Bioactive glass nanoparticles for therapeutic applications

Abstract

There is great therapeutic potential for bioactive glass nanoparticles, as they can be internalised within cells and achieve sustained intracellular delivery of active ions. Bioactive glass nanoparticles are also used in nano-composites. The Stӧber process is commonly used for synthesising spherical silica particles. This thesis reports a comprehensive study of how the process variables can be systematically altered to obtain monodispersed particles of specific sizes in the range 20 – 500 nm. Modification of the Stӧber process so that the particles can contain cations such as calcium, which can impart bioactivity, while maintaining monodispersity, is therefore highly desirable. Here, both zinc and calcium incorporation is achieved, with a homogenous distribution and without affecting the size, dispersity or morphology of the particles. However, careful characterisation shows that much of the cations were not incorporated and a washing step was essential, which suggests that previous reports are likely to have overestimated the amount of calcium incorporated. A maximum of 8.9 ± 1.1 mol % CaO and 22.7 ± 0.8 mol % ZnO was incorporated into the particles. Monodispersed mesoporous silica particles were also synthesised in this thesis, containing up to 18.5 ± 2.7 mol % Ca and 21.5 ± 1.3 mol % Zn. The differences in incorporation between the two cations were attributed to the different roles that they play within the silicate network. Whilst calcium acts purely as a network modifier, zinc can also act as a network former. These differences are seen to affect % cation incorporation, surface area, network connectivity and subsequent degradation. Nanoparticles of 80 - 100 nm were readily internalised by cells, where they were located both within vesicles and also as individual particles within the cytoplasm (having escaped from the endosomal pathway). SiO2-ZnO mesoporous particles were also seen to subsequently degrade rapidly inside cells, demonstrating preferential toxicity to cancer cells due to pH sensitive intracellular release of toxic Zn2+ ions. SiO2-CaO particles were successfully functionalised and show great potential for incorporation into nano-composites for bone regeneration.