A simple and effective means for obtaining hollow silica particles of controlled diameter from about 60 to 120 nm is presented. The synthesis utilizes equilibrium vesicles as templates for the directed growth of silica. Two different surfactant systems are used to form the vesicular templates: (a) mixtures of cetyltrimethylammonium bromide (CTAB) and sodium perfluorooctanoate (FC7) and (b) mixtures of cetyltrimethylammonium tosylate (CTAT) and sodium dodecylbenzenesulfonate (SDBS). These templates were chosen because these mixtures of surfactants in water form unilamellar vesicles spontaneously that appear stable in the chemical environment required for silica synthesis. Tetramethoxysilane (TMOS) is added to the vesicular templates as a precursor for silica formation via acid-catalyzed hydrolysis and polycondensation. The morphology of the silica products as observed with transmission electron microscopy (TEM), quasi-elastic light scattering (QLS), and small-angle neutron scattering (SANS) is consistent with silica deposition at the vesicle surface, creating hollow silica particles with a 1-2-nm-thick shell and with a core diameter identical to that of the template. TEM reveals under different conditions either discrete hollow particles or networks of linked or aggregated hollow silica shells.

Hollow polymer spheres of styrene and divinyl benzene can be templated from catanionic equilibrium vesicles formed by cetyltrimethylammonium tosylate (CTAT) and sodium dodecylbenzenesulfonate (SDBS) or cetyltrimethylammonium bromide (CTAB) and sodium octyl sulfate (SOS). Characterization by many methods suggests the microstructure of the equilibrium vesicle template is left largely intact in the final polymer product. The particles have an average radius of ca. 60 nm and a membrane shell less than 10 nm thick. The cross-linked hollow polymer vesicles are robust and withstand complete drying and resuspension in water with no apparent change in microstructure. The polymer membrane surfaces can be functionalized by sulfonation or surfactant adsorption, and this functionalization prevents aggregation of the polymer particles when they are resuspended in water.

Intestinal mucus provides a significant barrier to transport of orally delivered drug carriers, as well as other particulates (e.g., food, microbes). The relative significance of particle size, surface chemistry, and dosing medium to mucus barrier properties is not well characterized but important in design of delivery systems targeted to the intestinal mucosa. In this study, multiple particle tracking (MPT) was used to study diffusion of 20- to 500-nm diameter carboxylate- and polyethylene glycol- (PEG-) functionalized polystyrene model carriers through intestinal mucus. The impact of exposure to mucus in buffer vs. a partially digested triglyceride mixture was explored. Effective diffusivity of particles in intestinal mucus decreased with increasing particle size less than and more than theoretically (Stokes-Einstein) expected in a homogenous medium when dosed in buffer and model fed state intestinal contents, respectively. For example, effective diffusivity decreased 2.9- vs. 20-fold with increase in particle size from 100 to 500 nm when dosed to mucus in buffer vs. lipid-containing medium. Functionalization with PEG dramatically decreased sensitivity to lipids in dosing medium. The results indicate that reduction of particle size may increase particle transport through intestinal mucus barriers, but these effects are strongly dependent on intestinal contents and particle surface chemistry.

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