Safety evaluation of novel polymeric nanocarriers for drug delivery using human osteoblasts

Dias, Kamila; Louro, Henriqueta; Gonçalves, Lídia; Bettencourt, Ana; Silva, Maria João

http://hdl.handle.net/10400.18/4786

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Abstract(s)

The development of novel nanocarriers has been recognized as a promising approach to improve drug release profiles on targeted sites, being the assessment of their biocompatibility and safety a critical point of the process. The objective of this work was to characterize the cellular interactions and the potential toxicity of the novel developed polymeric nanoparticles (NPs), using human osteoblasts. For this purpose, Poly(methyl methacrylate) (PMMA) and PMMA-Eudragit RL 100 (PMMA-Eud, 50:50) NPs were produced and their physicochemical properties were characterized. The safety evaluation of both NPs was conducted through the characterization of cellular uptake (fluorescence microscopy), cyto- and genotoxicity (MTT, Comet and Micronucleus assays) using both normal and differentiated osteoblast cell line (MG-63-ATCC®CRL-1427™). The results confirmed the successful uptake of PMMA and PMMA-Eud by the cells. Both NPs were not cytotoxic in differentiated cells, although a moderate toxicity was detected in undifferentiated cells. As to their genotoxic potential, NPs induced primary DNA damage in osteoblasts, especially under a short-term exposure. Noteworthy, none of the NPs caused chromosome breaks, indicating that the primary DNA lesions were not converted into permanent genetic damage. On the other hand, an increased cell proliferative capacity was noted for PMMA-NPs, which deserves further investigation. In conclusion, the safety assessment of the two NPs indicated that both are biocompatible but display a weak genotoxicity that should be explored in other in vitro endpoints, e.g., gene mutation, and in vivo studies. Moreover, understanding how physicochemical features relate to toxicity will support the design of safer formulations for biomedical purposes.