Utilize este identificador para referenciar este registo: http://hdl.handle.net/10362/22042
Título: Safety Assessment of Polymeric Nanoparticle Carriers for Drug Delivery in Human Osteoblasts
Autor: Dias, Kamila Kappke
Orientador: Silva, Maria João
Bettencourt, Ana
Palavras-chave: Nanocarriers
PMMA
PMMA-Eud
Safety evaluation
Nanotoxicology
Osteoblasts
Data de Defesa: Mar-2017
Resumo: Nanoparticles (NPs) applied to pharmaceutics constitute an innovative approach to improve drug release profiles on targeted sites. The assessment of their biocompatibility and safety for human health plays also a major role in the development process. The objective of this work was to characterize the cellular interactions and potential toxicity of polymeric nanoparticles, in human osteoblasts. Poly(methyl methacrylate) (PMMA) and Eudragit® RL 100 (Eud) were used to produce PMMA and PMMA-Eud (50:50) NPs (average size range of 500 nm) by single-emulsion with solvent evaporation methodology. Their physicochemical properties (size distribution, surface charge, morphology and aggregation/agglomeration states) were analysed. Their safety evaluation was conducted in “normal” and differentiated MG63 cells. Cell uptake, cyto- and genotoxicity were characterized using several endpoints: cell viability (MTT assay), oxidative stress production (H2DCFDA assay), DNA and chromosome damage (Comet and Micronucleus assays). The results confirmed the successful cellular uptake of PMMA and PMMA-Eud. Both NPs were neither cytotoxic nor able to produce oxidative stress in differentiated cells, although a moderated toxicity was detected in undifferentiated cells. As to the genotoxic potential, both NPs induced primary DNA damage (comet assay) in osteoblasts, especially in short-term exposure. Noteworthy, none of the NPs caused chromosome alterations, indicating that the DNA lesions were not converted into permanent genetic damage. However, an increased cell proliferative capacity was noted for PMMA that needs confirmation. In conclusion, PMMA and PMMA-Eud are promising nanocarriers in drug delivery systems. Their in vitro safety assessment in osteoblasts indicated that both NPs are biocompatible but display a weak genotoxicity that needs further investigation, e.g., using other endpoints or in vivo models. The utilization of cells under different specialization status improved data reliability. Moreover, understanding how physicochemical features relate to toxicity will support the design of safer formulations for biomedical purposes as envisaged by the safer-by-design concept.
URI: http://hdl.handle.net/10362/22042
Designação: Master Degree in Biochemistry for Health
Aparece nas colecções:FCT: DQ - Dissertações de Mestrado

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