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Article Dans Une Revue International Journal of Pharmaceutics Année : 2022

Before in vivo studies: In vitro screening of sphingomyelin nanosystems using a relevant 3D multicellular pancreatic tumor spheroid model

Sainza Lores
  • Fonction : Auteur
Valérie Nicolas
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  • PersonId : 1097423
Severine Domenichini
  • Fonction : Auteur
Rafael López
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María de La Fuente
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Résumé

Sphingomyelin nanosystems have already shown to be promising carriers for efficient delivery of anticancer drugs. For further application in the treatment of pancreatic tumor, the investigation on relevant in vitro models able to reproduce its physio-pathological complexity is mandatory. Accordingly, a 3D heterotype spheroid model of pancreatic tumor has been herein constructed to investigate the potential of bare and polyethylene glycol-modified lipid nanosystems in terms of their ability to penetrate the tumor mass and deliver drugs. Regardless of their surface properties, the lipid nanosystems successfully diffused through the spheroid without inducing toxicity, showing a clear safety profile. Loading of the bare nanosystems with a lipid prodrug of gemcitabine was used to evaluate their therapeutic potential. While the nanosystems were more effective than the free drug on 2D cell monocultures, this advantage, despite their efficient penetration capacity, was lost in the 3D tumor model. The latter, being able to mimic the tumor and its microenvironment, was capable to provide a more realistic information on the cell sensitivity to treatments. These results highlight the importance of using appropriate 3D tumor models as tools for proper in vitro evaluation of nanomedicine efficacy and their timely optimisation, so as to identify the best candidates for later in vivo evaluation.
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Dates et versions

hal-04348370 , version 1 (03-05-2024)

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Nadege Bidan, Sainza Lores, Aure Vanhecke, Valérie Nicolas, Severine Domenichini, et al.. Before in vivo studies: In vitro screening of sphingomyelin nanosystems using a relevant 3D multicellular pancreatic tumor spheroid model. International Journal of Pharmaceutics, 2022, ⟨10.1016/j.ijpharm.2022.121577⟩. ⟨hal-04348370⟩
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