Synthesis and activation of pH-sensitive metal-organic framework Sr(BDC)∞ for oral drug delivery.

Metal-organic frameworks (MOFs) are widely used in the biomedical industry. In this study, we developed a new method for obtaining a metal-organic structure of strontium and terephthalic acid, Sr(BDC), and an alternative activation method for removing DMF from the pores. Sr(BDC) MOFs were successfully prepared and characterized by XRD, FTIR, TGA, and SEM. The importance of the activation steps was confirmed by TGA, which showed that the Sr(BDC)(DMF) sample can contain up to a quarter of the solvent (DMF) before activation. In our study, IR spectroscopy confirmed the possibility of removing DMF by ethanol treatment from the Sr-BDC crystals. A comparative analysis of the effect of the activation method on the specific surface and pore size of Sr-BDC and its sorption properties using the model drug doxorubicin showed that due to the undeveloped surface of the Sr-(BDC)(DMF) sample, it is not possible to obtain an adsorption isotherm and determine the pore size distribution, thus showing the importance of the activation step. Cytotoxicity and apoptosis assays were carried out to study the biological activity of MOFs, and we observed relatively low toxicity in the tested concentration range after 48 h, with over 92% cell survival for Sr(BDC)(DMF) and Sr(BDC)(260 °C), with a decrease only in the highest concentration (800 mg L-1). Similar results were observed in our apoptosis assays, as they revealed low apoptotic population generation of 2.52%, 3.23%, and 2.77% for Sr(BDC)(DMF), Sr(BDC) and Sr(BDC)(260 °C), respectively. Overall, the findings indicate that ethanol-activated Sr(BDC) shows potential as a safe and effective material for drug delivery.

Comparative Analysis of Physical and Chemical Properties of Differently Obtained Zn-Methionine Chelate with Proved Antibiofilm Properties (Part II).

The previously demonstrated activity of aqueous solutions of methionine and zinc salts against biofilms of uropathogenic bacteria prompted us to investigate the structure and properties of zinc methionine complex obtained from such solutions. The paper presents the analysis results of zinc coordination complexes with methionine obtained by synthesis (0.034 mol of L-methionine, 0.034 mol of NaOH, 40 mL of H2O, 0.017 mol ZnSO4, 60 °C) and simple crystallization from water solution (25 mL of a solution containing 134 mmol/L L-methionine, 67 mmol/L ZnSO4, pH = 5.74, I = 0.37 mmol/L, crystallization at room temperature during more than two weeks). IR spectral analysis and X-ray diffraction showed the structural similarity of the substances to each other, in agreement with the data described in the literature. DSC confirmed the formation of a thermally stable (in the range from -30 °C to 180 °C) chelate compound in both cases and indicated the possible retention of the polymorphic two-dimensional structure inherent in L-methionine with the temperature of phase transition 320 K. The crystallized complex had better solubility in water (100 to 1000 mL per 1.0 g) contra the synthesized analog, which was practically insoluble (more than 10 000 mL per 1.0 g). The results of the solubility assessment, supplemented by the results of the dispersion analysis of solutions by the dynamic light scattering method indicated the formation of zinc-containing nanoparticles (80 nm) in a saturated water solution of a crystallized substance, suggesting the crystallized substance may have higher bioavailability. We predicted a possibility of the equivalent existence of optically active cis and trans isomers in methionine-zinc solutions by the close values of formation enthalpy (-655 kJ/mol and -657 kJ/mol for cis and trans forms, respectively) and also illustrated by the polarimetry measurement results (∆α = 0.4°, pH = 5.74, C(Met) = 134 mmol/L; the concentration of metal ion gradually increased from 0 to 134 mmol/L). The obtained results allowed us to conclude that the compound isolated from the solution is a zinc-methionine chelate with the presence of sulfate groups and underline the role of the synthesis route for the biopharmaceutical characteristics of the resulting substance. We provided some quality indicators that it may be possible to include in the pharmacopeia monographs.

Antimicrobial activity of phytofabricated silver nanoparticles using Carica papaya L. against Gram-negative bacteria.

Background and Aim: Antibiotic resistance, especially in Gram-negative bacteria, is a major public health risk affecting all industries requiring the use of antibiotics, including agriculture and animal breeding. This study aimed to use papaya extracts to synthesize silver nanoparticles (AgNPs) and evaluate their antimicrobial activity against various Gram-negative bacteria. Materials and Methods: Silver nanoparticles were synthesized from the aqueous extracts of papaya seed, root, and bark, with AgNO3 used as a reducing agent. The phytofabricated AgNPs were analyzed by ultraviolet-visible absorbance, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy, and photon cross-correlation spectroscopy (PCCS). The disc-diffusion method was used to perform antibacterial analysis, and the minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations were determined. We also investigated the antibiofilm activity of AgNPs and attempted to elucidate the potential mechanism of action on Escherichia coli ATCC 25922. Results: Phytofabrication of AgNPs was successful with papaya root (PR-AgNPs) and papaya seed (PS-AgNPs), but not with papaya bark. Silver nanoparticles using papaya root and PS-AgNPs were both cubic and showed maximum absorbances of 2.6 and 0.3 AUs at 411.6 and 416.8 nm wavelengths and average hydrodynamic diameters X50 of 59.46 ± 7.03 and 66.57 ± 8.89 nm, respectively. The Ag in both AgNPs was confirmed by X-ray fluorescence by a distinctive peak in the spectrum at the silver Kα line of 22.105 keV. Both AgNPs exhibited broad-spectrum antimicrobial and antibiofilm activity against all Gram-negative bacteria, and PR-AgNPs were slightly better than AgNPs-PS. The MIC ranged from 16 µg/mL-128 µg/mL and 16 µg/mL-64 µg/mL, respectively, for PS-AgNPs and PR-AgNPs. The elucidation of the mechanism of action revealed interference with E. coli ATCC 25922 growth kinetics and inhibition of H+-ATPase proton pumps. Conclusion: Papaya seed and root extracts were efficient reducing agents for the biogenic synthesis of AgNPs, with noteworthy antibacterial and antibiofilm activities. Future studies should be conducted to identify the phytochemicals and the mechanism involved in AgNPs synthesis.