Scientific Reports
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2021
·Vol. 11
·期 1
·1-8
·
IF 4.38
Xu Xue,Naseri Ali,Houbraken Jos,Akbari Farzaneh,Wang Xiaodong,Zhao Rongfen,Zhang Hong,Najafzadeh Mohammad Javad,Deng Shuwen
Aspergillus species are emerging causative agents of non-dermatophyte mold onychomycosis. In this study, 48 Aspergillus isolates were obtained from patients with onychomycosis in Mashhad, Iran, during 2015–2018. The aim is to identify the Aspergillus isolates to the species level by using partial calmodulin and beta-tubulin gene sequencing and MALDI-TOF MS, and to evaluate their in vitro susceptibility to ten antifungal drugs: terbinafine, itraconazole, voriconazole, posaconazole, ravuconazole, isavuconazole, caspofungin, micafungin, anidulafungin and amphotericin B according to CLSI M38-A3. Our results indicate that A.flavus (n = 38, 79%) is the most common Aspergillus species causing onychomycosis in Mashhad, Iran. Other detected species were A. terreus (n = 3), A. tubingensis (n = 2), A. niger (n = 1), A. welwitschiae (n = 1), A. minisclerotigenes (n = 1), A. citrinoterreus (n = 1) and A. ochraceus (n = 1). Aspergillus flavus , A. terreus and A. niger isolates were correctly identified at the species level by MALDI-TOF MS, while all cryptic species were misidentified. In conclusion, A. flavus is the predominant Aspergillus species causing onychomycosis due to Aspergillus spp. in Mashhad, Iran. MALDI-TOF MS holds promise as a fast and accurate identification tool, particularly for common Aspergillus species. It is important that the current database of reference spectra, representing different Aspergillus species is expanded to increase the precision of the species-level identification. Terbinafine, posaconazole and echinocandins were i n vitro most active against the studies Aspergillus isolates and terbinafine could be the first choice for treatment of onychomycosis due to Aspergillus .
研究领域:
医学
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真菌学
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临床微生物学
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PubMed
高影响因子
MICROCHIMICA ACTA
·
2019
·Vol. 187
·期 1
·1-8
·
IF 5.479
Zhao Jie,Fan Zhefeng
A turn on–off fluorometric assay for clioquinol (CQ) is described here. It is based on modulation of the fluorescence of sulfur quantum dots (SQDs; best measured at excitation/emission wavelengths of 360/426 nm) by using the Zn 2+ -CQ affinity pair. Although the fluorescence enhancement effect of Zn 2+ on SQDs was not obvious, a good quenching modulation effect was observed in the presence of CQ. This resulted in a linear analytical range that is increased by two orders of magnitude (from 0.024 μM to 0.24 μM, and 0.62 μM to 30 μM), with a detection limit (3 s ) of 0.015 μM. The selectivity of the method is also improved.
Schematic illustration of the turn on-off fluorometric assay for for clioquinol (CQ) based on Zn 2+ -modulated sulfur quantum dots (SQDs).
