On the intracellular release mechanism of hydrophobic cargo and its relation to the biodegradation behavior of mesoporous silica nanocarriers.
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 real-time 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.
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, BioCity, Tykistökatu 6A, FI 20520 Turku, Finland.
Eva
E
von Haartman
Center for Functional Materials, Laboratory of Physical Chemistry, Faculty of Science and Engineering, Åbo Akademi University, Porthaninkatu 3-5, FI 20500 Turku, Finland.
Desiré
D
Lindberg
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, BioCity, Tykistökatu 6A, FI 20520 Turku, Finland; Laboratory of Biophysics, University of Turku, Tykistökatu 6A, FI 20520 Turku, Finland.
Neeraj
N
Prabhakar
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, BioCity, Tykistökatu 6A, FI 20520 Turku, Finland. Electronic address: jerosenh@abo.fi.
Jessica M
JM
Rosenholm
D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D065546:Drug Liberation / Q000502:physiology*; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007424:Intracellular Fluid / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry / Q000378:metabolism*
D004337:Drug Carriers; D005456:Fluorescent Dyes; D012822:Silicon Dioxide
Biodegradation; Drug delivery systems; Drug release; Intracellular drug delivery; Mesoporous silica nanoparticles