Máster en Investigación e Desenvolvemento de Medicamentos

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    Sistemas nanoparticulados de administración intraarticular para vectorización de macrófagos sinoviales
    (2019) Martínez Borrajo, Rebeca; Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica; Díaz Rodríguez, Patricia; Landín Pérez, Mariana
    [EN]Osteoarthritis (OA) is highly prevalent disease worldwide, curses with pain and functional disability characterized by synovium inflammation as a result of the progressive cartilage destruction. Macrophages seem to have a pivotal role at the onset and development of this disease involved in the inflammatory process. When a cartilage lesion occurs, macrophages release pro-inflammatory mediators leading to cartilage destruction. Current OA therapy includes intraarticular corticosteroids and hyaluronic acid administration aiming at improving the pathology symptomatology, but without improvement in the cartilage regeneration due to, partially, the rapid clearance on the joint cavity. The aim of this work is to target synovial macrophages involved in OA through the intraarticular administration of nanoparticulated systems. To this end, nanostructured lipid carriers (NLCs) loaded with an anti-inflammatory drug were developed using artificial neural networks (ANN), the cellular response of those systems was analyzed in human macrophages and chondrocytes from patients with OA. The experimental results showed the developed systems had adequate characteristics of size and zeta potential with capacity to load the antiinflamatory drug β-Lapachone. The use of neural networks has allowed to choose the formulation composition able to fulfill the desired characteristics for intra-articular administration. The optimized formulation showed similar characteristics to neural networks prediction and is stable for at least two weeks. In addition, functionalization of optimized NLCs with mannose increases macrophages internalization