Iontophoretic drug delivery to the nail

Basic information about nail behaviour, under passive and especially iontophoretic condition, lacks in the literature. Thus, this thesis aims to fill gaps in the nail understanding by studying the potential and feasibility of the application of iontophoresis to human nail. The iontophoretic and passive delivery of Sodium Fluorescein (SF) and Nile Blue Chloride (NBC) were studied, in vitro, in order to determine their pathways as well as their depth and uniformity of penetration into the nail. The permselective properties of the nail were investigated by characterizing the contribution of electroosmosis, using mannitol as a marker, and by studying the flux of two inorganic cations, sodium and lithium, during in vitro experiments. Finally, the feasibility of transungual iontophoresis and the extraction of sodium and chloride ions from the body through the nail plate were performed on a group of human volunteers. Iontophoresis led the fluorescent markers slightly deeper into the nail plate than passive diffusion. The delivery of the bianion and of the cation was not different. Both compounds mainly penetrated the nail via the transcellular pathway. Electroosmosis resulted only in a slight enhancement of the mannitol fluxes compared to passive diffusion and the fluxes presented high variability, especially at pH 7.4 and when the current was applied in the anode-to-cathode direction. The delivery of the two inorganic cations was significantly higher at pH 7.0 than at pH 4.0 and supported that nails hold a negative charge at physiological pH. Ions were easily extractable through the nail plate during in vivo iontophoresis and all volunteers' feedbacks supported iontophoresis as an acceptable technique. This thesis demonstrated the feasibility and potential of in vivo transungual iontophoresis.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Synthèse de modèles de métabolites à l'aide de catalyseurs biomimétiques porphyriniques (cas d'un modèle d'acronycine)

ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Etude de l'amélioration de l'absorption par voie orale du nimésulide sous forme de composés d'inclusion avec les cyclodextrines dispersées ou non dans le macrogol 6000

Le nimésulide est un AINS (Anti-Inflammatoire Non Stéroïdien) qui présente une activité sélective sur la Cox 2 (CycloOxygénase de type 2), enzyme induite lors d'une inflammation. Cette caractéristique signe tout l'intérêt de cette méthode. Mais c'est aussi une molécule très peu hydrosoluble ce qui limite son absorption. Les cyclodextrines sont des oligosaccharides cycliques capables de former des composés d'inclusion avec des molécules hydrophobes. Les propriétés de la molécule complexée sont généralement modifiés lors de cette association : amélioration de l'hydrodrosolubilité, de l'absorption, modification du profil de tolérance. Le macrogol 6000 est un polymère hydrophile capable de former des dispersions solides. L'état de dispersion solide permet généralement une amélioration du profil de dissolution du produit ainsi dispersé. Afin de tester l'influence des cyclodextrines et /ou du macrogol 6000 sur l'absorption du nimésulide, des complexes d'inclusion ont été préparés avec quatre cyclodextrines (b-, g-, HPb- et PMb-cyclodextrines) et des complexes ternaires ont été préparés selon deux méthodes différentes. Ces essais ont permis de constater une amélioration très satisfaisante du profil de dissolution et de l'absorption par voie orale du nimésulide sous ses différentes formes hydrophilisées.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Nimesulide/cyclodextrin/PEG 6000 ternary complexes: physico-chemical characterization, dissolution studies and bioavailability in rats

International audiencePurpose :Ternary solid dispersions were prepared in order to estimate the effect of a double hydrophilization by cyclodextrins and PEG 6000 on nimesulide apparent characteristics. Ternary solid dispersions of nimesulide, cyclodextrins and PEG 6000 were characterized using DSC, FT-IR, dissolution studies and evaluating the bioavailability in rats.Methods :Ternary solid dispersions were prepared either using native powders or using a preformed inclusion complex of nimesulide and cyclodextrin. Inclusion complexes and pure drug were used as references. Circulating nimesulide was measured out in rat plasma after orally administration of our different products (ternary solid dispersions, inclusion complexes and pure drug).Results :An improvement of the nimesulide dissolution rate was obtained with inclusion complexes and ternary solid dispersion. In rat plasma, inclusion complexes and ternary solid dispersion improved T max.Conclusions :A second hydrophilization of inclusion complexes by PEG 6000 does not allow to achieve better results concerning nimesulide concentration in rat plasma or in dissolution studies than with inclusion complexes alone

Confocal microscopy for healthy and pathological nail

Nail diseases are often annoying for the patient and diagnostically challenging for dermatologists. New imaging techniques are of high interest in the diagnosis of nail disorders to reduce the number of nail biopsies. Confocal microscopy is a high-resolution emerging imaging technique that can be used to explore the entire body surface, including skin, mucosa, hair and nails. A systematic review of the literature concerning the use of confocal microscopy for the study of either healthy or pathological nail has been performed to evaluate the current use of this technique and possible future applications. Confocal microscopy is particularly suitable for nails because it allows a non-invasive in vivo examination of this sensitive body area, and nail plate transparency permits to image up to the nail bed with an easy identification of corneocytes. Confocal microscopy can play a role in the diagnosis of onychomycosis and melanonichia, and in the study of drug penetration through the nail plate. It could be used in the future as a non-invasive procedure for the investigation of different nail diseases, such as psoriasis and lichen planus. Further application could be the intra-operative ex vivo examination of nail specimens to outline tumour margins to assist surgery