A1 Refereed original research article in a scientific journal
On the intracellular release mechanism of hydrophobic cargo and its relation to the biodegradation behavior of mesoporous silica nanocarriers
Authors: von Haartman E, Lindberg D, Prabhakar N, Rosenholm JM
Publisher: Elsevier Science BV
Publishing place: Amsterdam
Publication year: 2016
Journal:: European Journal of Pharmaceutical Sciences
Journal name in source: EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Journal acronym: EUR J PHARM SCI
Volume: 95
First page : 17
Last page: 27
Number of pages: 11
ISSN: 0928-0987
eISSN: 1879-0720
DOI: https://doi.org/10.1016/j.ejps.2016.06.001
Web address : http://dx.doi.org/10.1016/j.ejps.2016.06.001
Abstract
The intracellular release mechanism of hydrophobic molecules from surface-functionalized mesoporous silica nanoparticles was studied in relation to the biodegradation behavior of the nanocarrier, with the purpose of determining the dominant release mechanism for the studied drug delivery system. To be able to follow the realtime intracellular release, a hydrophobic fluorescent dye was used as model drug molecule. The in vitro release of the dye was investigated under varying conditions in terms of pH, polarity, protein and lipid content, presence of hydrophobic structures and ultimately, in live cancer cells. Results of investigating the drug delivery system show that the degradation and drug release mechanisms display a clear interdependency in simple aqueous solvents. In pure aqueous media, the cargo release was primarily dependent on the degradation of the nanocarrier, while in complex media, mimicking intracellular conditions, the physicochemical properties of the cargo molecule itself and its interaction with the carrier and/or surrounding media were found to be the main release governing factors. Since the material degradation was retarded upon loading with hydrophobic guest molecules, the cargo could be efficiently delivered into live cancer cells and released intracellularly without pronounced premature release under extracellular conditions. From a rational design point of view, pinpointing the interdependency between these two processes can be of paramount importance considering future applications and fundamental understanding of the drug delivery system. (C) 2016 Elsevier B.V. All rights reserved.
The intracellular release mechanism of hydrophobic molecules from surface-functionalized mesoporous silica nanoparticles was studied in relation to the biodegradation behavior of the nanocarrier, with the purpose of determining the dominant release mechanism for the studied drug delivery system. To be able to follow the realtime intracellular release, a hydrophobic fluorescent dye was used as model drug molecule. The in vitro release of the dye was investigated under varying conditions in terms of pH, polarity, protein and lipid content, presence of hydrophobic structures and ultimately, in live cancer cells. Results of investigating the drug delivery system show that the degradation and drug release mechanisms display a clear interdependency in simple aqueous solvents. In pure aqueous media, the cargo release was primarily dependent on the degradation of the nanocarrier, while in complex media, mimicking intracellular conditions, the physicochemical properties of the cargo molecule itself and its interaction with the carrier and/or surrounding media were found to be the main release governing factors. Since the material degradation was retarded upon loading with hydrophobic guest molecules, the cargo could be efficiently delivered into live cancer cells and released intracellularly without pronounced premature release under extracellular conditions. From a rational design point of view, pinpointing the interdependency between these two processes can be of paramount importance considering future applications and fundamental understanding of the drug delivery system. (C) 2016 Elsevier B.V. All rights reserved.
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