Tetracycline-Containing MCM-41 Mesoporous Silica Nanoparticles for the Treatment of Escherichia coli

Abstract

Tetracycline (TC) is a well-known broad spectrum antibiotic, which is effective against many Gram positive and Gram negative bacteria. Controlled release nanoparticle formulations of TC have been reported, and could be beneficial for application in the treatment of periodontitis and dental bone infections. Furthermore, TC-controlled transcriptional regulation systems (Tet-on and Tet-off) are useful for controlling transgene expression in vitro and in vivo for biomedical research purposes; controlled TC release systems could be useful here, as well. Mesoporous silica nanomaterials (MSNs) are widely studied for drug delivery applications; Mobile crystalline material 41 (MCM-41), a type of MSN, has a mesoporous structure with pores forming channels in a hexagonal fashion. We prepared 41 ± 4 and 406 ± 55 nm MCM-41 mesoporous silica nanoparticles and loaded TC for controlled dug release; TC content in the TC-MCM-41 nanoparticles was 18.7% and 17.7% w/w, respectively. Release of TC from TC-MCM-41 nanoparticles was then measured in phosphate-buffered saline (PBS), pH 7.2, at 37 °C over a period of 5 h. Most antibiotic was released from both over this observation period; however, the majority of TC was released over the first hour. Efficacy of the TC-MCM-41 nanoparticles was then shown to be superior to free TC against Escherichia coli (E. coli) in culture over a 24 h period, while blank nanoparticles had no effect.

Keywords: E. coli; MCM-41; controlled drug release; tetracycline.

Figure 1

TEM images of tetracycline-containing MCM-41 nanoparticles. (A) TC-MCM-41A (41 ± 4 nm) and (B) TC-MCM-41B (406 ± 55 nm).

Figure 2

UV-Vis spectra of tetracycline at 0 and 24 h. A slight downward shift in the spectra was observed at 24 h.

Figure 3

Adsorption of tetracycline (TC) by MCM-41A and MCM-41B. UV-Vis spectra of TC control at 24 h and TC not adsorbed by MCM-41A (green) and MCM-41B (light green). Percent drug adsorption was measured by comparing absorbance at 275 nm.

Figure 4

In vitro release of tetracycline from (A) TC-MCM-41A and (B) TC-MCM-41B, determined using UV-vis spectroscopy. Most drug was released by 5 h. All studies were carried out in PBS, pH 7.2, at 37 °C.

Figure 5

Survival (%) of E. coli treated by TC, MCM-41A, MCM-41B, TC-MCM-41A and TC-MCM-41B, determined using UV-vis spectroscopy. (A) TC concentration: 0.5 µg/mL and (B) TC concentration: 1.0 µg/mL. In each group, the concentration of free TC was the same as the concentration of TC in TC-MCM-41A and TC-MCM-41B, and concentrations of MCM-41A and MCM-41B corresponded to concentrations of TC-MCM-41A and TC-MCM41B, respectively.