Monodisperse Mesoporous Amphiphilic and T-Group Micron Size Silica Particles

Abstract

Organosilica particles of a narrow size distribution made from differentsiloxanes (VTMS,PTMS and MerTMS), were prepared by means of a one-stepsynthesis. In a one-step synthesis, vinyl, phenyl and 3-mercapto-functionalizedsilica particles with a range of 1.2 to 4.7 µm were synthesized by hydrolysisand condensation using the semi-batch process. The particles are alwaysmonodisperse apart from phenyl-functionalized silica particles. Reactionparameters by means the amount of silane, additives (hexane, toluene,mesitylene, n-tridecane), stirringspeed and dosing rate were systematically investigated and discussed withrespect to the target variables particle size, particle size distribution,particle morphology and porosity. All main factors as well as the additivesdosing rate interaction have a significant influence on the particle size,shape and morphology.Porous microspheres are often used for drugdelivery. However, systems for simultaneous delivery of multiple drugs arescarce. Here anisotropic and amphiphilic dumbbell core-shell silica particleswere prepared by a simple etching process that can load and release two drugs.The dumbbells consisted of large dense lobes and smaller hollow hemispheresboth with shells of mesoporous channels as revealed by electron microscopy. Theproperly adjusted stirring speed and the application of ammonium fluoride as an etching agent determined the shape and the surface anisotropy of the particles.In particular, the surface of the dense lobe and the small hemisphere differedin their zeta potentials as confirmed by drug loading experiments. ConfocalRaman microscopy and spectroscopy showed that the two polyphenols curcumin(Cur) and quercetin (QT) accumulated in different compartments of theamphiphilic particles. The overall drug loading efficiency of Cur plus QT washigh for the amphiphilic particles but differed widely between Cur and QTcompared to controls of core-shell silica microspheres and uniformly chargeddumbbell microparticles made by using ammonium carbonate as an etching agent. Forthe amphiphilic particles, we found up to 98 % drug loading and 100 % releaseefficiency after 6 h at pH 5.5. Furthermore, Cur and QT loaded microparticlesshowed different cancer cell inhibitory activities. The highest activity wasdetected for the dual drug loaded amphiphilic microparticles (IC50 13.5 nM) incomparison to the controls. In thelongterm, amphiphilic microparticles are promising carriers for thesimultaneous delivery of multiple drugs.