Élaboration d'un vecteur nanoparticulaire liposomial par assemblage supramoléculaire d'un dérivé adamantyle et de cyclodextrine modifiée (application à la barrière hémato-encéphalique)

Les maladies cérébrales ont connu un intérêt croissant dans la communauté scientifique ces dix dernières années en raison de leur impact sur notre société en termes de santé public et de facteurs économiques. En particulier, des stratégies ont eu comme objectif de délivrer des principes actifs à travers les cellules endothéliales de la barrière hémato-encéphalique (B.H.E.), l'une d'entre elles consistant à encapsuler le médicament dans des nanoparticules telles que des liposomes. Pour augmenter la délivrance de ces vecteurs nanoparticulaires et comprendre le mécanisme de leur transport à travers la B.H.E., une nouvelle approche supramoléculaire a été développée. Des molécules gluco-adamantoylées ont été synthétisées et incluses, via la partie adamantoyle, dans la cavité d'alkylammonium b-cyclodextrines (b-CD) amphiphiles dont la longueur de la chaîne alkyle varie de 2 à 16 carbones. La partie glucosidique est censée jouer le rôle de ligand vis-à-vis des récepteurs de la B.H.E.. Les complexes hôte/invité résultants ont été totalement caractérisés par des mesures RMN qui ont révélées une inclusion de la partie adamantoyle concomitante à un processus de reconnaissance intra-moléculaire de la chaîne alkyle dans la cavité de la CD. Lorsque ces assemblages supramoléculaires ont été mélangés à des liposomes cholesteryl-dipalmitoylphosphatidylcholine(DPPC), la chaîne alkyle est exclue de la cavité et est incorporée dans la bicouche lipidique. Le liposome modifié en surface ainsi obtenu a montré de grandes potentialités de transport sur un modèle in vitro de la B.H.E. puisque 30% de ces liposomes ont réussi à pénétrer dans les cellules endothéliales.Cerebral diseases have attracted a growing interest among the scientific community during these last ten years because of their impact on our society in terms on public health and economic factors. In particular, strategies have been targeted at delivering drugs through the endothelial cells of the blood brain barrier (B.B.B.), one of them consisting in encapsulating drugs inside nanoparticules such as liposomes. To increase the delivery of these nanoparticular vectors and understand the mechanism of their transport through the B.B.B., a new supramolecular approach has been developed. Gluco-adamantoyl molecules have been synthesized and included, via the adamantoyl moiety, inside the cavity of amphiphilic alkylammonium b-cyclodextrins (b-CD) in which alkyl chain length ranges from 2 to 16 carbons. The glucosidic moiety is expected to play the role of ligand towards the receptors of the B.B.B.. The resulting host-guest complexes have been fully characterized by NMR measurements which revealed a concomitant inclusion of the adamantoyl part and an intra-molecular recognition process of the alkyl chain in the CD cavity. When mixing these supramolecular assemblies with cholesteryl-dipalmitoylphosphatidylcholine(DPPC) liposomes, the alkyl chain was excluded from the CD cavity and is incorporated in the lipidic bilayer. The obtained surface-modified liposomes have shown great potentialities of transport on a in vitro model of B.B.B. since 30% of these liposomes succeeded in penetrating the endothelial cells.LENS-BU Sciences (624982102) / SudocSudocFranceF

Phosphane-Based Cyclodextrins as Mass Transfer Agents and Ligands for Aqueous Organometallic Catalysis

The replacement of hazardous solvents and the utilization of catalytic processes are two key points of the green chemistry movement, so aqueous organometallic catalytic processes are of great interest in this context. Nevertheless, these processes require not only the use of water-soluble ligands such as phosphanes to solubilise the transition metals in water, but also the use of mass transfer agents to increase the solubility of organic substrates in water. In this context, phosphanes based on a cyclodextrin skeleton are an interesting alternative since these compounds can simultaneously act as mass transfer agents and as coordinating species towards transition metals. For twenty years, various cyclodextrin-functionalized phosphanes have been described in the literature. Nevertheless, while their coordinating properties towards transition metals and their catalytic properties were fully detailed, their mass transfer agent properties were much less discussed. As these mass transfer agent properties are directly linked to the availability of the cyclodextrin cavity, the aim of this review is to demonstrate that the nature of the reaction solvent and the nature of the linker between cyclodextrin and phosphorous moieties can deeply influence the recognition properties. In addition, the impact on the catalytic activity will be also discussed

A versatile liposome/cyclodextrin supramolecular carrier for drug delivery through the blood-brain barrier

International audienceFor many commercial drugs, reaching the central nervous system in large amount without damaging the blood-brain-barrier (BBB) remains a challenging task. We present here a supramolecular strategy aiming at using a well-defined cyclodextrincoated liposomes as drug carrier and adamantoyl saccharides as BBB-interacting ligands. In this study, the liposome is constituted of n-alkyldimethylammoniumcyclodextrins incorporated in the lipid bilayer of a 3/7 cholesterol/dipalmitoylphosphatidylcholine mixture and the ligand is constituted of an adamantoylglucose molecule whose adamantoyl moiety can be included in the CD cavity. The whole supramolecular assembly has been characterized by light-scattering and 31P NMR measurements. Toxicity and permeability studies on an in vitro model of the BBB clearly demonstrated a 5-fold improved ability of the modified liposome to enter the BBB-endothelial cells compared to the non-coated liposome. Fluorescence labelling of these liposomes is also displayed with DiI as a fluorescent probe

Cyclodextrin-Directed Synthesis of Gold-Modified TiO₂ Materials and Evaluation of Their Photocatalytic Activity in the Removal of a Pesticide from Water: Effect of Porosity and Particle Size

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