Laponite-based nanogels for bone tissue regeneration: optimization and efficacy studies

• Autor(a) principal: Ferreira, Fátima José Mendes
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.13/2986
• topic: Osteoporose; Bisfosfonatos; Alendronato; Laponite; Nanotecnologia; Osteoporosis; Bisphosphonates; Alendronate; Nanotechnology; Applied Biochemistry; .; Faculdade de Ciências Exatas e da Engenharia; Domínio/Área Científica::Ciências Médicas

Osteoporosis is the most prevalent disease of the skeletal system, currently affecting millions of people worldwide, causing painful fractures that lead to costly treatments and often to morbidity and loss of independence. With life expectancies gradually increasing and a growing elder population, the incidence of the illness and cost of the treatments associated is expected to rise in the next decades. Out of the therapies currently available, bisphosphonates are the most prescribed, particularly alendronate, for their efficacy and their affordability. However, these drugs are associated with complicated drug regimens and adverse side effects that often discourage patients from correctly following the treatment, as well as low gastrointestinal absorption and bioavailability. Hence, Laponite®-based nanogels conjugated to bisphosphonates are here proposed as new targeted drug delivery systems to overcome the disadvantages associated with bisphosphonates, namely increasing their bioavailability and minimizing their side effects in the organism. The nanogels synthetized displayed high entrapment efficiency of alendronate, with the constituting nanoparticles measuring approximately 180 nm (hydrodynamic diameter), with polydispersity index of 0.4 and a zeta potential of about -51 mV. That size increases drastically when the nanogels are frozen and lyophilized, though it returns to values close to the initial ones, highlighting the nanogel’s restructuring properties. Alendronate was successfully conjugated to FITC and used to synthetize fluorescent-labelled nanogels to evaluate the kinetics of cellular uptake and internalization pathways. The preliminary results indicate a maximum uptake after 24 hours of incubation and internalization mainly through the macropinocytosis pathway. The conjugation to the nanogels decreased alendronate’s cytotoxicity in Human Mesenchymal Stem Cells and maintained its hemocompatibility. The osteogenic differentiation assays also revealed promising results, with improvements in all assays with exposure to the nanogel, which were also enhanced by the presence of Laponite®.