RESUMEN

Methotrexate (MTX) is a folic acid antagonist routinely used in cancer treatment, characterized by poor water solubility and low skin permeability. These issues could be mitigated by using drug delivery systems, such as functionalized gold nanoparticles (AuNPs), known for their versatility and unique properties. This study aimed to develop multi-shell AuNPs functionalized with MTX for the improvement of MTX antitumoral, antioxidant, and biocompatibility features. Stable phosphine-coated AuNPs were synthesized and functionalized with tailored polyethylene glycol (PEG) and short-branched polyethyleneimine (PEI) moieties, followed by MTX covalent binding. Physicochemical characterization by UV-vis and Fourier-transform infrared spectroscopy (FTIR) spectroscopy, dynamic light scattering (DLS), scanning transmission electron microscopy (STEM), and X-ray photoelectron spectroscopy (XPS) confirmed the synthesis at each step. The antioxidant activity of functionalized AuNPs was determined using DPPH radical scavenging assay, ferric ions' reducing antioxidant power (FRAP), and cupric reducing antioxidant capacity (CUPRAC) assays. Biocompatibility and cytotoxicity were assessed using MTT and LDH assays on HaCaT human keratinocytes and CAL27 squamous cell carcinoma. MTX functionalized AuNPs demonstrated enhanced antioxidant activity and a pronounced cytotoxic effect on the tumoral cells compared to their individual components, highlighting their potential for improving cancer therapy.

Asunto(s)

RESUMEN

Chronic wounds represent one of the complications that might occur from the disruption of wound healing process. Recently, there has been a rise in interest in employing nanotechnology to develop novel strategies for accelerating wound healing. The aim of the present study was to use a green synthesis method to obtain AgNPs/NaLS systems useful for wounds management and perform an in-depth investigation of their behavior during and post-synthesis as well as of their biological properties. The colloids obtained from silver nanoparticles (AgNPs) and commercial sodium lignosulfonate (NaLS) in a single-pot aqueous procedure have been fully characterized by UV-Vis, FT-IR, DLS, TEM, XRD, and XPS to evaluate the synthesis efficiency and to provide new insights in the process of AgNPs formation and NaLS behavior in aqueous solutions. The effects of various concentrations of NaLS (0-16 mg/mL) and AgNO3 (0-20 mM) and of two different temperatures on AgNPs formation have been analyzed. Although the room temperature is feasible for AgNPs synthesis, the short mixing at 70 °C significantly increases the speed of nanoparticle formation and storage stability. In all experimental conditions AgNPs of 20-40 nm in size have been obtained. The antimicrobial activity assessed quantitatively on clinical and reference bacterial strains, both in suspension and biofilm growth state, revealed a broad antimicrobial spectrum, the most intensive inhibitory effect being noticed against Pseudomonas aeruginosa and Escherichia coli strains. The AgNP/NaLS enhanced the NO extracellular release, potentially contributing to the microbicidal and anti-adherence activity by protein oxidation. Both AgNP/NaLS and NaLS were non-hemolytic (hemolytic index<5%, 2.26 ± 0.13% hemolysis) and biocompatible (102.17 ± 3.43 % HaCaT cells viability). The presence of AgNPs increased the antioxidative activity and induced a significant cytotoxicity on non-melanoma skin cancer cells (62.86 ± 8.27% Cal-27 cells viability). Taken together, all these features suggest the multivalent potential of these colloids for the development of novel strategies for wound management, acting by preventing infection-associated complications and supporting the tissue regeneration.

RESUMEN

Aim: A series of new hybrid molecules with two iodine atoms on the sides were synthesized. Methods: A one-pot, two-component method with trifluoroacetic acid as an effective catalyst to obtain dihydro-pyrrol-2-one compounds was developed. Short reaction times, a cheap catalyst, high yields and clean work-up are benefits of this method. Results: The chemical structures of the newly synthesized compounds were verified through spectroscopic techniques. Their antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans was tested in vitro. Conclusion: NC- and OH- radicals confer broad-spectrum antimicrobial activity, including against Gram-positive and Gram-negative bacteria and yeasts. Compounds 3g >7 and >9 were most active on the two bacterial species, while 3l >9 and >3i were most active against the fungal strain.

RESUMEN

The essential oil extracted by hydrodistillation from Romanian Artemisia annua aerial parts was characterized by GC/MS analysis, which allowed the identification of 94.64% of the total oil composition. The main components were camphor (17.74%), α-pinene (9.66%), germacrene D (7.55%), 1,8-cineole (7.24%), trans-ß-caryophyllene (7.02%), and artemisia ketone (6.26%). The antimicrobial activity of this essential oil was evaluated by determining the following parameters: minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), minimal fungicidal concentration (MFC), and minimal biofilm eradication concentration (MBEC). Moreover, the soluble virulence factors were quantified with different biochemical substrates incorporated in the culture media. The reference and resistant, clinical strains proved to be susceptible to the A. annua oil, with MICs ranging from 0.51 to 16.33 mg/ml. The tested essential oil also showed good antibiofilm activity, inhibiting both the initial stage of the microbial cell adhesion to the inert substratum and the preformed mature biofilm. When used at subinhibitory concentrations, the essential oil proved to inhibit the phenotypic expression of five soluble virulence factors (hemolysins, gelatinase, DNase, lipases, and lecithinases). Briefly, the present results showed that the A. annua essential oil contained antimicrobial compounds with selective activity on Gram-positive and Gram-negative bacterial strains as well as on yeast strains and which also interfere with the expression of cell-associated and soluble virulence factors.

Asunto(s)