| Summary: | Synthetic mesoporous silica is a versatile and popular material widely utilized in drug delivery. Although, synthetic mesoporous silica are able to be synthesized with various morphologies, sizes and properties that can be altered for various applications, their synthesis is not only expensive and time-consuming but it also requires the usage of high energy and toxic materials. The production of synthetic mesoporous silica at a large-scale is not sustainable and commercially feasible. Therefore in order to address these disadvantages, there is a need to explore alternative silica porous materials as a suitable delivery platform. In this project, we studied the usage of natural silica-based porous material derived from diatoms known as diatomaceous earth (DE) as a delivery platform for nitric oxide (NO).
In this work, we first repurposed DE into a nitric oxide donor, S-nitrosothiols. Secondly, we optimized the synthesis process of DE through (i) improvement of the production yield of thiol-functionalized DE after surface functionalization; (ii) optimization of the concentration of sulfhydryl groups prior to NO loading by varying the volume of 3-Mercaptopropyltrimethoxysilane (MPTMS) and the reaction time after the addition of MPTMS. Thirdly, the NO-loaded DE particles were encapsulated into alginate beads to prolong the release rate of nitric oxide. Lastly, the effects of nitric oxide released from encapsulated NO-loaded DE alginate beads on angiogenesis was examined in this study.
The results obtained from this study had shown that the production yield of thiol- functionalized DE was improved after scaling up without sacrificing the NO loading efficiency. Introducing an additional alginate gel network to encapsulate the NO- loaded DE particles was proven in this investigation to be capable of prolonging the release of nitric oxide. Cytotoxicity assay conducted had shown a high cell viability of 92% and 87% when 0.015g of encapsulated NO-loaded DE alginate beads was added to human dermal fibroblasts (HDF) and human umbilical vein endothelial cell (HUVEC) respectively. These results proved that encapsulated NO-loaded DE alginate beads posed a low cytotoxicity risk.
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