RESUMO
The paper presents the results of the studies performed to establish the effect of the mixtures between limonene and clotrimazole against microbial pathogens involved in dermatological diseases, such as Candida albicans, Staphyloccocus aureus, and Escherichia coli. Preliminary data obtained from the studies performed in microplates revealed a possible synergism between the mixture of clotrimazole and limonene for Staphylococcus aureus. Studies performed "in silico" with programs such as CLC Drug Discovery Workbench and MOLEGRO Virtual Docker, gave favorable scores for docking each compound on a specific binding site for each microorganism. The tests performed for validation, with the clotrimazole (0.1%) and different sources of limonene (1.9% citrus essential oils), showed a synergistic effect on Staphylococcus aureus in the case of the mixtures between clotrimazole and the essential oils of Citrus reticulata or Citrus paradisi. The studies performed on Staphylococcus aureus MRSA showed a synergistic effect between clotrimazole and the essential oils obtained from Citrus bergamia, Citrus aurantium, or Citrus paradisi. In the case of Pseudomonas aeruginosa, essential oils and clotrimazole used alone did not exhibit antimicrobial activities, but the mixtures between clotrimazole and the essential oils of Citrus bergamia or Citrus sinensis exhibited a synergistic antimicrobial effect.
RESUMO
Raw materials, such as collagen and chitosan, obtained from by-products from the food industry (beef hides and crustacean exoskeletons), can be used to obtain collagen-chitosan composite biomaterials, with potential applications in regenerative medicine. Functionalization of these composite biomaterials is a possibility, thus, resulting in a molecule with potential applications in regenerative medicine, namely clotrimazole (a molecule with antibacterial, antifungal, and antitumor activity), at a mass ratio (collagen-chitosan-clotrimazole) of 1:1:0.1. This functionalized composite biomaterial has great potential for application in regenerative medicine, due to the following properties: (1) it is porous, and the pores formed are interconnected, due to the use of a mass ratio between collagen and chitosan of 1:1; (2) the size of the formed pores is between 500-50 µm; (3) between collagen and chitosan, hydrogen bonds are formed, which ensure the unity of composite biomaterial; (4) the functionalized bio-composite exhibits in vitro antimicrobial activity for Candida albicans, Staphylococcus aureus, and Staphylococcus aureus MRSA; for the latter microorganism, the antimicrobial activity is equivalent to that of the antibiotic Minocycline; (5) the proliferation tests performed on a standardized line of normal human cells with simple or composite materials obtained by lyophilization do not show cytotoxicity in the concentration range studied (10-500) µg/mL.
