In vitro evaluation of the internalization and toxicological profile of silica nanoparticles and submicroparticles for the design of dermal drug delivery strategies.

Autor: Vicente S; SANOFI Research & Development, Translational Sciences Unit, 91385 Chilly-Mazarin, France., Moia C; Environmental Science and Technology Department, School of Applied Sciences, Cranfield University, Bedford, MK43 0AL, UK., Zhu H; Environmental Science and Technology Department, School of Applied Sciences, Cranfield University, Bedford, MK43 0AL, UK., Vigé X; SANOFI Research & Development, Translational Sciences Unit, 91385 Chilly-Mazarin, France.
Jazyk: angličtina
Zdroj: Journal of applied toxicology : JAT [J Appl Toxicol] 2017 Dec; Vol. 37 (12), pp. 1396-1407. Date of Electronic Publication: 2017 Jul 25.
DOI: 10.1002/jat.3507
Abstrakt: The use of colloidal silica nanoparticles and sub-microparticles (SiPs) have been considered a very interesting strategy for drug delivery applications. In the present study, we have focused our attention on the suitability of these nanomaterials as potential carriers for dermal drug delivery, thus studying their toxicological profile in vitro, cellular uptake and intracellular localization in both human keratinocytes (K17) and human dermal fibroblasts (HDF) as a function of their particle size (SiPs of 20, 70, 200 and 500 nm). Full characterization of these aspects enabled us to observe a strong cell-type dependency in terms of cytotoxicity and cell internalization, whereas particle size was only relevant for ultra-small SiPs (20 nm), being the most toxic SiPs. For 70, 200 and 500 nm SiPs, the differences in uptake and intracellular trafficking determined the different toxicological profiles in K17 and HDF. In addition, these characteristics can further define different drug delivery strategies. Hence, phagocytosis has been identified as the main internalization mechanism for K17, and caveolae-mediated endocytosis for HDF. This relevant information led us to conclude that fibroblasts would be optimal targets for delivering delicate therapeutic molecules such as proteins or genetic material using SiPs while maintaining a low toxicity profile, whereas keratinocytes could enable accelerated drug release therapies based on SiPs.
(Copyright © 2017 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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