Mesoporous Silica Particles for a Potential Therapeutic Application

Abstract: Mesoporous silica particles (MSPs) have a high surface area, pore volume, and tunable pore size and surface properties, which makes them ideal for advanced therapeutic, biocatalytic, separation, and drug delivery applications. The work in this thesis shows that MSPs can be employed for therapeutic applications with minimal risk of adverse consequences. The MSPs in the study are of the SBA-15 type.Obesity is a serious health problem caused by an excess of adipose tissue (body fat) as a result of inadequate energy expenditure. Both in developed and developing countries, the prevalence is increasing rapidly. Type 2 diabetes (T2D) mellitus is going to be one of the most destructive consequences of the global obesity pandemic. Obesity and diabetes are anticipated to affect 783 million people by 2045, with diabetes being the leading cause of death for an estimated 6.7 million people in 2021 (according to International Diabetes Federation, IDF Diabetes Atlas 10th edition, 2021). People who are overweight or have diabetes are more likely to trigger other physiological conditions such as the development of dyslipidemia. Dyslipidemia is defined by a combination of risk factors for cardiovascular disease, including excessive plasma free fatty acids, cholesterol, and triglycerides; low levels of high density lipoprotein (HDL); and aberrant low-density lipoprotein (LDL). Public health expenditures and initiatives are under severe strain as a result of these situations. Researching therapies that are both safe and effective is in dire need.MSPs were produced at bench scale, and scaled to pilot (100L) and then at a relatively large demonstration scale (100-1000L) and tested in vitro, in vivo, ex vivo, and clinically. The results from these studies have shown that when administered orally, MSPs adsorb enzymes that break down carbohydrates and lipids (amylase and lipase), physically separating them from their large substrates. When administered orally, this consequently reduces the breakdown of carbohydrates and fats, leading to a lowering of the total energy intake in animals and humans. This occurs when the MSP has pore sizes which is typically in the range of 8–13 nm that are slightly larger than the food-digesting enzymes. The research carried out as part of this thesis showed that when the MSPs are in the micron size range, they operate locally in the gastrointestinal tract (GIT) and exit in the fecal mass without being absorbed by the body. The adsorbed enzymes aid in the safe transit of MSPs through the gastrointestinal system. Furthermore, the presence of these digestive enzymes within the pores was shown to have no effect on enzymatic function. It was also observed that when a large substrate (starch) was used to measure the activity of α-amylase adsorbed in the pores of MSPs, the activity appeared reduced. However, this was not related to an inactivation of α-amylase but to the fact that starch was molecularly too large to enter the pores of the MSPs.