RESUMEN
The global threat of infectious diseases and antibiotic resistance calls for the development of potent antimicrobial agents integrated with hydrogel for effective control and treatment. Hydrogel is advanced biomaterials compounds. Hydrogel is an advanced biomaterial compound that offers tunable physical and chemical properties, which can be tailored to specific biomedical applications. This study investigates the antibacterial properties of pectin/polyethylene oxide (PEC/PEO)-based poly acrylamide hydrogels containing 5 wt% nano-metal oxides (TiO2, CaO, MgO, and ZnO) synthesized through gamma irradiation at a dose of 30 kGy. This technique allows for sterilization and effectively incorporating the metal oxide nanoparticles within the hydrogel matrix. Characterization of the nanocomposites is performed using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Incorporating metal oxide nanoparticles induces noticeable changes in the FTIR spectra, confirming interactions between the nanoparticles and the hydrogel matrix. The antibacterial activity of the nanocomposites is evaluated against different bacteria, and the results demonstrate significant inhibitory effects, especially for MgO- and ZnO-hydrogel nanocomposites against P. mirabilis, S. aureus, P. aeruginosa, and C. albicans, highlighting their potential as antimicrobial agents. The 5 wt% of MgO, ZnO, TiO2 and CaO inside PEO/PEC-co-AAm hydrogel nanocomposites exhibited significant inhibitory effects, with a respective optical density at λ = 600 nm (OD600) values of 0.896 nm, 0.986 nm, 1.250 nm, and 1.980 nm compared to the control and hydrogel alone (OD600 values of 2.88 nm and 2.72 nm, respectively). The antibacterial activity of the (MgO-, ZnO-, TiO2-, and CaO-hydrogel) was enhanced, resulting in the inhibition of S. aureus growth by approximately 68.89 %, 65.86 %, 56.25 %, and 31.94 %, respectively. Incorporating nanoparticles into a hydrogel matrix introduces novelty by preventing their aggregation and synergistically enhancing the antibacterial activity. The hydrogel's porous structure and water content facilitate the physical entrapment of bacteria and promote proximity to the metal oxide nanoparticles, resulting in improved interaction and antimicrobial effectiveness. Moreover, the hydrogel ability to absorb and entrap resistance compounds released by bacteria, coupled with its ability to supply water for the generation of reactive oxygen species, further contributes to its antimicrobial properties.
Asunto(s)
Nanopartículas del Metal , Nanocompuestos , Óxido de Zinc , Hidrogeles/farmacología , Hidrogeles/química , Óxido de Zinc/farmacología , Óxido de Zinc/química , Óxido de Magnesio/farmacología , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Óxidos/farmacología , Materiales Biocompatibles/farmacología , Nanopartículas del Metal/química , Bacterias , Agua/farmacología , Difracción de Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Nanocompuestos/químicaRESUMEN
PURPOSE: Inhalable pulmonary delivery of isoniazid (INH) may improve the efficacy and reduce drug resistance. METHOD: INH-loaded chitosan microparticles (Cs-Mps-1-3) were prepared as an inhalable carrier for the previously prepared INH-loaded polyvinylpyrrolidone/polyitaconic acid nanoparticles (NPs) using spray-drying technique. Here, Cs-Mps-1-3 are composed of Cs: INH-loaded NPs: Free INH at w/w ratios (1:1:0), (1: 0:1), and (1:1:1), respectively. Subsequently, the prepared Cs-Mps-1-3 characterizations were studied. RESULTS: Cs-Mps-1-3 showed a spherical, smooth, positively charged surface (ζ-potential values +20.2, +28.7, and +22.6) and a size range 1.52-3.12 µm. In addition, Carr's compressibility indices of Cs-Mps-1-3 were 32.5%, 24.8%, and 28.02%, respectively. The in vitro INH released showed good correlation with first-order pattern, with predominance of the diffusion-controlled mechanism. In vitro aerodynamic deposition of Cs-MPs-3 possessed 56.81% effective fine particle fraction with lower impaction loss and device retention (10.47% and 30.9% at mouth and throat and at stage 1, respectively). The minimum inhibitory concentration of Cs-Mps-3 displayed 63-fold more inhibition effects on Mycobacterium tuberculosis than INH solution, owing to the combined effect of positively charged Cs-Mps with their facilitating bacterial cell surface binding and cellular penetration activity of NPs. CONCLUSION: The promising potential of Cs-Mps-3 as an inhalable carrier for pulmonary delivery of INH is recommended.
Asunto(s)
Antituberculosos/administración & dosificación , Quitosano/química , Isoniazida/administración & dosificación , Pulmón/metabolismo , Mycobacterium tuberculosis/efectos de los fármacos , Administración por Inhalación , Antituberculosos/farmacocinética , Antituberculosos/farmacología , Portadores de Fármacos/química , Liberación de Fármacos , Isoniazida/farmacocinética , Isoniazida/farmacología , Pruebas de Sensibilidad Microbiana , Nanogeles , Tamaño de la Partícula , Povidona/química , Succinatos/química , Distribución TisularRESUMEN
PURPOSE: Preparation of Isoniazid (INH) loaded nanogel particles using gamma radiation as safe, simple, cheap and reproducible technique for promoting mycobacterial killing in a lower-dose system aiming in developing of drug resistance. METHODS: Polymeric pH-sensitive nanogels were prepared by gamma radiation-induced polymerization of Acrylic acid (AAc) or Itaconic acid (IA), in aqueous solution of polyvinylpyrrolidone (PVP), as template polymer. The prepared nanogels were utilized for encapsulation of INH. 31X22 factorial design was employed for optimization and exploring the effect of radiation dose (X1) (30-50kGy), ratio of PVP: acid (X2) (50:50-30:70) and type of acid (X3) on the prepared nanogel characterization RESULTS: The optimized levels of X1, X2 and X3 were (50 KGy, 30:70 and Itaconic acid, respectively), with a desirability of 0.959. In-vitro INH release rate from the prepared nanogels decreased with increasing gamma radiation doses, with the predominance of the diffusion mechanism for drug release pattern. In addition, it was perceived that the minimum inhibitory concentration (MIC) of INH loaded PVP/PIA nanogels on Mycobacteria Tuberculosis was 8 folds lower than that of INH solution. CONCLUSION: The prospective of PVP-K90/PIA was recommended as a smart candidate for delivery of INH with promising achievements against tuberculosis than free drug. Graphical abstract Mechanism of formation and loading of Isoniazid PVP/PIA nanogel.