Antibiotic resistance of bacteria stimulates the development of new treatment approaches. Piezoelectric-catalysis has attracted much attention due to the possibility to effectively provide antibacterial effect via generation of reactive oxygen species. However, the influence of the surface charge or potential of a piezopolymer on bacteria has not been sufficiently studied so far. This study reports the fabrication and characterization of thin films of piezoelectric polyhydroxybutyrate, polyvinylidene fluoride, and polyvinylidene fluoride trifluoroethylene as well as non-piezoelectric polycaprolactone polymers fabricated using solution casting approach. The piezoelectric coefficient (d33) and surface electric peak-to-peak potential generated by the cyclic mechanical stress applied to the films were measured. Neither any toxic effect of the polymer films nor ultrasound influence on Escherichia coli bacteria behavior is observed. However, significant inhibition of the growth of bacteria is revealed during mechanical stimulation of piezoelectric samples via ultrasound treatment. Thus, this study demonstrates clear bacteriostatic effect of piezoelectric polymers for different tissue engineering applications.
Introduction. Gramicidin S is a peptide antibiotic that has been widely used for more than 70 years. Gramicidin S is available in the form of tablets with a low dosage, which leads to possible deviations in the "Uniformity of dosage" parameter during manufacturing. Another limitation is the presence of lactose and sucrose in the formulation, which limits the drug application by patients demonstrating intolerance. As an alternative, we propose inclusion complexes of gramicidin S with β-cyclodextrin. Aim. The work aims to describe the influence of the methodology to prepare the inclusion complex on the characteristics and properties of the final product. Materials and methods. The gramicidin S -β-cyclodextrin inclusion complex has been prepared by dry mixing, paste complexation, coprecipitation and fluid-bed complexation. The complex formation has been confirmed by 1 H NMR spectroscopy, differential scanning calorimetry and thermogravimetry while the morphology and size by scanning electron microscopy for the solid and dynamic light scattering for the solution. The flowability, slope angle, bulk density of the obtained powders were estimated using the methods described in Russian Pharmacopoeia of the XIV edition. Results and discussion. In the present work, we prepared a set of gramicidin S and β-cyclodextrin inclusion complexes by various approaches. The thermal analysis demonstrated a significant change in the peak referring to phase transition of the substances, indicating the interaction between the components. The 1 H NMR spectroscopy reveals that the L-ornithine amino group is the part of gramicidin S involved in the complexation. Evaluating the technological properties of gramicidin S and β-cyclodextrin inclusion complexes significant variability, which is associated with the particle morphology. Complexes obtained using co-precipitation and fluid-bed complexation methods are more suitable for producing gramicidin S tablet production by direct compression technology. Conclusion. Herein, we demonstrate that the formation of the gramicidin S and β-cyclodextrin inclusion complex occurs through the L-ornithine amino group in the gramicidin S. In addition, depending on the method significant differences in the particle size and shape have been observed. The obtained results could provide valuable information for the development of new gramicidin S buccal formulations, which are more consistent in the "Uniformity of dosage" and allow to avoid the use of lactose and sucrose as excipients.
Introduction. Gramicidin S has been conventionally manufactured as buccal tablets. However, in the past decade, the interest in the development of spray formulations has been growing. Those formulations contain excipients that enhance the solubility of the antibiotic in water solutions. However, the real structure of gramicidin S containing sprays remains unrevealed.Aim. Investigation of colloidal structure and biopharmaceutical properties of new gramicidin S antibacterial composition.Materials and methods. The composition sample was obtained using gramicidin S dihydrochloride, propylene glycol, polysorbate-80, ethanol and purified water. Raman spectroscopy has been performed to determine the composition of the phases. Dynamic light scattering analysis was performed to characterize the composition particles. Release of gramicidin S was performed by dialysis method and the concentration was determined by HPLC. The antimicrobial properties were investigated in accordance with the requirements of the XIV edition of the Russian pharmacopoeia.Results and discussion. Dynamic light scattering analysis results show gramicidin S formulation particles having an average size in solution 5–50 nm and ζ-potential (–1.1: +7.9 mV). Based on the obtained data on the composition properties and formulation parameters it was classified as colloidal solution. The kinetic stability evaluation was performed. We compared the solubility in water and release parameters of the active pharmaceutical ingredient in the native state and in the micelles. The enhancement of the antimicrobial activity of the peptide in the colloidal solution was confirmed and ascribed to the synergic effect gramicidin S – surfactant.Conclusion. We reported the colloidal type of the composition, that aggregate gramicidin S at a concentration of 8 mg/mL. We found that gramicidin S inclusion into the colloidal solution led to significant efficiency increase, which reveals the potential to reduce the drug dose and side effects level.
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