Resistance to currently available antifungal agents raises the need to develop alternative remedies. Candida albicans is the most common opportunistic pathogenic fungus of humans, colonizing in the genital and intestinal mucosa, skin, and oral-nasal cavity and reducing quality of life. Herein, essential oil from grapefruit (Citrus paradise) peels was obtained by hydrodistillation, and the remaining plant material was sequentially subjected to supercritical carbon dioxide (SC-CO2) extraction to determine the conditions for maximizing phenolic compounds. A statistical design was used to evaluate the effect of temperature (30, 50, 70 °C), pressure (80, 150, 220 bar), and ethanol as a cosolvent (0%, 10%, and 20% v/v). Essential oil and SC-CO2 extracts were mixed at various ratios to develop an effective antifungal formulation. Subsequently, fungal infection was modeled by coculturing C. albicans with human skin keratinocytes (HaCaT) to mimic dermal mycoses, endothelial cells (HUVEC) to evaluate vascular fate, and cervical adenocarcinoma (HeLa) cells to represent additional genital mycoses. Treatment with essential oil and extract (25:75%) formulation for 8 h exhibited slight cytotoxicity toward HeLa cells, no toxicity toward HaCaT and HUVECs, whereas inhibition of C. albicans. Considering the clinical significance, such in vitro models are essential to screen potential compounds for the treatment of opportunistic fungal infections.
The temporomandibular joint (TMJ) is commonly affected during fundamental oral activities, reducing the quality of life. Herein, we synthesized a heparinconjugated poloxamer hydrogel (HEP) as a thermo-responsive injectable hydrogel for the treatment of TMJ disorders. While the gelation temperature of synthesized HEP (25% [w/v]) was 29.8-30.0 C, there was a slight difference between loss and storage modulus. HEP decreased the friction of the TMJ, thus requires less energy during load-bearing jaw movement in comparison to POL. Moreover, the oscillation test dependent on strain ranges from 0.01% to 1000% validated that POL and HEP3 hydrogels showed a similar critical strain of about 5.6%. The total elastic recovery percentage of HEP3 (53.50%) was higher than POL (45.55%), indicating a better recovery of the deformed hydrogel structure. Along with the suitable viscoelastic properties for temporomandibular cavity, both hydrogels increased the proliferation of fibroblasts (L929) and chondrocytes (ATDC5) (cell viabilities were above 100%). However, newly synthesized HEP induced differentiated cell proliferation of chondrogenic cells at increasing concentrations up to 0.0156 mg/mL (p < 0.0001) compared to POL and the control group. The promising rheological properties and effects on chondrogenic cell proliferation of injectable heparin-conjugated hydrogel make them candidates for intra-articular injections used for the treatment of TMJ.
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