Highly porous phosphate-based glasses for controlled delivery of antibacterial Cu ions prepared via sol-gel chemistry

Abstract

Mesoporous glasses are a promising class of bioresorbable biomaterials characterized by high surface area and extended porosity in the range of 2 to 50 nm. These peculiar properties make them ideal materials for the controlled release of therapeutic ions and molecules. Whilst mesoporous silicate-based glasses (MSG) have been widely investigated, much less work has been done on mesoporous phosphate-based glasses (MPG). In the present study, MPG in the P₂O₅-CaO-Na₂O system, undoped and doped with 1, 3, and 5 mol% of Cu ions were synthesized via a combination of the sol-gel method and supramolecular templating. The non-ionic triblock copolymer Pluronic P123 was used as a templating agent. The porous structure was studied via a combination of Scanning Electron Microscopy (SEM), Small-Angle X-ray Scattering (SAXS), and N₂ adsorption-desorption analysis at 77 K. The structure of the phosphate network was investigated via solid state ³¹P Magic Angle Spinning Nuclear Magnetic Resonance (³¹P MAS-NMR) and Fourier Transform Infrared (FTIR) spectroscopy. Degradation studies, performed in water via Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), showed that phosphates, Ca²⁺, Na⁺ and Cu ions are released in a controlled manner over a 7 days period. The controlled release of Cu, proportional to the copper loading, imbues antibacterial properties to MPG. A significant statistical reduction of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacterial viability was observed over a 3 days period. E. coli appeared to be more resistant than S. aureus to the antibacterial effect of copper. This study shows that copper doped MPG have great potential as bioresorbable materials for controlled delivery of antibacterial ions.

Fig. 1. Flow diagram of the sol–gel method used for the synthesis of Cu-doped MPG.

Fig. 2. XRD patterns of (a) MPG-und, (b) MPG-Cu1, (c) MPG-Cu3, and (d) MPG-Cu5.

Fig. 3. SEM images of (A) MPG-und, (B) MPG-Cu1, (C) MPG-Cu3, and (D) MPG-Cu5.

Fig. 4. SEM images of MPG-Cu3.

Fig. 5. Experimental SAXS data (lines) and fits (symbols) for (a) MPG-und, (b) MPG-Cu1, (c) MPG-Cu3, and (d) MPG-Cu5.

Fig. 6. N₂ adsorption and desorption isotherms at 77 K of (a) MPG-und, (b) MPG-Cu1, (c) MPG-Cu3, and (d) MPG-Cu5.

Fig. 7. ³¹P MAS NMR spectra of (a) MPG-und, (b) MPG-Cu1, (c) MPG-Cu3, and (d) MPG-Cu5. * = spinning sidebands.

Fig. 8. FTIR spectra of (a) MPG-und, (b) MPG-Cu1, (c) MPG-Cu3, and (d) MPG-Cu5.

Fig. 9. Release of (A) phosphate (ppm P), (B) calcium, (C) sodium and (D) copper ions in deionised water up to 7 days by ICP-OES. Error bars are standard deviation (n = 3).

Fig. 10. Antibacterial activity of all MPG doped with 1, 3, and 5 mol% of Cu against S. aureus NCTC 8325 (A) and E. coli K12 (B). ** = p ≤ 0.01, *** = p ≤ 0.001 **** = p < 0.0001.

Fig. 11. Variation of ³¹P isotropic chemical shifts of Qⁿ species with Cu loading in the studied MPG.