Antibakteriyel Aljinat Mikrobaloncuk Yapıların Mikroakışkan Sistemle Hazırlanması

Abstract

Microbubbles produced with microfluidic systems have been used as contrast agents in ultrasound radiography for approximately 30 years. In recent years, it has been successfully used in different biomedical applications due to its simple, fast and reproducible production possibilities. These applications include drug delivery systems, gene therapy, intravenous oxygen transport agents, cancer therapy, blood-brain barrier targeted drug carriers, thrombolysis and focused ultrasound imaging. Microbubbles are also used in the production of scaffolds with homogeneous pore distribution. Pore size, homogeneity and architecture can not be fully controlled in structures produced by traditional methods such as freeze drying, phase separation, gas foaming, particle removal or use of porogen. In microfluidic systems, on the other hand, since a continuous flow production takes place, the microbubbles are stable, homogeneous and have a narrow pore size range. In this thesis, it was aimed to produce alginate/poly(vinyl alcohol)/polyethyleneimine (Alg-PVA-PEI) microbubbles using T-junction microfluidic system, and to prepare porous structures with antibacterial properties by supplementing these structures with iv silver nanoparticles (AgNP). For this purpose, Alg-PVA-PEI microbubbles were produced with T-junction microfluidic system and system parameters were optimized. By keeping the constant flow rate of 200 μL/min and the gas pressure of 9L/min in the system, microbubbles in the size range of 90-175 μm were obtained depending on the ratio of PEI and AgNP in polymer solution. On the other hand, AgNPs were synthesized to give antibacterial properties to these structures. Average diameter of AgNPs was 31.63±3.7nm, PDI value was 0.11 and surface charge zeta potential value was -21.7±9.1 mV. Antibacterial microbubbles (Alg-PVA-PEI/AgNP) were produced by adding the synthesized AgNPs to the Alg-PVA-PEI solution. Microbubble structures with high water retention capacity, extended silver nanoparticles release profile, non-toxic and antibacterial properties were obtained when microbubbles were cross-linked with calcium chloride (CaCl2). The water retention capacity of the microbubble structures were found to be between 3685-4300 %. The release profiles of AgNPs from alginate microbubble structures were examined and it was observed that AgNPs exhibited a burst release in the first 24 hours due to the highly hydrophilic natura of the microbuble structure and then release was extended up to 7 days. While microbubble structures containing 0.05% AgNP and 1% PEI showed 105% cell viability and 2605 ppb AgNP release after 72 hours. It was observed that the amount of AgNP above this value adversely affected cell viability. According to the disk diffusion test results, microbubble structures containing Alg-PVA did not show antibacterial effect, whereas microbubble structures containing PEI and AgNP exhibited high antibacterial properties against gram-negative Escherichia coli (E. coli–ATCC 25922) and gram-positive Staphylococcus aureus (S. aureus-ATCC 29213), ATCC Methicillin Resistant Staphylococcus aureus (MRSA) bacterial strains. As a result, it was concluded that PEI and AgNP containing microbubble structures could be a good wound dressing candidate for infected and highly exuding wounds, considering their long-term antibacterial activity, high water retention capacity, cellular compatibility.