In vitro and in vivo effects of the combination of myricetin and miconazole nitrate incorporated to thermosensitive hydrogels,on C. albicans biofilms |
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| Institution: | 1. School of Pharmacy, Health Science Center, Xi''an Jiaotong University, Xi''an, 710061, P. R. China;2. Biobank, The first affiliated hospital of Xi''an Jiaotong University, Xi''an, 710054, P. R. China;1. Research Institute of Atherosclerotic Disease, Xi''an Jiaotong University Cardiovascular Research Center, Xi''an, Shaanxi 710061, China;2. Laboratory Animal Center, Health Science Center, Xi''an Jiaotong University, Xi''an, Shaanxi 710061, China;3. Department of Pharmacy, Eighth Hospital of Xi''an City, Xi''an, Shaanxi 710061, China;4. Department of Pharmacology, Health Science Center, Xi''an Jiaotong University, Xi''an, Shaanxi 710061, China;5. School of Pharmacy, Health Science Center, Xi''an Jiaotong University, Xi''an, Shaanxi 710061, China;1. Institute of Pharmacy, Bundelkhand University, Jhansi, India 284128;2. Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Banaras Hindu University, (IIT-BHU), Varanasi, India 221005;3. Pharmaceutical Science Laboratory, Faculty of Science and Engineering, Abo Akademi University, Turku, Finland 20520;4. School of Medical and Allied Sciences, G.D. Goenka University, Gurgaon Sohna Road, Gurgaon, India 122103;5. Pharmaceutical Chemistry Department, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;6. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India;1. Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Campus Reitor João David Ferreira Lima, s/n - Trindade, Florianópolis - SC, 88040-900, Brazil;2. Department of Chemistry, Federal University of Santa Catarina, Campus Reitor João David Ferreira Lima, s/n - Trindade, Florianópolis - SC, 88040-900, Brazil;3. Department of Civil Engineering, Federal University of Santa Catarina, Campus Reitor João David Ferreira Lima, s/n - Trindade, Florianópolis - SC, 88040-900, Brazil |
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| Abstract: | BackgroundCandida albicans-related infections are common infections in clinic, among which biofilm-associated infections are most devastating and challenging to overcome. Myricetin (MY) is a plant-derived natural product with various pharmacological activities. Its anti-biofilm effect against C. albicans and its ability to increase the antifungal effect of miconazole nitrate (MN) were unclear and yet need to be explored.Hypothesis/PurposeIn this study the anti-biofilm effect of MY and its ability to increase the antifungal effect of MN were investigated in vitro and in vivo.Study design and methodsMY or/and MN were incorporated into a thermosensitive hydrogel (TSH) of poloxamer. The safety of MY or/and MN loaded TSHs towards human umbilical vein endothelial cells (HUVEC) was evaluated by a MTT assay and the in vivo safety towards mice knees was confirmed by histopathological examination. The anti-biofilm effect of MY and its ability to increase the antifungal effect of MN were investigated in vitro with C. albicans ATCC 10231 by broth microdilution method, crystal violet staining and scanning electron microscopy (SEM), as well as in vivo in an established mouse model of periprosthetic joint infection (PJI) by SEM, histological analysis, microorganism culture and detection of the serum levels of interleukin-6 (IL-6). The mechanism of action of MY was analyzed by qRT-PCR assay with C. albicans SC5314.ResultsOur results showed that MY and MN incorporated into TSHs exhibited good stability and safety, excellent temperature sensitivity and controlled drug release property. MY (5-640 µg/ml) exhibited no effect on C. albicans cell viability and MY (≥80 µg/ml) showed a significantly inhibitory effect on biofilm formation. MIC50 (the lowest concentrations of drugs resulting in 50% decrease of C. albicans growth) and MIC80 (the lowest concentrations of drugs resulting in 80% decrease of C. albicans growth) of MN were respectively decreased from 2 µg/ml to 0.5 µg/ml and from 4 µg/ml to 2 µg/ml when used in combination with MY (80 µg/ml). The mouse PJI was effectively prevented by MY and MN incorporated into TSH.ConclusionsLocal application of MY and MN incorporated into TSH might be useful for clinical biofilm-associated infections. |
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