Design, Characterization, and Anticancer and Antimicrobial Activities of Mucoadhesive Oral Patches Loaded with Usnea barbata (L.) F. H. Wigg Ethanol Extract F-UBE-HPMC
2022
Violeta Popovici | Elena Matei | Georgeta Camelia Cozaru | Laura Bucur | Cerasela Elena Gîrd | Verginica Schröder | Emma Adriana Ozon | Mirela Adriana Mitu | Adina Magdalena Musuc | Simona Petrescu | Irina Atkinson | Adriana Rusu | Raul-Augustin Mitran | Mihai Anastasescu | Aureliana Caraiane | Dumitru Lupuliasa | Mariana Aschie | Eugen Dumitru | Victoria Badea
The oral cavity&rsquo:s common pathologies are tooth decay, periodontal disease, and oral cancer: oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy, with a high mortality rate. Our study aims to formulate, develop, characterize, and pharmacologically investigate the oral mucoadhesive patches (F-UBE-HPMC) loaded with Usnea barbata (L.) F.H. Wigg dry ethanol extract (UBE), using HPMC K100 as a film-forming polymer. Each patch contains 312 µ:g UBE, with a total phenolic content (TPC) of 178.849 µ:g and 33.924 µ:g usnic acid. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were performed for their morphological characterization, followed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Pharmacotechnical evaluation involved the measurement of the specific parameters for mucoadhesive oral patches as follows: weight uniformity, thickness, folding endurance, tensile strength, elongation, moisture content, pH, disintegration time, swelling rate, and ex vivo mucoadhesion time. Thus, each F-UBE-HPMC has 104 ±: 4.31 mg, a pH = 7.05 ±: 0.04, a disintegration time of 130 ±: 4.14 s, a swelling ratio of 272 ±: 6.31% after 6 h, and a mucoadhesion time of 102 ±: 3.22 min. Then, F-UBE-HPMCs pharmacological effects were investigated using brine shrimp lethality assay (BSL assay) as a cytotoxicity prescreening test, followed by complex flow cytometry analyses on blood cell cultures and oral epithelial squamous cell carcinoma CLS-354 cell line. The results revealed significant anticancer effects by considerably increasing oxidative stress and blocking DNA synthesis in CLS-354 cancer cells. The antimicrobial potential against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27353, Candida albicans ATCC 10231, and Candida parapsilosis ATCC 22019 was assessed by a Resazurin-based 96-well plate microdilution method. The patches moderately inhibited both bacteria strains growing and displayed a significant antifungal effect, higher on C. albicans than on C. parapsilosis. All these properties lead to considering F-UBE-HPMC suitable for oral disease prevention and therapy.
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