ENGINEERING PEPTIDE AMPHIPHILES FOR ENCAPSULATION OF HYDROPHOBIC SUBSTANCES

Abstract

Nearly 40% of the new chemical entities developed in the pharmaceutical industry are hydrophobic. Delivery of such hydrophobic drugs is challenging and methods were developed to improve their solubility. In this thesis, several design strategies were employed to explore the ability of peptide amphiphiles(PA) to serve as a carrier for hydrophobic drugs. Firstly, four collagen mimetic peptide amphiphiles(CMPA) containing aminoacids of varying degrees of hydrophobicity were tuned to form self-assembled nanofibers. Their ability to encapsulate hydrophobic drug was validated by harboring the hydrophobic model drug coumarin-6. Secondly, two CMPA with significant differences in hydrophobicity was utilised to determine the maximum threshold of encapsulation of antibacterial drug, chloramphenicol. Finally, hydrophobic anticancer drug camptothecin was encapsulated into two oppositely charged PA by co-assembly. Overall, the PA and hydrophobic drugs retained their secondary structure and bioactivity respectively after encapsulation. These strategies can be employed to advance into a lineage of smart peptide formulations.