Denis Wouessidjewe

Antimitotic and antiproliferative activities of chalcones: forward structure-activity relationship

A series of 59 chalcones was prepared and evaluated for the antimitotic effect against K562 leukemia cells. The most active chalcones were evaluated for their antiproliferative activity against a panel of 11 human and murine cell cancer lines. We found that three chalcones were of great interest as potential antimitotic drugs. In vivo safety studies conducted on one of the most active chalcones revealed that the compound was safe, allowing further in vivo antitumor evaluation.

Pharmaceutical Uses of Cyclodextrins and Derivatives

AbstractDue to their particular conformation, cyclodextrins have the remarkable characteristic of being able to include various kinds of molecule inside their hydrophobic cavity, conferring on them an environmental hydrophily. These inclusion compounds have completely new pharmacotechnical properties, but the most important ones concern increases in water solubility and bioavailability. When administered orally, the inclusion compounds decompose, allowing the free active ingredient to be absorbed by the gastro-intestinal mucosa. However, a certain proportion of inclusion compound is absorbed without any dissociation.Some cyclodextrin derivatives are very interesting because of their very high water solubility, and also because of their low parenteral toxicity compared with the original β-cyclodextrin. However, in parenteral administration, it is absolutely necessary to study the pharmacokinetic and pharmacological characteristics of the inclusion compound, which must be considered as the true active ingre...

Bioadhesive analysis of controlled-release systems. III. Bioadhesive and release behavior of metronidazole-containing poly(acrylic acid)-hydroxypropyl methylcellulose systems

Abstract Bioadhesive controlled release systems for the delivery of metronidazole were prepared by compression of hydroxypropyl methylcellulose with poly(acrylic acid), which served as the bioactive adhesive compound. The release behavior of systems containing 50 wt% metronidazole and various amounts of the two polymers was found to be non-Fickian. The bioadhesive strength of the bond formed between surface-preswollen systems and the sublingual bovine mucus was determined by novel tensile experiments and it was found to be dependent on the poly( acrylic acid) content.

Evaluation of the cytotoxicity of cyclodextrins and hydroxypropylated derivatives

Abstract The haemolytic effect toward human erythrocytes and the cytotoxicity toward P388 cells of the three natural cyclodextrins and their hydroxypropylated derivatives have been compared. The cytotoxicity of the six cyclodextrins toward these two cell types follows a similar pattern, and the curve parameters are generally of the same order of magnitude for both cell types in spite of the biological differences. The in vitro cytotoxic effect decreases in the order βCD > αCD > γCD and HPβCD > HPγCD > = HPαCD. These results showed that phenomena involved in cyclodextrin cytotoxicity are not specific to the cell type, and bore out the hypothesis of destruction of membranes by the removal of basic membrane components. Moreover, they demonstrated the influence of parameters other than CD concentration, i.e., the presence of serum components, or the density of the cells, which can dramatically influence the cytotoxic effect of CDs. In fact, the cytotoxicity of a cyclodextrin is determined by the relative proportion of cellular and extracellular molecules likely to be included and cyclodextrins.

Development of a new colloidal drug carrier from chemically-modified cyclodextrins: Nanospheres and influence of physicochemical and technological factors on particle size

Abstract A new nanosphere carrier system has been obtained from amphiphilic β-cyclodextrin (fatty acid chains varying from 2 to 14 carbons grafted at the O 2 and O 3 positions of β-cyclodextrin). The nanospheres, with a mean diameter varying between 90 and 150 nm, are prepared by progressive dispersion of an organic solution of modified β-cyclodextrin in an aqueous phase with or without surfactant. Various physicochemical parameters have been studied: the effect of the chain length of acyl groups (βCD with 6, 12 and 14 fatty acid carbons), and type of surfactant on the size and physicochemical properties and stability of the nanospheres. A preliminary investigation of water-soluble and insoluble drug entrapment by nanospheres was carried out.

Indomethacin and cyclodextrin complexes

Abstract Different complexes of indomethacin and both β-cyclodextrin (βCD) and hydroxypropyl jS-cyclodextrin (HPβCD) were prepared using different methods: kneading, spray-drying and neutralization followed by freeze-drying. The complexes obtained were studied in the solid phase by differential scanning calorimetry (DSC), thermomicroscopy (TM), and infrared spectroscopy (IR), and in the liquid phase by 1 H-NMR. The results showed that the nature of the end products depends on the method of preparation. The neutralization technique led to a true inclusion of sodium indomethacin in the cyclodextrin cavity, while the nature of the spray-dried product, indomethacin (acid form)/cyclodextrin, was not well defined. The kneading method did not lead to a real inclusion. In any case, the complexes obtained may be of great value as rapidly dissolving forms of indomethacin in water.

Bioadhesive Tablets Influence of the Testing Medium Composition on Bioadhesion

AbstractA bioadhesive tablet of metronidazole has been developed for oral or vaginal administration. The bioadhesive component is poly(acrylic acid) (Carbopol 934), and the matrix component is hydroxypropyl methylcellulose (HPMC K4M). The influence of the test medium was investigated in order to determine the adhesion of the tablet during routine use by the various routes. The parameter retained to evaluate adhesion was the adhesion work on a biological tissue. The factors whose influence was investigated were pH, ionic force and nature of cations, and type of biological substrate

Evaluation of gastrointestinal behaviour in the rat of amphiphilic β-cyclodextrin nanocapsules, loaded with indomethacin

Abstract With a view to investigating the role of encapsulation of indomethacin within modified β-cyclodextrin (βCD-C6) nanocapsules, we prepared nanocapsules with indomethacin as a model drug. These particles had an average size of 194 nm and encapsulated approximately 99% of indomethacin. The encapsulation of indomethacin within orally administered βCD-C6 nanocapsules protected against both gastric and intestinal ulceration is compared with an oral administration of an aqueous solution of Indocid®. The relative bioavailability was also increased by this encapsulation.

Industrial Uses of Cyclodextrins and Their Derivatives

Abstract Cyclodextrins as well as their derivatives have the ability of encapsulating in their cavity a wide variety of molecules, conferring on them new physicochemical characteristics. For this reason, they are proposed for many uses in various industries. When they are empty, they can be used for their ability to trap certain molecules, or because they can transform gases or liquids into solids, improve stability, decrease undesirable side effects, enhance solubility, increase absorption through biological membranes, and prolong the release of the encapsulated molecule.

Characterization of amphiphilic β-cyclodextrin nanospheres

Abstract A new nanosphere carrier system was obtained from amphiphilic β-cyclodextrins bearing fatty acids (with a chain length of either 6 or 12 or 14 carbon atoms) grafted at the O2 and O3 position of the β-cyclodextrin molecule. Nanospheres, with a mean diameter of several hundred nm, were prepared by progressive dispersion. The nanospheres were characterized by their density, surface charge, size and morphology, using several techniques, namely centrifugation, zeta potential determination, quasi-elastic light scattering and freeze-fracture electron microscopy.