Interaction studies of cannabidiol with human serum albumin by surface plasmon resonance, spectroscopy, and molecular docking.

The binding interaction of cannabidiol (CBD) and human serum albumin (HSA) under physiological blood pH conditions (pH 7.4) was conducted by surface plasmon resonance (SPR), fluorescence spectroscopy, UV-Visible spectrophotometry, and molecular docking. The responses from SPR measurement increased with the increase in CBD concentration until equilibrium was reached at the equilibrium dissociation constant (KD) of 9.8 × 10-4 M. The results from fluorescence and UV-Visible spectroscopy showed that CBD bound to HSA at one site in a spontaneous manner to form protein-CBD complexes. The quenching process involved both static and dynamic mechanisms while the static mechanism contributed predominantly to the binding between CBD and albumin. The binding constants estimated from the fluorescence studies were from 0.16 × 103 to 8.10 × 103 M-1, which were calculated at different temperature conditions using Stern-Volmer plots. The thermodynamic parameters demonstrated that the binding interaction was a spontaneous reaction as Gibbs free energy had negative values (ΔG = -12.57 to -23.20 kJ.mol-1). Positive ΔH and ΔS values (ΔH = 2.46 × 105 J.mol-1 and ΔS = 869.81 J.mol-1K-1) indicated that the hydrophobic force was the major binding interaction. Finally, confirmation of the type and extent of interaction was provided using UV-spectroscopy and molecular docking studies. The outcomes of this study are expected to serve as a platform to conduct future studies on binding interactions and toxicological research of CBD.Communicated by Ramaswamy H. Sarma.

Formulation Optimization and Stability of Polymyxin B Based on Sodium Deoxycholate Sulfate Micelles.

Polymyxin B (PMB) and sodium deoxycholate sulfate (SDCS) ratios were optimized. The self-assembly of PMB-SDCS was characterized using dynamic light scattering. Five different mole ratios of SDCS to PMB (5:1, 10:1, 15:1, 30:1, and 45:1) were prepared after optimization. FTIR and 1H-NMR were employed to characterize PMB formulations. The chemical stability of PMB was quantified with tandem mass spectrometry. Both PMB and SDCS formed micelles at 14 and 8 µg/ml, respectively. At the critical micelle concentration (CMC), the hydrodynamic diameter of 213 nm was obtained. PMB had a positive charge (+6 mV) while SDCS had a negative charge (‒33 mV). Increasing in SDCS content decreased the charges from ‒6 to ‒25 mV. FTIR revealed H-bonding between PMB and SDCS. The NMR spectra confirmed that chemical shifts of PMB and SDCS did not change. The hydrodynamic size of PMB-SDCS was from 193 to 318 d.nm. Our results suggest that the lower mole ratios of SDCS (< 15:1) were able to stabilize PMB and released PMB within 30 min. Moreover, 5:1 mole ratio maintained the antimicrobial activity against Pseudomonas aeruginosa (MBC = 2 µg/ml). PMB-SDCS micelles of particular mole ratio is able to provide physical and chemical stability of PMB.

Safety and Biocompatibility of Mupirocin Nanoparticle-Loaded Hydrogel on Burn Wound in Rat Model.

Mupirocin nanoparticle-loaded hydrogel (MLH) was successfully developed. This study focused on the safety of cell lines and the biocompatibility of MLH for wound healing in rat models. MLH was assessed by an analysis of cytotoxicity and the secretion of inflammatory cytokines in cell lines. The cytocompatibility of MLH was compared with mupirocin ointment on full-thickness burn wounds in rats. The results indicated that MLH and blank hydrogel had no toxicity to human epidermal keratinocytes and human fibroblast cells. MLH inhibited lipopolysaccharide (LPS) activity in macrophage-like cells resulting in low nitric oxide production and reduced inflammatory cytokine production (interleukin (IL)-1ß) compared with a positive control (LPS only). In burn wounds, MLH and hydrogel healed the wound better than the other groups determined by wound contraction, reduced secretion, and the generation of new blood vessels, as well as promotion of hair follicle cells. Better granulation tissue proliferation, less necrosis, and a lower degree of inflammation were found in the MLH and blank hydrogel than in the mupirocin ointment. The hydrogel group reduced the macrophages (CD68) on day 14 at the edge of the wound. On day 28, T cells (CD3), B cells (CD20), and CD68+ cells were concentrated in the deeper subcutaneous tissue. Additionally, the transforming growth factor ß1 (TGF-ß1) concentration and matrix prometalloproteinase-2/tissue inhibitor of metalloproteinases-2 ratio in the MLH and hydrogel groups were less than those in the other groups. The MLH formulation was safe and effective in burn wound healing. Therefore, MLH formulations are promising candidates for further evaluation in clinical trials.