Synthesis and characterisation of targeted delivery systems containing phosphoester bonds in nanobiotechnology

Within the scope of this thesis study, in order to develop new, smart polymeric nanoparticle systems that can be used for nanobiotechnological applications, the synthesis and characterization of functional polymers containing phosphoester bonds in their structure, preparation of nanoparticle formulations and their effects on cell viability were examined by in vitro cytotoxicity test. Within this scope, two groups of polymers containing phosphoester bonds were synthesized. In the first group, a new polymer that was not found in the sources was synthesized by modification of Poly(acrylic acid) (PAA), which is widely and safely used as drug delivery systems. As the second polymer group, poly(ß-aminoester) (PBAE), which has been considered important as biocompatible drug/gene carrier nanoparticle systems in recent years, was synthesized by polycondensation proceeding according to the Michael addition reaction. Both synthesized polymers have a polyampholyte structure that contains both anionic and cationic groups together. The characterization of the synthesized polymers was carried out by Fourier Transform Infrared Spectroscopy (FTIR) and Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) analyses. The nanoparticles of PAA-based products were prepared by ionic gelation, and nanoparticles of PBAE product were prepared by nanoprecipitation method. The Proton buffering capacity and isoelectric points of the polymers were determined. In the optimization study of polymeric nanoparticulate systems; the size, polydispersity index (PDI) and zeta potential properties of those systems accepted as drug carriers were taken into consideration. The pH-dependent changes of these properties were examined and the colloidal stability of the prepared nanoformulations was monitored. The effect of optimum nanoparticle formulations on cell viability was examined on human embryonic kidney (HEK 293) and/or primary sheep fibroblast (POF) cell lines, and finally, both groups of polymers were modified with Folic acid (FA) in order to target cancer cells and FTIR analysis of the products. was carried out. As a result, it has been established that the modified PAA and PBAE polymeric nanoparticle systems prepared within the scope of this thesis study are suitable candidates as pH-sensitive, biocompatible and targetable drug carriers.