Sonochemical Development of Magnetic Nanoporous Therapeutic Systems as Carriers for 5-Fluorouracil Pages 26-35

Alina Maria Tomoiaga1,2, Lacramioara Ochiuz3 and Aurelia Vasile1

1Department of Chemistry, “Alexandru Ioan Cuza” University of Iasi, 11, Carol I bd., Iasi, 700506, Romania; 2Research Department, ChemPerformance Ltd., 37, Fintinilor Street, Iasi, 700337, Romania; 3Department of Pharmaceutical Technology, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, 16, Universitatii Street, Iasi, 700115, Romania



Abstract: Therapeutic nanosystems based on magnetic mesoporous silica nanoparticles are successfully obtained by a facile, reproducible and time-saving sonochemical method. Hydrophilic citrate-capped magnetite nanoparticles of about 20 nm are firstly prepared by ultrasound-assisted chemical precipitation. Secondly, freshly-dried magnetite nanoparticles are coated with mesoporous silica shell by sonochemically-modified Ströber method. The applied procedure provides easily-separable, stable core-shell nanoparticles consisting of superparamagnetic Fe3O4 cores and mesoporous silica shell. SEM micrographs showed that core-shell nanoparticles are smaller than 400 nm, a prerequisite for biomedical applications by intravenous administrations. Further, these sonochemically prepared magnetic nanoparticles are employed as biocompatible matrices to host and deliver 5-fluorouracil, a highly-toxic low-molecular antimetabolite chemotherapeutic drug. For this, drug molecules are confined into unmodified and amino-modified mesopores of the silica shell by adsorption from alcoholic solutions. A detailed study was performed using XRD, N2-sorption measurements, SEM and FTIR spectroscopy with the primary goal of investigating possible structural, textural and morphological modifications aroused after pore-functionalization and drug nanoconfinement. Magnetic behavior of prepared therapeutic nanosystems is visualized using vibrating sample magnetometry (VSM). Finally, the release profile of 5-fluorouracil from the unmodified and amino-modified nanoparticulate magnetic matrices in PBS solution (pH 7.4) is followed by means of liquid chromatographic measurements. The HPLC method used for determination of 5-fluoruracil in releasing media was fully validated in house, in terms of specificity, linearity, precision, LOD and LOQ establishment.

Keywords: Chemotherapeutic agents, drug nanoconfinement, controlled release, 5-fluorouracil, magnetic mesoporous silica, targeted delivery, ultrasonic irradiation.