Significant improvement of phase-change perfluorocarbon microdroplets (MDs) in the vast theranostic scenario passes through the optimization of the MDs composition with respect to synthesis efficiency, stability, and drug delivery capability. To this aim, decafluoropentane (DFP) MDs stabilized by a shell of dimethyldioctadecylammonium bromide (DDAB) cationic surfactant were designed. A high concentration of DDAB-MDs was readily obtained within a few seconds by pulsed high-power insonation, resulting in low polydisperse 1 µm size droplets. Highly positive ζ-potential, together with a long, saturated hydrocarbon chains of the DDAB shell, are key factors to stabilize the droplet and the drug cargo therein. The high affinity of the DDAB shell with cell plasma membrane allows for localized chemotherapeutics delivery by increasing the drug concentration at the tumor cell interface and boosting the uptake. This would turn DDAB-MDs into a relevant drug delivery tool exhibiting high antitumor activity at very low drug doses. In this work, the efficacy of such an approach is shown to dramatically improve the effect of doxorubicin against 3D spheroids of mammalian tumor cells, MDA-MB-231. The use of three-dimensional (3D) cell cultures developed in the form of multicellular tumor spheroids (i.e., densely packed cells in a spherical shape) has numerous advantages compared to 2D cell cultures: in addition to have the potential to bridge the gap between conventional in vitro studies and animal testing, it will improve the ability to perform more predictive in vitro screening assays for preclinical drug development or evaluate the potential of off-label drugs and new co-targeting strategies.

Phase change Dimethyldioctadecylammonium-Shelled microdroplets as a promising drug delivery system. Results on 3D spheroids of mammalian tumor cells / Tortorella, Elisabetta; Palmieri, Damiano; Piermarini, Martina; Gigante, Daniele; Oddo, Letizia; Toumia, Yosra; Paradossi, Gaio; Domenici, Fabio. - In: JOURNAL OF VISUALIZED EXPERIMENTS. - ISSN 1940-087X. - 169:(2021), pp. 1-20. [10.3791/62255]

Phase change Dimethyldioctadecylammonium-Shelled microdroplets as a promising drug delivery system. Results on 3D spheroids of mammalian tumor cells

Elisabetta Tortorella
Primo
;
2021

Abstract

Significant improvement of phase-change perfluorocarbon microdroplets (MDs) in the vast theranostic scenario passes through the optimization of the MDs composition with respect to synthesis efficiency, stability, and drug delivery capability. To this aim, decafluoropentane (DFP) MDs stabilized by a shell of dimethyldioctadecylammonium bromide (DDAB) cationic surfactant were designed. A high concentration of DDAB-MDs was readily obtained within a few seconds by pulsed high-power insonation, resulting in low polydisperse 1 µm size droplets. Highly positive ζ-potential, together with a long, saturated hydrocarbon chains of the DDAB shell, are key factors to stabilize the droplet and the drug cargo therein. The high affinity of the DDAB shell with cell plasma membrane allows for localized chemotherapeutics delivery by increasing the drug concentration at the tumor cell interface and boosting the uptake. This would turn DDAB-MDs into a relevant drug delivery tool exhibiting high antitumor activity at very low drug doses. In this work, the efficacy of such an approach is shown to dramatically improve the effect of doxorubicin against 3D spheroids of mammalian tumor cells, MDA-MB-231. The use of three-dimensional (3D) cell cultures developed in the form of multicellular tumor spheroids (i.e., densely packed cells in a spherical shape) has numerous advantages compared to 2D cell cultures: in addition to have the potential to bridge the gap between conventional in vitro studies and animal testing, it will improve the ability to perform more predictive in vitro screening assays for preclinical drug development or evaluate the potential of off-label drugs and new co-targeting strategies.
2021
microdroplets; drug delivery; 3D cell culture
01 Pubblicazione su rivista::01a Articolo in rivista
Phase change Dimethyldioctadecylammonium-Shelled microdroplets as a promising drug delivery system. Results on 3D spheroids of mammalian tumor cells / Tortorella, Elisabetta; Palmieri, Damiano; Piermarini, Martina; Gigante, Daniele; Oddo, Letizia; Toumia, Yosra; Paradossi, Gaio; Domenici, Fabio. - In: JOURNAL OF VISUALIZED EXPERIMENTS. - ISSN 1940-087X. - 169:(2021), pp. 1-20. [10.3791/62255]
File allegati a questo prodotto
File Dimensione Formato  
Tortorella_Jove-protocol_2021.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.27 MB
Formato Adobe PDF
1.27 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1518578
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact