Gümüş Nanoparçacıklarla ve Oksitetrasiklinle Modifiye Edilmiş Süper Emici Antibakteriyel Hidrojellerin Sentezi
Özet
New and effective antibacterial hydrogels with high drug carrying capacity occupy a remarkable position among the studies conducted in the biomedical field. In this thesis, the synthesis and characterization of a novel hydrogel structure decorated with antimicrobial silver nanoparticles (Ag NPs) were investigated. In this context, poly (vinyl alcohol) (PVA) hydrogels were synthesized by a radiation-initiated crosslinking method, and then the surfaces of the hydrogels were grafted with poly (vinyl pyrrolidone) (PVP) using Atom Transfer Radical Polymerization (ATRP). PVA hydrogels grafted with PVP (PVP@PVA) were modified with Ag NPs via thermal reduction of absorbed Ag+ ions without using any reducing agent (AgNP@PVP@PVA). The mobility of the polymer chains in the PVA hydrogel structure is restricted due to its crosslinked nature. In contrast, grafted PVP chains exhibit higher mobility and, due to their characteristic stabilizing properties, show a high potential to stabilize Ag nanoparticles added later. The PVP layer grafted onto the surface serves as a matrix for the stability of Ag NPs within the hydrogel structure.
The swelling behaviors and pore structures of the synthesized hydrogels were determined by swelling tests and SEM analysis. It was observed that the gels behaved as super absorbent hydrogels by absorbing up to approximately 30 times their initial weight in water. The OH groups of PVA gels were modified with an ATRP initiator, and the amount of brominated OH groups (modification degree) was calculated as approximately 50% using FTIR spectroscopy. Three different methods (calculation of peak areas with FTIR, mass increase, and Thermogravimetric analyzes) were used to determine the degree of modification of PVA gels with PVP. The results obtained from all three methods were close to each other, showing that an approximately 20% PVP modification degree was achieved. The prepared PVP@PVA hydrogel was characterized by SEM analysis after the thermal reduction of silver nanoparticles, and it was found that Ag nanoparticles with an average size of 80 nm were homogeneously distributed along the hydrogel surface. XRD spectroscopy was also used to determine the size distribution of silver nanoparticles. In the XRD pattern, three distinct diffraction peaks corresponding to the (111), (200), and (220) crystal planes of metallic Ag NPs were observed at 2θ = 38.0°, 44.1°, and 65.1°.
The antimicrobial efficacy of hydrogels containing Ag NPs was investigated against cell lines of Proteus mirabilis (Gram-negative bacterium), Staphylococcus epidermidis (Gram-positive bacterium), and Candida tropicalis (yeast). The PVP@PVA hydrogels synthesized within the scope of this thesis were also loaded with oxytetracycline (OTC), a commonly used antimicrobial agent, for a comparative evaluation. Although antibiotics are widely used in many applications, the development of drug resistance in bacteria is a serious issue. Therefore, instead of discovering new antibiotics, it is more appropriate to minimize the dosage of traditional antibiotics. It is crucial to deliver a sufficient bactericidal dose of the antibiotic directly to the infected area at the lowest possible drug dosage without exceeding systemic toxicity levels. One of the main focuses of this thesis is to investigate the simultaneous use of Ag nanoparticles to reduce the bactericidal dose of OTC. In this context, the antimicrobial properties of hydrogels obtained by loading OTC alone (PVP@PVA@OTC) or with Ag NPs (Ag@PVP@PVA@OTC) into the hydrogel structure were also investigated. Our findings showed that both Ag@PVP@PVA and Ag@PVP@PVA@OTC inhibited the growth of all microorganisms tested in this study. However, among the synthesized hydrogels, Ag@PVP@PVA was the only biomaterial that caused both inhibitory and microbicidal effects against all three clinical isolates.
These results are promising, indicating that the Ag NP-loaded hydrogel could be a biomaterial exhibiting higher activity compared to traditional antimicrobial agents in applications requiring high antibacterial functionality. Additionally, the simultaneous use of Ag nanoparticles with an antibiotic may be a strategy to reduce antibiotic dosage to combat bacterial resistance. The antibacterial property added to the PVA hydrogels within the scope of this thesis, which exhibit high oxygen permeability, water absorption capacity, and high biocompatibility, increases the potential of this material for biomedical applications.
