Oxytetracycline-Copper (II) Complex Loaded on PVA/AgO Hydrogel for Controlled Release Kinetics: Engineering, Enhanced Biological Potential and Molecular Docking
摘要
The metallic complexes with the pharmaceutical drugs have improved the mechanical strength, site action, enhanced stability and biological activities. In this research work, the controlled release from PVA/AgO nanobiocomposite hydrogel and biological potential of oxytetracycline (OTC) and Cu-OTC complex were compared. The OTC which is an antimicrobial class of tetracycline was altered chemically with the coordination complex of the copper ion. The OTC complex with copper (II) using copper chloride and OTC in one-pot synthesis was obtained to explore the biological activities and release kinetics. The OTC methanolic solution was mixed in copper chloride methanolic solution and then it was refluxed for three hours to get the fine crystals of Cu-OTC complex. The prepared complex was characterized using various techniques as measurement of melting points, UV-Vis spectrophotometer, FTIR spectroscopy, Surface-Enhanced Raman spectroscopy (SERS) along Principal Component analysis (PCA), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), NMR (1H & 13C), SEM, EDX and X-ray Diffraction (XRD). The prepared complex and OTC were loaded on PVA/AgO hydrogel and controlled release in phosphate buffer solution of pH 7.4 at 37 °C for 33 h with the interval gap of 3 h was evaluated by using UV-Vis spectrophotometer. The Higuchi and Korsmeyer-Peppas models were employed to study the release kinetics. The antibacterial activity, MIC, and MBC against E. coli and S. aureus bacteria, hemolytic analysis and cytotoxicity against human colon cancer cells (SW480) were also performed to analyze the biological potential of the prepared complex. The molecular docking was also performed to compare the antibacterial and cytotoxicity of OTC and Cu-OTC complex. The stoichiometry determined by Job’s method proved the 1:1 Cu-OTC complex which is consistent with spectroscopic results. The Cu-OTC complex was found to have better antibacterial properties than free OTC based on increased yielding of broader zones of inhibition and reduced MIC/MBC. Diffusion controlled kinetics Studies of controlled release showed sustained release behavior at the PVA/AgO hydrogel. The cytotoxicity analysis showed that the Cu-OTC complex inhibited the growth of SW480 cells more than OTC did without causing significant hemocompatibility loss.