PURPOSE: To investigate the effect of surface functionalization of mesoporous silica nanoparticles (MSN) on crystallization, loading, release and activity of mitoxantrone (MTX). METHODS: Thiol-, amine-, and mixed thiol/amine-functionalized MSN were synthesized and characterized by electron microscopy, thermogravimetry, surface area analysis, elemental analysis and zeta potential. MTX loading and release kinetics were determined in phosphate and acetate buffers (pH 7.4 and 4.5). The crystalline state of MTX in MSN was determined by differential scanning calorimetry and X-ray diffraction. Cytotoxicity and activity of MTX loaded MSN were determined by MTS assay in MDA-MB-231 cells. RESULTS: Our results demonstrate that loading of MTX depends strongly on the type of surface functional groups in MSN. Thiol-MSN showed the highest MTX loading (18 % w/w) when compared with thiol/amine-MSN (6 % w/w) and amine-MSN (1 % w/w). MTX release was strongly dependent on the pH of the release medium and the type of surface functional group. MTX was found in the amorphous form when loaded in thiol-functionalized MSN. No significant effect of surface modification of MSN on particle toxicity was observed. MTX loaded in MSN exhibited comparable anticancer activity in vitro as free MTX. CONCLUSION: Surface modifications of MSN have significant effect on MTX crystallization and release behavior.
PURPOSE: To investigate the effect of surface functionalization of mesoporous silica nanoparticles (MSN) on crystallization, loading, release and activity of mitoxantrone (MTX). METHODS:Thiol-, amine-, and mixed thiol/amine-functionalized MSN were synthesized and characterized by electron microscopy, thermogravimetry, surface area analysis, elemental analysis and zeta potential. MTX loading and release kinetics were determined in phosphate and acetate buffers (pH 7.4 and 4.5). The crystalline state of MTX in MSN was determined by differential scanning calorimetry and X-ray diffraction. Cytotoxicity and activity of MTX loaded MSN were determined by MTS assay in MDA-MB-231 cells. RESULTS: Our results demonstrate that loading of MTX depends strongly on the type of surface functional groups in MSN. Thiol-MSN showed the highest MTX loading (18 % w/w) when compared with thiol/amine-MSN (6 % w/w) and amine-MSN (1 % w/w). MTX release was strongly dependent on the pH of the release medium and the type of surface functional group. MTX was found in the amorphous form when loaded in thiol-functionalized MSN. No significant effect of surface modification of MSN on particle toxicity was observed. MTX loaded in MSN exhibited comparable anticancer activity in vitro as free MTX. CONCLUSION: Surface modifications of MSN have significant effect on MTX crystallization and release behavior.
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