Studying the interactions between therapeutic peptides and absorption enhancers

Sammanfattning

Therapeutic peptides can often not be formulated as tablets by themselves as they’re prone to enzyme degradation the oral route - they also do not present good enough passage through epithelial cells to be viable for this dosage form. But if formulated together with surfactants, e.g., sodium caprate (C10), the absorption through epithelial cells can be increased. When peptides and absorption enhancers are mixed, their interactions can be important to be aware of. This is because unwanted aggregation of peptide could render the therapeutic useless or even dangerous to the patient. Knowing how the peptide affect the aggregation of the absorption enhancer can also be of importance, since different types of aggregates can increase absorption differently, and if the peptides can favour the aggregation of a certain type of structure, this can be useful to be aware of. This work has demonstrated at which different concentrations and environments C10 and salcaprozate (SNAC) forms different types of aggregates. This work has also indicated that a certain peptide, MEDI7219, might reduce the concentration at which micelles are formed by the formation of mixed micelles. Conformational changes for peptides when interacting with C10 was observed to be correlated with the peptide’s degree of lipidation. Further, this thesis has provided information that a ternary phase diagram for C10, capric acid and water largely contains capric acid crystals at room temperature and indicated that some changes in structure occur when heated to 37˚C. The equilibrium time for this system was also observed to be long, which could be useful knowledge in drug formulation. All results together indicate that there are hydrophobic interactions between MEDI7219 and C10, but more research is needed to determine at what extent their interplay affect both formulation stability and the therapeutic use of the peptides.