Comparison of different silica microporous structures as drug delivery systems for in vitro models of solid tumors


Several silica microporous structures have been studied for their potential as drug delivery systems (DDS) over the last years. However, systematic studies comparing host structures with different topologies and particle sizes, and toxicity studies to human cancer cells, are scarce. In the present work, 3D crystalline structures, three different zeolites (large, medium and small pore size) and one titanosilicate (large pore size) were used as hosts for loading 5-fluorouracil (5-FU), an anticancer drug currently used to treat several malignant tumors. Here, we (i) compared the loading capacity and drug release profiles of the different hosts in simulated body fluid conditions, including host structure stability studies; (ii) established the kinetic parameters for the release of 5-FU and (iii) studied the effect of 5-FU encapsulation in the viability of human breast and colon cancer cells, with determination of the potentiation factor. The loading capacity and the release profile of the DDS were revealed to be dependent on the porous framework of the host structures. Decrease in pH to 2.0 (simulation of gastro-intestinal fluid), showed stability of the host structures, with minimal leaching of Al3+ and no Ti4+ for long periods of time (up to 72 h). All DDS drug release profiles fitted the Weibull model. These silica microporous structures were revealed to be non-toxic to the cancer cells, while all DDS endorsed the important 5-FU potentiation effect on cell viability.



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Vilaca, N; Machado, AF; Morais-Santos, F; Amorim, R; Neto, AP; Logodin, E; Pereira, MFR; Sardo, M; Rocha, J; Parpot, P; Fonseca, AM; Baltazar, F; Neves, IC

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N. V., F. M. S. and R. A. are recipients of PhD fellowships (SFRH/BD/97797/2013, SFRH/BD/87139/2012 and SFRH/BD/98002/2013) from Foundation for Science and Technology (FCT, Portugal). MS also acknowledges FCT for a post-doc grant (SFRH/BPD/65978/2009). This work has been developed under the scope of the project NORTE-01-0145-FEDER-000013 and the project BioTecNorte (operation NORTE-01-0145-FEDER-000004), supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work also has been funded by national funds (FCT), through the projects: Centre of Chemistry (UID/QUI/00686/2013 and UID/QUI/0686/2016); CICECO (PEst-C/CTM/LA0011/2013, F-COMP-01-0124-FEDER-037271); LSRE/LCM (POCI-01-0145-FEDER-006984) and ICVS/3B's (POCI-01-0145-FEDER-007038).

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