Design and nanomedicine applications of atmospheric cold plasma functionalized nano and micro-sized drug delivery systems

In recent years, the development of drug delivery systems has become a significant research area in biotechnology, materials science, and the pharmaceutical industry. Drug delivery systems aim to enhance the effectiveness of drug therapy by offering advantages such as targeted drug delivery, achieving the desired duration of effect, and reducing side effects. Therefore, the design and development of next-generation carrier systems have become an important necessity. The primary aim of this thesis is to develop functionalized quercetin-loaded graphene oxide nanoparticle-based and PCL nanofiber, PCL/GO composite drug delivery systems using the atmospheric pressure cold plasma method. The study consists of three main stages. In the first stage, graphene oxide (GO) was synthesized from graphite and modified with atmospheric pressure cold plasma (APCP) for different durations (0, 1.5, 10 minutes). The purpose of this modification is to improve the surface properties and biological compatibility of GO. In the second stage, polycaprolactone (PCL)-based drug delivery systems were developed. During this process, PCL and quercetin (QU) containing PCL/QU solutions were modified with APCP for 0, 0.5, 1, and 3 minutes before electrospinning. The effects of plasma modification on the surface morphology and drug loading capacity of PCL were examined in detail. In the final stage, the GO and modified GO developed in the first stage were blended with PCL to develop PCL/GO-based composite nanofiber drug delivery systems. The controlled release and biocompatibility properties of quercetin in these composite structures were investigated. The effectiveness of these developed systems was tested using the MDA-MB-231 breast cancer cell line. Structural and morphological analyses were performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Physicochemical properties were examined using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Drug release profiles were evaluated using UV-Vis spectroscopy, and release kinetics were calculated. Cell proliferation and apoptosis tests were carried out using flow cytometry. The modification of PCL solutions with the APCP process before electrospinning shows a significant impact on the resulting nanofiber drug delivery systems. Before electrospinning, PCL solutions were subjected to the APCP process for 0.5, 1, and 3 minutes. The duration of the APCP process affects the morphology and size of the nanofibers, with longer durations resulting in larger fibers. The addition of QU reduces fiber diameter while offering opportunities to control and modify the properties of the drug delivery systems. The APCP process ensures the integrity of the polymer structure by preventing unwanted chemical changes or degradation of PCL nanofibers during electrospinning. XRD results confirm the stability of PCL nanofibers under APCP conditions. The APCP process also affects nanofiber hydrophobicity, with shorter durations increasing hydrophilicity. QU release percentages vary according to the duration of the APCP process, with PCL/CAP-0.5-QU standing out with the highest release percentage (56±2.2%), surpassing unmodified PCL/QU. Additionally, the combination of QU and the APCP process synergistically reduces cancer cell viability, increases QU release, and enhances drug loading efficiency, making it a promising approach for drug delivery system applications.