Abstract
A series of hydrogels with a specific release profile of linezolid was successfully synthesized. The hydrogels were synthesized by cross-linking polyvinyl alcohol (PVA) and aliphatic dicarboxylic acids, which include succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The three crosslinked hydrogels were prepared by esterification and characterized by equilibrium swelling ratio, infrared spectroscopy, thermogravimetric analysis, mechanical properties, and scanning electron microscopy. The release kinetics studies of the linezolid from prepared hydrogels were investigated by cumulative drug release and quantified by chromatographic techniques. Mathematical models were carried out to understand the behavior of the linezolid release. These data revealed that the sustained release of linezolid depends on the aliphatic dicarboxylic acid chain length, their polarity, as well as the hydrogel crosslinking degree and mechanical properties. The in vitro antibacterial assay of hydrogel formulations was assessed in an Enterococcus faecium bacterial strain, showing a significant activity over time. The antibacterial results were consistent with cumulative release assays. Thus, these results demonstrated that the aliphatic dicarboxylic acids used as crosslinkers in the PVA hydrogels were a determining factor in the antibiotic release profile.
Highlights
Multidrug-resistant (MDR) bacteria or “superbugs” represent one of the most important challenges to public health and pose a huge economic burden on global health care [1,2]
Polyvinyl alcohol (PVA) 30–60 KDa, succinic acid (SA), glutaric acid (GA) adipic acid (AA), NaHCO3, acetonitrile (HPLC grade), and linezolid analytical standards were purchased from Sigma-Aldrich
The methodology for preparing the hydrogels was performed through the esterification of PVA with aliphatic dicarboxylic acids (ADAs) according to the method from Rodríguez Nuñez et al with minor modifications [16]
Summary
Multidrug-resistant (MDR) bacteria or “superbugs” represent one of the most important challenges to public health and pose a huge economic burden on global health care [1,2]. The World Health Organization (WHO) has classified Enterococcus faecium as one of the primary drug-resistant pathogens posing the most significant risk to public health This bacterium causes urinary tract infections, hospital-acquired bloodstream infections, abdominal and pelvic abscesses, endocarditis, and chronic periodontitis. Recent studies indicate that the effectiveness of antibacterial agents is better when they are released through drug delivery systems. These systems could slow down the progression of bacterial resistance to antibiotics [7,8]. The purpose of this study was to develop hydrogels with ADAs of variable chain lengths as crosslinker agents featuring the tunable sustained release of linezolid
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