研究领域:
分析化学
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药理学
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生物医学工程
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高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yiyang Li,Yannan Qin,Yi Liu,Bo Yuan,Zhirong Zhao,Jingyuan Wang,Yanhong Ji,Shuai Mao,Feng Ye,Chengcheng Liu,Chuanbin Mao
Onychomycosis is a prevalent nail infection caused by fungi, presenting significant treatment challenges due to poor drug penetration and high recurrence rates. Current treatments, including oral and topical antifungals, often have limited efficacy and can lead to resistance. Transfersomes are lipid vesicles that can penetrate skin for transdermal drug delivery. Here, a t ransfersome (termed THT) capable of penetrating nails to deliver a photosensitizer ( h ematoporphyrin monomethyl ether, HMME) and an antifungal chemotherapeutic drug ( t avaborole) has been developed, achieving a chemo-photodynamic synergistic treatment of onychomycosis. The optimized THT was prepared using a combination of soy lecithin, sodium deoxycholate, and cholesterol in an 8: 4: 0.5 ratio, with a particle size of 200 nm and a 30 % alcohol-water solvent system. This formulation significantly enhanced nail penetration, with the concentration of HMME reaching 330 times higher than that in phosphate-buffered saline. Moreover, THT showed potent fungicidal activity, reducing the survival of Trichophyton rubrum microconidia to as low as 3.24 % under light irradiation, and achieving approximately 90 % treatment efficacy in the ex vivo model. In addition to in vitro and ex vivo verification, an innovative rat onychomycosis model was established to confirm its superior therapeutic efficacy in vivo , with cure rates around 90 % and a significant reduction in fungal hyphae and spores. It is accumulated around and deformed to enter the physiological pores of the nail plate, effectively penetrating to deeper layers at the nail bed. THT, with its high nail penetration efficiency and potent synergistic antifungal activity, represents a promising topical treatment for onychomycosis.
研究领域:
药学
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微生物学
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生物医学工程
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皮肤病学
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PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Mengmin Liang,Qingwen Hu,Junhao Yu,Heng Zhang,Sijie Liu,Jiangrong Huang,Yi Sun
Background: Invasive fungal infections (IFIs) constitute a significant health challenge, particularly among immunocompromised individuals, characterized by a high prevalence and associated mortality rates. The synergistic administration of Baicalein (BE) with azole antifungal agents could potentially herald a novel therapeutic paradigm.Materials and methods: 54 Aspergillus strains and 23 strains of dematiaceous fungi were selected. The standard M38-A2 microbroth dilution method was used to test the minimum inhibitory concentration (MIC) and the fractional inhibitory concentration index (FICI) of fungi when BE combined with itraconazole (ITC), voriconazole (VRC), posaconazole (POS) and Isavuconazole (ISV).Results: BE shows synergistic effects with POS and ITC, with 89.61% and 25.97% of fungal strains. The BE/POS regimen exerted synergistic effects in 87.04% of Aspergillus and an impressive 95.65% of dematiaceous fungi. In comparison, the BE/ITC combination showed significantly lower synergy, affecting 33.33% of Aspergillus and a mere 8.70% of dematiaceous strains. Antagonistic interactions were sporadically observed with BE in combination with ITC, VRC, POS and ISV. Within the azole class, the BE/POS pairing stood out for its frequent synergistic activity, in contrast to the absence of such effects when BE was paired with VRC or ISV. Highlighting the potential of BE/POS as a notably effective antifungal strategy.Conclusion: In vitro, BE/POS combination emerged as the most effective antifungal strategy, exhibiting synergistic effects in the majority of Aspergillus and dematiaceous fungi strains, whereas BE/ITC showed significantly less synergy, and BE with VRC or ISV displayed no synergistic activity.
