Silane Modification of Mesoporous Materials for the Optimization of Antiviral Drug Adsorption and Release Capabilities in Vaginal Media

Abstract

Three different functionalities have been incorporated into mesoporous materials by means of a coupling reaction with the siloxanes 3-glycidoxypropyl-trimethoxysilane (GLYMO), 3-methacryloxypropyl-trimethoxysilane (MEMO), and 3-mercaptopropyl-trimethoxysilane (MPTMS). The disposition of the different functional groups, as well as the interaction mechanism, with the mesoporous substrate has been identified. The amount of the antiviral drug acyclovir (ACV) adsorbed depends not only on the available surface area but also on the chemical or physicochemical interactions between functionalities. The drug adsorption isotherm of the materials functionalized with GLYMO and MPTMS follow mechanisms dependent on the different surface coverage and the possibilities to establish physicochemical interactions between the drug molecule and the functionalities. On the contrary, when functionalizing with MEMO, the dominant adsorption mechanism is characteristic of chemically bonded adsorbates. The ACV release kinetics is best fitted to the Weibull model in all the functionalized materials. When the MTPMS is used as a functionalizing agent, the drug diffusion occurs at low kinetics and homogeneously along the mesoporous channels.

Keywords: acyclovir; antiviral; drug delivery; organic–inorganic hybrid.

Figure 1

Schematic representation of the synthesis of the mesoporous material, functionalization with the silane molecules, and the drug loading and release procedures.

Figure 2

Scanning electron microscope images of (a,b) mesoporous material (low and high resolution, respectively) and (c) the functionalized material containing 3% GLYMO.

Figure 3

Detailed regions of the FTIR spectrum of the mesoporous materials functionalized with (a,b) GLYMO, (c) MEMO, and (d) MPTMS silane at different concentrations.

Figure 4

(a) Relative intensity ratio of the bands centered at 1270 to 908 cm⁻¹ (left axis) and relative intensity of the band at about 1250 cm⁻¹ (right axis); (b) relative intensity ratio of the bands centered at 1723 to 1703 cm⁻¹ (left axis) and relative intensity of the band at about 1635 cm⁻¹ (right axis); (c) relative intensity ratios of the bands centered at 2570 to 2550 cm⁻¹. Lines are plotted to guide the eye.

Figure 5

Differential thermal analysis curves of the materials functionalized with (a) GLYMO, (b) MEMO, and (c) MPTMS at different concentrations (indicated in the labeling as % weight).

Figure 6

(a) Amount of coupling agent (in mmol) at each concentration of silane incorporated during the synthesis, and (b) combustion enthalpy of the silanes. Lines are plotted to guide the eye.

Figure 7

BJH pore distribution of the mesoporous hybrids functionalized with different percentage amounts of (a) GLYMO, (b) MEMO, and (c) MPTMS silane molecules at different concentrations (indicated in the labeling as % weight). Dash-dotted lines represent the BJH distribution of the unfunctionalized mesoporous hybrid particles.

Figure 8

Ceq (in mg/g) of the mesoporous materials functionalized with (a) GLYMO, (b) MEMO, and (c) MPTMS. Dotted line corresponds to the nonfunctionalized mesoporous material. Normalized absorption of ACV (in mmol/m²) with respect to the surface area of the materials functionalized with (d) GLYMO, (e) MEMO, and (f) MPTMS.

Figure 9

Release profiles of ACV in SVF functionalized with (a) GLYMO, (b) MEMO, and (c) MPTMS. Dotted line corresponds to the nonfunctionalized mesoporous material.

Figure 10

(a) Weibull kinetic parameter k (1/a) as a function of the silane concentration, and (b) Weibull transport parameter b as a function of the silane concentration.

Figure 11

FTIR spectra of the mesoporous materials loaded with ACV and functionalized with (a) GLYMO and (b) MEMO. Dotted lines show the FTIR spectra of the drug molecule ACV.