The development of a drug delivery system (DDS) is essential to remedy the limitations of free drug molecules. The use of silica as a DDS over other systems (for example, liposomes) can be attributed to it being more robust and versatile. This thesis investigates bio-inspired silica (BIS) and compares it to mesoporous silica nanoparticles (MSN), which have received much attention for drug delivery applications. The BIS synthesis utilised amines to condense silica quicker than MSN, under benign conditions and without the use of hazardous chemicals. With this synthesis method drugs can be loaded in situ and there is potential for amines to have dual function of condensing silica and acting as functionalisation. BIS has also been shown to be more biocompatible than MSN. Due to these reasons it can be argued that BIS has the potential to be a more desirable silica DDS than MSN.Using ibuprofen as a model drug, reaction conditions (e.g. choice of amine additive, synthesis pH and maturation time) were systematically investigated to elucidate their effects upon drug loading and release. BIS synthesised with the amine poly(allylamine hydrochloride) (PAH) (which will henceforth referred to as BIS-PAH) was focused on, as this was the only amine system which released a significant proportion of loaded drug and achieved comparable or improved ibuprofen loading when compared to MCM-41. PAH plays an important role in facilitating the loading of ibuprofen, however if too much is present, release is inhibited greatly. The condensation rate of silica is also an important factor; when condensation rate was increased more drug was able to be released. This is likely due to less of the drug being entrapped within the silica particle and more being phys-adsorbed to the silica surface. Next the use of BIS to deliver hydrocortisone (HC) was investigated.Current treatments for adrenocorticoid insufficiency using hydrocortisone do no mimic the natural circadian variation in levels of blood cortisol. Firstly, the stability of HC during the in situ loading process was measured and data are presented that show that HC must be loaded post-synthesis, to avoid degradation in the reaction mixture. The efficiency of loading was largely unaffected by amine, however, only BIS-PAH allowed for drug release. Longer BIS-PAH maturation times gave lowered loading but the release was improved.Finally, biocompatibility of BIS was also investigated and it was found that, BIS was able to pass through the gut wall into the blood stream, and it was non-haemolytic when compared to MCM-41. There is a potential for bioaccumulation due to silica’s chemical stability.Although the use of BIS for delivery of hydrocortisone was unsuccessful, BIS does have several advantages over MCM-41 (such as quicker synthesis route, involving a one-pot synthesis and drug loading method, simple controllability, lack of hazardous chemicals and superior biocompatibility) and the results presented here show that BIS has similar or improved drug loading and release profiles to MCM-41 when using ibuprofen. With further drug and biocompatibility experiments, these benefits give BIS real potential as a viable DDS to be further investigated.
|Date of Award||17 Dec 2016|
- University Of Strathclyde
|Sponsors||EPSRC (Engineering and Physical Sciences Research Council)|
|Supervisor||Izabela Cebula (Supervisor) & Mary Grant (Supervisor)|