No description available.

<p>With the studies performed in this theses the local drug delivery technique FibMat developed by the biotech company AddBIO, was shown to be applicable to other plasma proteins and drugs than the fibrinogen-bisphosphonate combination that is today being commercialized. Hence the potential for a broader field of application was demonstrated. The application targeted today is as a surface modification giving improved strength to bone around screws used in bone implants. The effect of changing protein and manufacturing conditions was studied with null ellipsometry. It was demonstrated that with changes in incubation temperature, pH and salinity the fibrinogen could be successfully exchanged for the plasma proteins human serum albumin and immunoglobulin G. With liquid scintillation counting it was shown that the developed protein multilayers were able to absorb and release the bone strengthening drug alendronic acid in levels comparable to that of the fibrinogen based ditto. Disk susceptibility tests with the bacteria S. Aureus showed a potential for antibacterial functionalization with gentamicin. The release was, in the case of the fibrinogen multilayer, detectable up to 48 hours. Similar test revealed an inability of silver nanoparticle incorporated protein multilayers to achieve inhibitory levels.</p>

With the studies performed in this theses the local drug delivery technique FibMat developed by the biotech company AddBIO, was shown to be applicable to other plasma proteins and drugs than the fibrinogen-bisphosphonate combination that is today being commercialized. Hence the potential for a broader field of application was demonstrated. The application targeted today is as a surface modification giving improved strength to bone around screws used in bone implants. The effect of changing protein and manufacturing conditions was studied with null ellipsometry. It was demonstrated that with changes in incubation temperature, pH and salinity the fibrinogen could be successfully exchanged for the plasma proteins human serum albumin and immunoglobulin G. With liquid scintillation counting it was shown that the developed protein multilayers were able to absorb and release the bone strengthening drug alendronic acid in levels comparable to that of the fibrinogen based ditto. Disk susceptibility tests with the bacteria S. Aureus showed a potential for antibacterial functionalization with gentamicin. The release was, in the case of the fibrinogen multilayer, detectable up to 48 hours. Similar test revealed an inability of silver nanoparticle incorporated protein multilayers to achieve inhibitory levels.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Les traitements des pathologies de l’oreille interne par voie locale se développent en alternative aux traitements par voie générale peu efficaces et responsables de nombreux effets secondaires. Dans ce travail, nous avons développé une formulation originale constituée de liposomes dispersés au sein d’un gel d’acide hyaluronique pour la libération prolongée d’un corticoïde dans l’oreille interne après administration locale dans l’oreille moyenne. D'abord, une étude physicochimique approfondie a permis d'identifier les paramètres clés de formulation qui ont un impact sur les propriétés du gel de liposomes en termes de caractéristiques rhéologiques, de seringabilité, de stabilité, de microstructure et enfin de diffusion des liposomes dans le gel. Ensuite, le gel de liposomes contenant la dexamethsone phosphate a été évalué in vivo chez le cobaye. L'administration locale du gel de liposomes a abouti à une libération prolongée du corticoïde dans l'oreille interne, sans aucun effet négatif sur la fonction auditive. L’évaluation de l’efficacité thérapeutique de la formulation pour le traitement de la surdité secondaire à un traumatisme sonore et pour la préservation de l’audition durant l’implantation cochléaire a montré des résultats préliminaires très prometteurs. / Local, rather than systemic drug delivery is being developed to treat inner ear diseases. In this work, we developed an original drug delivery system based on liposomes dispersed within a hyaluronic acid gel for the sustained delivery of a corticoid to the inner ear after local administration in the middle ear. First, a thorough physicochemical study allowed to identify the key formulation parameters that impact the liposomal gel properties in terms of rheological behavior, syringeability, stability, microstructure and diffusion of liposomes within the gel. Then, the liposomal gel containing dexamethsone phosphate was evaluated in vivo in guinea pig. The local administration of the liposomal gel in the middle ear resulted in a sustained release of the corticoid in the inner ear without any negative effect on the hearing function. Promising preliminary data were obtained regarding the therapeutic efficacy of the formulation for hearing recovery after acoustic trauma and for hearing preservation during cochlear implantation.

No description available.

No description available.

No description available.