研究领域:
医学
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微生物学
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药理学
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PubMed
高影响因子
Acta Biomaterialia
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2022
·
IF 10.633
Guowei Li,Kai Lv,Xiangjun Pan,Siting Zhou,Hui Xing,Jun Xu,Dong Ma,Yunfeng Hu,Hao Xu
The low permeability of antifungal agents to fungal biofilms , which allows the continued survival of the fungus inside, is a key issue that makes fungal infections difficult to cure. Inspired by the unique dynamic molecule motion properties of the polyrotaxane (PR) nanomedicine , herein, a dynamic delivery system [email protected] /NONOate was fabricated by co-loading nitric oxide (NO) and the antifungal drug clotrimazole (Clo) onto the α-cyclodextrin (α-CD) PR modified mesoporous polydopamine (mPDA) nanoparticles , in which pentaethylenehexamine (PEHA) was grafted to α-CDs. The cationic α-CDs endowed this dynamic NO/Clo codelivery system with the ability to effectively attach to fungal biofilms through electrostatic interaction , while the introduction of PRs with flexible molecule motion (slide and rotation of CDs) enhanced the permeability of nanoparticles to biofilms. Meanwhile, NO could effectively inhibit the formation of fungal hyphae, showing an dissipating effect on mature biofilms, and could be further combined with Clo to completely eradicate fungi inside the biofilms. In addition, the dynamic system [email protected] /NONOate could efficiently and synergistically eliminate planktonic Candida albicans ( C. albicans ) in a safe and no toxic side effect manner, and effectively cured C. albicans -induced vaginal infection in mice. Therefore, this dynamic NO/Clo codelivery system provided an effective solution to the clinical treatment of C. albicans -induced vaginal infection, and the application prospect could even be extended to other microbial infectious diseases. Statement of significance A dynamic codelivery system based on cationized cyclodextrin polyrotaxane combining nitric oxide and antifungal drugs clotrimazole was prepared to deal with the issue of clinical fungal biofilm infection. This dynamic codelivery system could be attached to the Candida albicans biofilms and penetrate into biofilm via flexible molecular mobility to effectively eradicate the fungi. This dynamic codelivery system could synergistically and efficiently eliminate planktonic-state Candida albicans , but did not show significant cytotoxicity to normal somatic cells .
研究领域:
药学
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微生物学
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纳米医学
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高影响因子
Materials Chemistry Frontiers
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2020
·Vol. 4
·期 3
·957-964
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IF 6.788
Xiaoxue Ge,Meng Gao,Bo Situ,Weiwei Feng,Bairong He,Xiaojing He,Shiwu Li,Zihao Ou,Yiqi Zhong,Yahui Lin,Xinyi Ye,Xiumei Hu,Ben Zhong Tang,Lei Zheng
Fungi play key roles in various fields, including fermentation-based industries, medicine, and public health. The rapid and precise evaluation of fungal viability is critical for fungi-related fields. However, the methods currently applied have a series of limitations, such as time-consuming, laborious, and cumbersome. In this study, we designed and synthesized a water-dispersible fluorescent probe DPASI with typical aggregation-induced emission (AIE) characteristics for selectively lighting up dead Candida cells within 5 minutes. The rapid staining of the dead Candida cells could be ascribed to the efficient binding of DPASI with mitochondria, which was revealed by high-resolution fluorescence images taken by a structured illumination microscope (SIM) and colocalization images taken by a confocal laser scanning microscope (CLSM). Compared with traditional probes for the identification of dead Candida cells, the DPASI probe does not require tedious centrifugation and washing steps and has significant advantages in time-and-labor-saving. It thus provides a facile and promising tool for the rapid evaluation of antifungal susceptibility and screening of new antifungal drugs, which would greatly contribute to the fungal research.
研究领域:
微生物学
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医学检验
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药物研发
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2016
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IF 3.902
Baolin Wang,Hongxia Zheng,Ming-Wei Chang,Zeeshan Ahmad,Jing-Song Li
Hollow magnetic fibers for trigger based drug release were synthesized using one-step co-axial electrospinning (COX-ES). This was achieved by encapsulating the antifungal active ‘ketoconazole’ (KCZ) and iron oxide (Fe 3 O 4 ) nanoparticles (NPs) in composite form within the core shell polymeric matrix material (polycaprolactone, PCL) during the COX-ES process. Dimethyl silicone oil was used as the inner core (liquid) of co-flowing solutions, which subsequently perfused out of the two-phase electrospun microstructures to form hollow fibers. Resulting drug-loaded magnetic hollow fibers were characterized using optical microscopy, scanning electron microscopy and Fourier Transform Infra-Red. The tensile strength and magnetization properties of composite fibers were also assessed. KCZ drug concentration in electrospinning solutions strongly influenced resulting fiber morphology, drug loading efficiency and release. Expedited drug release during a slow-sustained phase was demonstrated through the application of an auxiliary magnetic field. Variations in tensile strength (∼1.3–6.3 MPa) were due to composite fiber components compromising polymer chain integrity. In-vitro cell studies (using human cervical carcinoma cell lines) demonstrated fiber biocompatibility. The present study demonstrates the potential application of magnetic hollow fibers for controlled treatment of fungal infections and antimicrobial indications.
