• The Hospital Research Foundation Mid Career Fellowship: Trojan Horse strategies for the smart delivery of antimicrobial bioactives

More than 99% of the total bacterial biomass exists as surface-attached agglomerates that are enveloped in a complex self-produced matrix, collectively known as biofilm. The biofilm provides protection from environmental insults, including host immune defense and antibiotic therapy. Once established, biofilms are responsible for serious and persistent chronic bacterial infections (e.g. osteomyelitis, wound infections, cystic fibrosis, chronic sinusitis).

Bioactives such as enzymes and peptides have transformed medical science and improved patient outcomes dramatically, e.g. in cancer therapy. However, these molecules are still underutilised in the treatment of infectious diseases. Antimicrobial enzymes and peptides offer unparalleled opportunities to treat recurring infectious diseases by disrupting biofilms that encase and protect resistant pathogenic bacteria. This clears the way for (previously ineffective) antibiotics that can now eradicate the infection when co-administered with the bioactives.

Our research group systematically designs, characterises, optimises and preclinically evaluates Trojan Horse strategies for the smart delivery of antimicrobial bioactives. Concealing and protecting bioactives from premature degradation, the developed Trojan Horse carriers “sense” the presence of an infection and respond by releasing their payload for most effective and direct antimicrobial effect at the site of infection, e.g. infected wounds. 

• Oral Drug Delivery of Poorly Water-Soluble Drugs

Up to 70% of all drugs developed in drug discovery programs are associated with poor water solubility causing erratic drug absorption in the intestinal tract. Importantly, when taken together with a meal, poorly water-soluble compounds may show toxic side-effects due to the substantially improved drug absorption facilitated by some food components (particular lipids). Lipid-based formulations such as self-nanoemulsifying drug delivery systems (SNEDDS) can overcome the solubility limitations of poorly water-soluble drugs resulting in reliable drug absorption independent from food intake. Lipid-based delivery systems are usually liquid but can be solidified by adsorption to porous carriers (e.g. silica). Our group uses advanced characterisation methods including in vitro digestion, solid state analysis and in vivo models (dogs and pigs, rats) to develop and characterise lipid-based drug delivery systems that are capable to deliver modern and safe medicine to the community.