Design, synthesis, spectroscopic characterization, in-vitro antibacterial evaluation and in-silico analysis of polycaprolactone containing chitosan-quercetin microspheres.

Aim of present study was to synthesize a novel chitosan-quercetin (CTS-QT) complex by making a carbodiimide linkage using maleic anhydride as cross-linker and to investigate its enhanced antibacterial and antioxidant activities as compare to pure CTS and QT. Equimolar concentration of QT and maleic anhydride were used to react with 100 mg CTS to form CTS-QT complex. For this purpose, three bacterial strains namely E. Coli, S. Aureus and P. Aeruginosa were used for in-vitro antibacterial analysis (ZOI, MIC, MBC, checker board and time kill assay). Later molecular docking studies were performed on protein structure of E. Coli to assess binding affinity of pure QT and CTS-QT complex. MD simulations with accelerated settings were used to explore the protein-ligand complex's binding interactions and stability. Antioxidant profile was determined by performing DPPH• radical scavenging assay, total antioxidant capacity (TAC) and total reducing power (TRP) assays. Delivery mechanism to CTS-QT complex was improved by synthesizing polycaprolactone containing microspheres (CTS-QT-PCL-Levo-Ms) using Levofloxacin as model drug to enhance their antibacterial profile. Resulted microspheres were evaluated by particle size, charge, surface morphology, in-vitro drug release and hemolytic profile and are all were found within limits. Antibacterial assay revealed that CTS-QT-PCL-Levo-Ms showed more than two folds increased bactericidal activity against E. Coli and P. Aeruginosa, while 1.5 folds against S. Aureus. Green colored formation of phosphate molybdate complexes with highest 85 ± 1.32% TAC confirmed its antioxidant properties. Furthermore, molecular docking and dynamics studies revealed that CTS-QT was embedded nicely within the active pocket of UPPS with binding energy greater than QT with RSMD value of below 1.5. Conclusively, use of maleic acid, in-vitro and in-silico antimicrobial studies confirm the emergence of CTS-QT complex containing microspheres as novel treatment strategy for all types of bacterial infections.Communicated by Ramaswamy H. Sarma.

Wound-Healing and Antibacterial Activity of the Quercetin-4-Formyl Phenyl Boronic Acid Complex against Bacterial Pathogens of Diabetic Foot Ulcer.

Complications of diabetic foot can be prevented using a naturally occurring, efficient, and newly synthesized antimicrobial agent. The purpose of the study was to improve wound healing and antibacterial effects of quercetin and its esterified complex with 4-formyl phenyl boronic acid (4FPBA-Q) compared with phenytoin. The formation of the 4FPBA-Q complex was confirmed by thin-layer chromatography (TLC), Fourier transform infrared (FTIR) spectroscopy, and mass spectrometry (MS). The prepared 4FPBA-Q complex was used against Gram-positive bacteria along with Gram-negative bacteria, and more than 2-fold decrease in minimum inhibitory concentrations (MIC) was observed compared to pure quercetin. Scanning electron microscopic images of Pseudomonas aeruginosa and Staphylococcus aureus showed their complete destruction after incubation with the 4FPBA-Q complex even after 3 h. Interestingly, wound-healing properties of the 4FPBA-Q complex in infected diabetic rats increased from 64 to 99% as compared to phenytoin, which were increased from those of noninfected diabetic rats. Furthermore, histopathological evaluations showed significantly enhanced wound healing, re-epithelialization, fibroblasts, and angiogenesis in wounds of diabetic rats after 10 days. Conclusively, reduction in the primary irritation index (PDII) and improved antibacterial and wound-healing properties render the 4FPBA-Q complex ideal for diabetic foot ulcer treatment.