研究领域:
材料科学
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药学
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生物医学工程
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高影响因子
BRAZILIAN JOURNAL OF MICROBIOLOGY
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2023
·Vol. 54
·期 4
·2597-2602
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IF 2.2
Zhang Meijie,Song Ge,Zheng Hailin,Pathakumari Balaji,Liu Weida,Liang Guanzhao
Purpose Since systematic antifungals for mucormycosis showed variable MICs depending on strains, effective and safe antifungal therapy was still needed. This study is aimed to evaluate the in vitro activity of doxycycline combined with antifungal therapy against dominant Mucorales pathogens. Methods Multidrug susceptibility testing was performed with doxycycline and antifungals, including itraconazole, posaconazole, and amphotericin, in 21 isolates of 8 dominant Mucorales pathogens. Results The fractional inhibitory concentration index according to M38 showed one Rhizopus arrhizus isolate synergic ( ∑ FICI = 0.375) and other isolates in addition (0.5 < ∑ FICI < 4). Conclusions Doxycycline was found to have in vitro advantages in combined antifungal treatment over antifungals alone.
研究领域:
医学
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微生物学
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PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
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2025
·Vol. 48
·期 5
·e70172
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IF 2.8
Wenyang Hu,Hongxia Liu
Deep eutectic solvents have attracted increasing attention in enantioseparation, but only a few studies focus on the development of deep eutectic solvents as the sole chiral selector. In this work, a one-pot synthetic method was used to prepare a deep eutectic solvent based on a polysaccharide chiral selector (maltodextrin) as the sole chiral selector in capillary electrophoresis. Six azole antifungal drugs were used as model drugs to investigate the chiral resolution ability of the maltodextrin-glycerol. Compared to native maltodextrin, the deep eutectic solvents exhibited the more excellent enantioselectivity towards model drugs. Some key factors affecting separation such as maltodextrin concentration, glycerol concentration, buffer pH and separation voltage were investigated. In addition, ultraviolet spectroscopy method and Statistical Product and Service Solutions analysis were adopted to investigate the enhanced chiral recognition mechanism. It is the first time that polysaccharide-based deep eutectic solvents was developed as a favorable chiral selector in capillary electrophoresis, and this research strategy has paved a new way for developing novel chiral materials.
研究领域:
分析化学
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药物化学
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高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2022
·
IF 3.841
Meng-Yao Wu,Fan-Zhi Bu,Yu Yu,Yue-Ming Yu,Zhi-Yong Wu,Cui-Wei Yan,Yan-Tuan Li
To highlight the preponderance of excipients maleic acid (MA) and fumaric acid (FA) in perfecting physicochemical peculiarities of antifungal drug econazole (ENZ), furthermore get some innovative cognitions on the regulation of solid crystalline form and antifungal activity of ENZ through regioisomers of unsaturated aliphatic dicarboxylic acids, two novice crystalline complexes of ENZ involving one cocrystal with FA, ENZ-FA ( 1 ), and one molecular salt with MA, ENZ-MA ( 2 ), are gained and structurally identified. The single-crystal X-ray diffraction analysis confirms that the component ratios of 2:1 and 1:1 for ENZ and corresponding acid molecules severally in 1 and 2 . Both the cocrystallized solids have sandwich layer structures with hydrophobic surfaces and hydrophilic inner supramolecular networks with varied supramolecular aggregates, resulting in the simultaneous increasement in their dissolubility and permeability, thereinto, 1 owns higher permeability, while 2 is more ascendent in dissolubility, which are demonstrated by the combination of theory with experiment approaches. Specifically, compared with parent drug ENZ, the optimized physicochemical properties have endowed these cocrystallized complexes with strengthened in vitro antifungal activities, displaying larger inhibition rings and smaller MIC values, comparatively, 2 showcases stronger antifungal ability than that of 1 . All the outcomes supply different molecular crystalline solids for ENZ, and fill the gap of its cocrystal investigations.
