New potential nanotechnology-based therapies for the treatment of rheumatoid arthritis

This thesis project covers the design, development and in vivo evaluation of a novel self-assembled injectable biodegradable drug delivery system (DDS). The system is composed of in situ hydrogel combined with nanocapsules for lipophilic anti-inflammatory drugs, aiming prolonged intra-articular (IA)...

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Detalhes bibliográficos
Autor: Storozhylova, Nataliya
Formato: tesis doctoral
Fecha de publicación:2018
País:España
Recursos:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/16762
Acesso em linha:http://hdl.handle.net/10347/16762
Access Level:acceso abierto
Palavra-chave:Materias::Investigación::32 Ciencias médicas::3209 Farmacología::320908 Preparación de medicamentos
Materias::Investigación::33 Ciencias tecnológicas::3399 Otras especialidades tecnológicas (Pharmaceutical technology)
Descrição
Resumo:This thesis project covers the design, development and in vivo evaluation of a novel self-assembled injectable biodegradable drug delivery system (DDS). The system is composed of in situ hydrogel combined with nanocapsules for lipophilic anti-inflammatory drugs, aiming prolonged intra-articular (IA) residence time and controlled drug release. The moderate initial viscosity allows good syringeability, while rheological properties of the assembled DDS enable resistance to high deformations, displaying the hydrogel suitable for IA application. In this regard, to validate the new delivery system, dexamethasone was used as a model drug. Besides, a novel and potential lead compound for immunotherapeutic anti-rheumatic drug candidate – galectin-3 antagonist – was synthesized, characterized and evaluated in this study. The preliminary in vivo results demonstrated remarkable suppression of acute joint inflammation by galectin-3 inhibitor encapsulated within hydrogel and administrated IA at microgram scale doses compared to the non-treated control. Overall, the work presented here portrays the DDS with encapsulated synthetic galectin-3 inhibitor as a capable in situ nanotechnology-based platform for arthropathies treatment, intended to contribute to efficient joints therapies.