Novel pH-responsive hybrid peptide block copolymers for intracellular delivery applications
Leung, Angela Mu Hsien
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The creation of novel polymeric materials remains a vital field, particularly for potential applications in drug and gene delivery. The synthesis of these materials is important, as well as a clear understanding of the physical properties. Lastly, tests for potential applications are vital in order to improve and optimize the polymeric system. The polyglutamate-b-poly(N,N-diethylaminoethyl methacrylate) (PLG-b-PDEAEMA) block copolymer was successfully synthesized. The resulting polymer had a defined molecular weight with approximately 18 L-glutamate and 38 DEAEMA units and a low polydispersity index. The physical properties of the PLG-b-PDEAEMA block copolymer were investigated. As a result of the pH-sensitive groups of the polymer, the solution characteristics changed depending on the charge density of the individual blocks. At low pH, the PDEAEMA block is soluble and positively charged while the PLG block is insoluble. At high pH, the PLG block is negatively charged and hydrophilic, while the PDEAEMA block is hydrophobic. At mid-range pH values, the polymer chain is partially charge with both positive and negative moieties. The critical micelle concentration, size of the self-assembled structures, surface charge and morphology were found to change with pH. In order to investigate the potential applications of the PLG-b-PDEAEMA polymer, the interactions between the polymer and plasmid DNA were investigated. The delivery of the polymer/DNA polyplexes to a cell culture was investigated, however, no cell transfection was observed. Another aspect of the project was to understand the physical properties of poly(L-glutamate) dendritic polymers. Well-defined poly(L-glutamate) arborescent polymers from linear to G3 were characterized for their acid-base characteristics and aggregation behaviour at high solution pH. The Gibbs free energy required to abstract a proton was studied using potentiometric titration and it was found that both the pKa and the free energy increased at higher generations due to greater electrostatic forces. As a result of the hydrophilic glutamate groups and the hydrophobic hexyl group, the dendritic polymers aggregated to form self-assembled structures. The structures possessed similar hydrodynamic radii, ranging from 90 to 110 nm. The radius of gyration, in comparison, deceased from 90 to 30 nm with increasing polymer generations, indicating more core-dense aggregates at higher generations.