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

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.