Encapsulation of Zataria multiflora essential oil in polyvinyl alcohol/chitosan/gelatin thermo-responsive hydrogel: Synthesis, physico-chemical properties, and biological investigations.

Zataria multiflora essential oil is a natural volatile plant product whose therapeutic applications require a delivery platform. Biomaterial-based hydrogels have been extensively used in biomedical applications, and they are promising platforms to encapsulate essential oils. Among different hydrogels, intelligent hydrogels have recently attracted many interests because of their response to environmental stimuli such as temperature. Herein, Zataria multiflora essential oil is encapsulated in a polyvinyl alcohol/chitosan/gelatin hydrogel as a positive thermo-responsive and antifungal platform. According to the optical microscopic image, the encapsulated spherical essential oil droplets reveal a mean size of 1.10 ± 0.64 μm, which are in consistent with the SEM imaging results. Encapsulation efficacy and loading capacity are 98.66 % and 12.98 %, respectively. These results confirm the successful efficient encapsulation of the Zataria multiflora essential oil within the hydrogel. The chemical compositions of the Zataria multiflora essential oil and the fabricated hydrogel are analyzed by gas chromatography-mass spectroscopy (GC-MS) and Fourier transform infrared (FTIR) techniques. It is found that thymol (44.30 %) and γ-terpinene (22.62 %) are the main constituents of the Zataria multiflora essential oil. The produced hydrogel inhibits the metabolic activity of Candida albicans biofilms (∼60-80 %), which can be related to the antifungal activity of the essential oil constituents and chitosan. Based on the rheological results, the produced thermo-responsive hydrogel shows a gel-sol viscoelastic transition at a temperature of 24.5 °C. This transition leads to a facile release of the loaded essential oil. The release test depicts that about 30 % of Zataria multiflora essential oil is released during the first 16 min. In addition, 2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay demonstrates that the designed thermo-sensitive formulation is biocompatible with high cell viability (over 96 %). The fabricated hydrogel can be deemed as a potential intelligent drug delivery platform for controlling cutaneous candidiasis due to antifungal effectiveness and less toxicity, which can be a promising alternative to traditional drug delivery systems.