研究领域:
药学
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晶体化学
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高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2023
·Vol. 76
·期 2
·115-121
·
IF 3.3
Ye Zhongjiang,Wang Chenxiang,Li Rongqi,Chen Chuang,Yang Jianhui,Chen Yizhang,Fu Jing,Zhou Tao,Jin Mi,Huang Aifang,Zhang Xiuhua,Zhou Ziye
AimOur study is to investigate the effects of triazole antifungal drugs on the pharmacokinetics of lorlatinib in rats.MethodsThe samples were precipitated with methanol. Chromatographic separation was performed on a ultra-performance liquid chromatography (UPLC) system using a BEH C18 column. The mobile phase consisted of 0.1% formic acid water and methanol. Lorlatinib and crizotinib (internal standard) were detected in multiple reaction monitoring mode. The fragment ions were 407.3–228.07 for lorlatinib and m/z 450.3–260.0 for crizotinib. Lorlatinib and different triazole antifungal drugs were given to Sprague Dawley rats by gavage, and blood was collected from the tail vein at a certain time point. The validated UPLC–MS/MS method was applied to a drug interaction study of ketoconazole, voriconazole, itraconazole, and posaconazole with lorlatinib in rats.ResultsKetoconazole and voriconazole significantly inhibited lorlatinib metabolism. When administration with ketoconazole and voriconazole, the area under the curve from time zero to infinity of lorlatinib increased by 49.0% and 104.3%, respectively; the clearance decreased by 40.0% and 40.0%, respectively. While itraconazole and posaconazole did not affect lorlatinib pharmacokinetics.ConclusionThe UPLC-MS/MS-based assay is helpful to further understand the pharmacokinetics of lorlatinib in rats, and confirmed the findings that the combination of lorlatinib with CYP3A inhibitors should be avoided as predicted by our pre-clinical studies.
研究领域:
药理学
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分析化学
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临床药学
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PubMed
高影响因子
Pharmaceuticals
·
2023
·Vol. 16
·期 11
·1537
·
IF 4.6
Wenjing Li,Yang Li,Junlong Cai,Yue Wang,Yanan Liu,Hankun Hu,Liang Liu
Systemic antifungal agents are essential for high-risk patients undergoing immunosuppressive therapy or cancer chemotherapy because of the rapid increase in opportunistic fungal infections. Therapeutic drug monitoring is crucial to ensuring the efficacy and safety of antifungal agents owing to their pharmacokinetic variability. In the present study, we developed and validated a quantitative method for the simultaneous detection of seven commonly used antifungal drugs (amphotericin B, isavuconazole, voriconazole, fluconazole, posaconazole, caspofungin, and micafungin) using liquid chromatography-tandem mass spectrometry. Methanol (containing 0.1% formic acid) was used for protein precipitation and only 50 μL of serum was required for the analysis. Chromatographic separation was conducted using a Waters Acquity UPLC C8 column, and one stable isotope-labeled agent and two analogs were used as internal standards. The calibration curves ranged from 0.1 to 50 μg/mL for all agents, and the correlation coefficient (R2) for all calibration curves was above 0.9835. The intra-day precision (1.2–11.2%), inter-day precision (2.4–13.2%), and mean bias values (−10.9 to 13.6%) were within an acceptable range of ±15%. Successful implementation of the developed method in clinical practice would facilitate the effective monitoring of these antifungal agents.Keywords:antifungal agents;therapeutic drug monitoring;LC–MS/MS;simultaneous quantitation;human serum
研究领域:
药理学
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临床医学
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分析化学
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PubMed
高影响因子
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