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[This corrects the article DOI: 10.1021/acsomega.3c00914.].
RESUMO
A middle ear infection occurs due to the presence of several microorganisms behind the eardrum (tympanic membrane) and is very challenging to treat due to its unique location and requires a well-designed treatment. If not treated properly, the infection can result in severe symptoms and unavoidable side effects. In this study, excellent biocompatible ethyl cellulose (EC) and biodegradable polyhydroxybutyrate (PHB) biopolymer were used to fabricate drug-loaded nanofiber scaffolds using an electrospinning technique to overcome antibiotic overdose and insufficient efficacy of drug release during treatment. PHB polymer was produced from Halomonas sp., and the purity of PHB was found to around be 90 %. Additionally, ciprofloxacin (CIP) and amoxicillin (AMX) are highly preferable since both drugs are highly effective against gram-negative and gram-positive bacteria to treat several infections. Obtained smooth nanofibers were between 116.24 and 171.82 nm in diameter and the addition of PHB polymer and antibiotics improved the morphology of the nanofiber scaffolds. Thermal properties of the nanofiber scaffolds were tested and the highest Tg temperature resulted at 229 °C. The mechanical properties of the scaffolds were tested, and the highest tensile strength resulted in 4.65 ± 6.33 MPa. Also, drug-loaded scaffolds were treated against the most common microorganisms that cause the infection, such as S.aureus, E.coli, and P.aeruginosa, and resulted in inhibition zones between 10 and 21 mm. MTT assay was performed by culturing human adipose-derived mesenchymal stem cells (hAD MSCs) on the scaffolds. The morphology of the hAD MSCs' attachment was tested with SEM analysis and hAD MSCs were able to attach, spread, and live on each scaffold even on the day of 7. The cumulative drug release kinetics of CIP and AMX from drug-loaded scaffolds were analysed in phosphate-buffered saline (pH: 7.4) within different time intervals of up to 14 days using a UV spectrophotometer. Furthermore, the drug release showed that the First-Order and Korsmeyer-Peppas models were the most suitable kinetic models. Animal testing was performed on SD rats, matrix and collagen deposition occurred on days 5 and 10, which were observed using Hematoxylin-eosin and Masson's trichrome staining. At the highest drug concentration, a better repair effect was observed. Results were promising and showed potential for novel treatment.
Assuntos
Amoxicilina , Antibacterianos , Celulose , Ciprofloxacina , Nanofibras , Celulose/química , Celulose/análogos & derivados , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Nanofibras/química , Animais , Ratos , Amoxicilina/farmacologia , Amoxicilina/química , Antibacterianos/farmacologia , Antibacterianos/química , Hidroxibutiratos/química , Hidroxibutiratos/farmacologia , Humanos , Otite Média/tratamento farmacológico , Otite Média/microbiologia , Poliésteres/química , Liberação Controlada de Fármacos , Alicerces Teciduais/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Proibitinas , Portadores de Fármacos/química , MasculinoRESUMO
In this study, two-layer poly(vinyl alcohol)/gelatin (PVA/GEL) nanofiber patches containing cinnamaldehyde (CA) in the first layer and gentamicin (GEN) in the second layer were produced by the electrospinning method. The morphology, chemical structures, and thermal temperatures of the produced pure (PVA/GEL), CA-loaded (PVA/GEL/CA), GEN-loaded (PVA/GEL/GEN), and combined drug-loaded (PVA/GEL/CA/GEN) nanofiber patches were determined by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and differential scanning calorimetry, respectively. Their mechanical properties, swelling and degradation behavior, and drug release kinetics were investigated. SEM images showed that both drug-free and drug-loaded nanofiber patches possess smooth and monodisperse structures, and nanofiber size increase occurred as the amount of drug increased. The tensile test results showed that the mechanical strength decreased as the drug was loaded. According to the drug release results, CA release ended at the 96th hour, while GEN release continued until the 264th hour. The antibacterial and antibiofilm activities of PVA/GEL, PVA/GEL/CA, PVA/GEL/GEN, and PVA/GEL/CA/GEN nanofiber patches against Pseudomonas aeruginosa and Staphylococcus aureus were evaluated. Results showed that PVA/GEL/GEN and PVA/GEL/CA/GEN nanofiber patches have excellent antibacterial and antibiofilm activities. Moreover, all materials were biocompatible, with no cytotoxic effects in the mammalian cell model for 8 days. PVA/GEL/GEN nanofiber patches were the most promising material for a high cell survival ratio, which was confirmed by SEM images. This research aims to develop an alternative method to stop and treat the rapid progression of bacterial keratitis.