Design and Development of Novel Nanocarriers for Targeted Drug Delivery

In this thesis, several nanoformulations have been prepared using different combinations of biomaterials including silk fibroin, sodium alginate, lipids, and amphiphilic cationic peptides as drug delivery systems. The physiochemical properties of these formulations were characterized and their efficiency as drug delivery systems was evaluated in vitro including 2D and 3D cell culture. ASC-J9 has been selected as a hydrophobic small molecule anticancer model drug that requires nanocarriers to modify its kinetics, prolong its circulation time and improve its activity. The designed nanocarriers successfully encapsulated ASC-J9, modify its release and enhanced cellular uptake. In the first experimental chapter, the particle elasticity theory was investigated by preparing stiffness-tunable nanoformulation. One of the main limitations in large scale production of nanomaterials is batch to batch variation and lack of controllability during processing. To address these limitations a newly designed microfluidic mixer was introduced (swirl mixer) and its performance was assessed in comparison to conventional microfluidic designs. In the last experimental chapter, magnetic silk nanoparticles were manufactured and functionalised with G(IIKK)3I-NH2 amphiphilic cationic anticancer peptide. These functionalised nanoparticles not only improve the delivery of ASC-J9 but also demonstrated an augmented anticancer activity. Overall, the data presented in this thesis contributes to the field of nanomedicine and introduces new preparation techniques for the pharmaceutical industry and potential nanoformulations for cancer therapy.