropriate alpha-cyclodextin derivative, regioselectively modified at C-6 positions by a good leaving group (O-mesityl for disubstituted or iodine for tetrasubstituted derivatives), with the thioalkyl or the thioperfluoroakylpropane chains.

Sulfated and non-sulfated amphiphilic-beta-cyclodextrins: impact of their structural properties on the physicochemical properties of nanoparticles.

Purpose: The aim of this work was to study the preparation of nanospheres from amphiphilic beta-cyclodextrins formed (a) by different acylation degrees (DA) at the secondary hydroxyl face (DA=14 and 21) followed by varying (b) the sulfatation degrees (DS) at the primary hydroxyl face (DS=0, 4 and 7).

Methods: The physicochemical properties of the synthesized compounds such as molecular weights, the theoretical HLB values and the critical micellar concentration values and their surface area were presented. The nanoparticles prepared from amphiphilic beta-cyclodextrins were characterized by mean size, zeta potential and their morphology.

Synthesis and characterisation of novel nanospheres made from amphiphilic perfluoroalkylthio-beta-cyclodextrins.

This work describes the synthesis of new amphiphilic perfluorohexyl- and perfluorooctyl-propanethio-beta-cyclodextrins and the comparison of the ability of these molecules and alkyl analogue, nonanethio-beta-cyclodextrin to form nanospheres. Nanospheres were prepared using nanoprecipitation method (perfluoroalkylthio-beta-cyclodextrin in THF [0.11 x 10(-3)M], stirring rate 700rpm, addition of aqueous phase at 64 degrees C into organic phase at 50 degrees C).

Synthesis and characterisation of sulfated amphiphilic alpha-, beta- and gamma-cyclodextrins: application to the complexation of acyclovir.

The synthesis of sulfated amphiphilic alpha-, beta- and gamma-cyclodextrins was achieved according to the standard protection-deprotection procedure. The formation of inclusion complexes between the amphiphilic alpha-, beta- and gamma-cyclodextrins and an antiviral molecule, acyclovir (ACV) was investigated by UV-visible spectroscopy (UV-Vis) and electrospray ionisation mass spectrometry (ESIMS). UV-Vis spectroscopy allowed determination of the stoichiometry and stability constants of complexes, whereas ESIMS, a soft ionisation technique, allowed the detection of the inclusion complexes.

Scanning electron microscopy and atomic force microscopy imaging of solid lipid nanoparticles derived from amphiphilic cyclodextrins.

Scanning electron microscopy (SEM) and atomic force microscopy (AFM) have been applied to the imagery of solid lipid nanoparticles (SLNs) formulated from an amphiphilic cyclodextrin, 2,3-di-o-alkanoyl-beta-cyclodextrin, beta-CD21C6. Comparison of the results shows that the vacuum drying technique used in sample preparation for SEM causes shrinkage in the size of the SLNs, whereas the deposition method used for AFM causes the SLNs to form small clusters. The hydrodynamic diameter determined from photon correlation spectroscopy (PCS) is 359+/-15 nm and the zeta potential is -25 mV.

Interfacial interactions between amphiphilic cyclodextrins and physiologically relevant cations.

The compression isotherms of a series of amphiphilic cyclodextrins, formed (a) by acylation at the secondary hydroxyl face and (b) by acylation accompanied by varying degrees of sulfatation (DS) at the primary hydroxyl face (DS=0, 4, and 7), have been studied on subphases of pure water and of water containing NaCl, KCl, MgCl(2), and CaCl(2) at inter- and extracellular concentrations. The formation of solid lipid nanoparticles (SLNs) by two of the molecules has been observed, while these do not aggregate at concentrations of monovalent salts up to 150 mM for the sulfated derivative. In the presence of divalent salts one of these with a DS=0 for sulfatation degree flocculates at divalent salt concentrations below 0.

Molecular recognition by Kluyveromyces of amphotericin B-loaded, galactose-tagged, poly (lactic acid) microspheres.

In an effort to develop a new way of drug delivery, especially for polyenic antifungal molecules, we have incorporated amphotericin B (AmB) into biodegradable galactosylated poly (L-lactic acid) (L-PLA) and poly (L-lactic-co-glycolic acid) (PLGA) microspheres. These drug carriers were prepared by solvent evaporation using an oil/water (o/w) emulsion. The ratio of galactosyl spacers with different chain lengths was 1.