Openbare doctoraatsverdediging Katarina jokicevic 12/01/2021 - Spray-dried formulation development of novel upper respiratory tract lactobacilli - Departement Farmaceutische Wetenschappen

Promotoren: Professor Filip Kiekens en professor Sarah Lebeer

With the discovery of penicillin a revolution in chemotherapy and medicine, modern ‘antibiotic era’, has started and lives of millions of people have been saved from death and suffering caused by bacterial infections. However, the overuse of antibiotics within and outside the healthcare sector has led to an emerging, big threat to the well-being of the humankind called the antimicrobial resistance (AMR). The upper respiratory tract (URT) is the main entrance point for many viral and bacterial pathogens, and URT infections are among the most common infections in the world followed by high and often unjustified antibiotic use. Recent evidences imply the importance of lactobacilli as gatekeepers of a healthy URT. However, the benefits of putting health-promoting microbes or potential probiotics, such as these URT lactobacilli, in function of URT disease control and prevention is underestimated, among others because of the absence of adequate formulation modalities.

Probiotics are ‘live microorganisms that, when administered in adequate amounts, confer a health benefit on the host’ (Hill et al. 2014). The incorporation of probiotics into pharmaceutical formulations or functional foods is very challenging. Key problems in the development are maintaining high viability including long-term stability (preferably measured in years), functionality of probiotic cultures, quality and process monitoring and an adequate demonstration of positive benefit-risk ratios. Drying, i.e. lowering water content, is a common strategy used to enhance the short shelf-life of beneficial bacteria. Nevertheless, drying is linked with another set of challenges, such as dehydration, heat or cold stress, osmotic stresses, mechanical stresses, significantly impacting cell viability and functionality. Spray drying is a fast, continuous, cost-effective method with end product being powder with tunable characteristics. Yet, it is an underexplored alternative to the conventional freeze drying method of probiotic preservation due to high process temperatures and insufficient literature data on storage stability, functionality and application feasibility of spray-dried cultures.

Therefore, the goal of this project was to investigate the potential of spray drying for production of viable, functional and long-term stable URT (potential) probiotics. Key process characteristics exhibiting most significant damaging effects on bacterial cells were unravelled and minimised. Different protection strategies were envisaged resulting in high viability both after spray drying and storage (over a year). Novel probiotic nasal sprays and oral powders with uncompromised cell functionality have been developed. In vitro and in vivo testing including human volunteer study confirmed the effectiveness of developed probiotic formulations and the validity of postulated principles.

Finally, it can be concluded that the age of probiotics is yet to come and this research paves the way to new treatment opportunities to ease the battle against URT and other microbial-based diseases and fast-evolving AMR.