Large antibiotic molecule diffusion in confined mesoporous silica with controlled morphology

Abstract

Ordered mesoporous silica (OMS) having different pore geometries was confined in the channels of anodic alumina membranes (AAMs), as a model system, to investigate the adsorption and release of bioactive molecules. These systems allow us to isolate the parameters that play a role in the diffusion of molecules in the mesopores without the complications associated with different external morphologies and particle size. Three mesoporous systems were synthesized within the AAMs, i.e., systems (i) and (ii) with pore diameters of about 4 and 9 nm having a columnar alignment of mesopores, and system (iii) featuring a 7 nm pore system with a circular channel structure. The uptake and release of vancomycin, a large antibiotic molecule (3.2 × 2.2 nm) used in treating osteomyelitis, was studied in these model systems. Calcined samples before and after drug uptake were characterized by SAXS, nitrogen sorption, transmission electron microscopy, thermogravimetry and UV-Vis spectroscopy. It was found that columnar mesopores could easily adsorb vancomycin, in increasing amounts with larger mesopore size. In contrast, circular, hardly accessible channels did not allow any drug uptake. Drug delivery profiles were collected, aimed at investigating the first minutes of delivery and delivery behavior at longer time scales. It was found that the pore diameter played a minor role in the diffusion kinetics, while the pore morphology and the diffusional path lengths have profound effects on the release of the drug. Results obtained for these model systems are contrasted with the behavior of two SBA-15 host systems, synthesized in powder form and having spherical and fibrous morphologies. The spherical particles are accessible to the drug molecules, but they take up only a moderate amount of vancomycin based on available pore volume, due to the pore tortuosity and the pore diameter which is similar to that of the vancomycin molecules. In contrast, SBA-15 fibers showed no adsorption capacity towards vancomycin, due to the low accessibility of mesopores which are partially closed at the fiber ends.