Formulation and Characterization of New Polymeric Systems Based on Chitosan and Xanthine Derivatives with Thiazolidin-4-One Scaffold

Abstract

In the past many research studies have focused on the thiazolidine-4-one scaffold, due to the important biological effects associated with its heterocycle. This scaffold is present in the structure of many synthetic compounds, which showed significant biological effects such as antimicrobial, antifungal, antioxidant, anti-inflammatory, analgesic, antidiabetic effects. It was also identified in natural compounds, such as actithiazic acid, isolated from Streptomyces strains. Starting from this scaffold new xanthine derivatives have been synthetized and evaluated for their antibacterial and antifungal effects. The antibacterial action was investigated against Gram positive (Staphyloccoccus aureus ATCC 25923, Sarcina lutea ATCC 9341) and Gram negative (Escherichia coli ATCC 25922) bacterial strains. The antifungal potential was investigated against Candida spp. (Candida albicans ATCC 10231, Candida glabrata ATCC MYA 2950, Candida parapsilosis ATCC 22019). In order to improve the antimicrobial activity, the most active xanthine derivatives with thiazolidine-4-one scaffold (XTDs: 6c, 6e, 6f, 6k) were included in a chitosan based polymeric matrix (CS). The developed polymeric systems (CS-XTDs) were characterized in terms of morphological (aspect, particle size), physic-chemical properties (swelling degree), antibacterial and antifungal activities, toxicity, and biological functions (bioactive compounds loading, entrapment efficiency). The presence of xanthine-thiazolidine-4-one derivatives into the chitosan matrix was confirmed using Fourier transform infrared (FT-IR) analysis. The size of developed polymeric systems, CS-XTDs, ranged between 614 µm and 855 µm, in a dry state. The XTDs were encapsulated into the chitosan matrix with very good loading efficiency, the highest entrapment efficiency being recorded for CS-6k, which ranged between 87.86 ± 1.25% and 93.91 ± 1.41%, depending of the concentration of 6k. The CS-XTDs systems showed an improved antimicrobial effect with respect to the corresponding XTDs. Good results were obtained for CS-6f, for which the effects on Staphylococcus aureus ATCC 25923 (21.2 ± 0.43 mm) and Sarcina lutea ATCC 9341 (25.1 ± 0.28 mm) were comparable with those of ciprofloxacin (25.1 ± 0.08 mm/25.0 ± 0.1 mm), which were used as the control. The CS-6f showed a notable antifungal effect, especially on Candida parapsilosis ATCC 22019 (18.4 ± 0.42 mm), the effect being comparable to those of nystatin (20.1 ± 0.09 mm), used as the control. Based on the obtained results these polymeric systems, consisting of thiazolidine-4-one derivatives loaded with chitosan microparticles, could have important applications in the food field as multifunctional (antimicrobial, antifungal, antioxidant) packaging materials.