Development of Nanomaterials for drug delivery and protein binding

Abstract Graphene oxide (GO) and dendrimers were investigated as ligands for protein binding and drug delivery in this thesis. Amino acids were used to modify protein binding and recognition, exploiting the architecture of these materials. Firstly,functionalized GO was synthesized with amino acids, creating a monomeric and oligomeric GO surface with functional groups. The effects of functionalization on GO binding to Chy were examined, and the results showed that glutamic oligomeric inhibited binding more than the monomeric system or unfunctionalized GO. Competitive inhibition was observed in all cases. The next area of study focused on dynamic combinatorial libraries for selecting the optimal dendrimer for a given protein. This involved creating dendrimers and thioester-terminated amino acids, followed by introducing the target protein into a solution containing a library of variously sized dendrimers and functionalized amino acids as part of a dynamic combinatorial selection procedure. The final area of investigation cantered around non-covalent modification of dendrimers. Dendrimers are increasingly popular for delivering hydrophobic and poorly soluble molecules to specific locations. They can host small guest molecules within their internal space, particularly high-generational dendrimers with secondary interactions. However, dendrimers' practical application is limited due to high cost and synthesis time. Hyperbranched polymers (HBP), simpler and more cost-effective alternatives, could be used if they yield comparable results. This study aimed to explore the encapsulation capabilities of various HBPs in conjunction with dendrimers to improve drug delivery efficacy. The researcher synthesized neutral PAMAM dendrimers for encapsulation investigations, focusing on three generations (G4.0-OH, G3.0-OH, and G2.0-OH). The study found that G3.0- OH exhibited the most effective drug encapsulation. However, HBPAMAM could not be converted into hydroxyl terminal groups. The study observed a decrease in the molecular weight 8 of HBPAMAM as reaction time increased, levelling off after thirty minutes. The monomeric molar ratio between EDA and MBA did not affect HBPAMAM's molecular weight. Encapsulation experiments were conducted on both HBPs. HBPAMAM-NH2, with amine terminal groups, improved the solubility of ibuprofen at low and high concentrations, but as polymer concentration increased, the encapsulated drug concentration decreased. Dynamic light scattering (DLS) showed that polymer size increased with concentration, and above 0.04 mg/mL, the polymer began to cluster. Dendrimers were more effective than HBPs at increasing ibuprofen concentration, but HBPs were not significantly less effective at drug encapsulation. At a concentration of 0.75 mg/mL, there was no significant difference between the amine-terminated PAMAM dendrimer G3 and the amine-terminated HBPAMAM in drug encapsulation. At a concentration of 0.32 mg/mL, HBPAMAM-NH2 encapsulated substantially more ibuprofen than the G2 dendrimer.