Abstract
More than 150 million people have significant fungal diseases that greatly impact health care and economic expenditures. The expansion of systemic fungal infections and invasive mycoses is being driven by an increase in the number of immunocompromised patients and the recent COVID-19 patients, especially severely ill. There have been numerous cases of fungal infections linked to COVID-19, with pulmonary aspergillosis dominating at first but with the subsequent appearance of mucormycosis, candidiasis, and endemic mycoses. Candida spp. is the most frequent pathogen, with approximately 1 billion infections yearly, among other species causing the most prevalent invasive fungal infections. The importance of recognizing the epidemiological shifts of invasive fungal infections in patient care cannot be overstated. Despite the enormous antifungal therapies available, these infections are difficult to diagnose and cause high morbidity and mortality rates. Treatment choices for systemic fungal infections are severely limited due to the limitations of conventional therapy effectiveness and drug toxicities. So the researchers are still looking for novel therapeutic options, such as carrier-based approaches that are convenient and cost-effective with high and long-lasting fungal infection cure rates with reduced toxicities. The focus of this study is on summarizing the nanotechnology, immunotherapy methods and the drugs under clinical trials that have been employed in treatment as carrier-based antifungal formulations. Most of these have been reported to be promising strategies with broad-spectrum antifungal action and the potential to overcome antibiotic resistance mechanisms. We speculate that this review summarized the current knowledge to its best that will help the future developments of new antifungal therapies.
Graphical Abstract
[http://dx.doi.org/10.3390/jof3040057] [PMID: 29371573]
[http://dx.doi.org/10.1007/978-1-4939-6515-1_5]
[http://dx.doi.org/10.3390/antibiotics9080445] [PMID: 32722455]
[http://dx.doi.org/10.1017/S0022215121000992] [PMID: 33827722]
[http://dx.doi.org/10.1016/j.resmic.2021.103915] [PMID: 34863883]
[http://dx.doi.org/10.1016/j.ijantimicag.2019.01.002] [PMID: 30639526]
[http://dx.doi.org/10.1592/phco.23.14.1441.31938] [PMID: 14620391]
[http://dx.doi.org/10.2147/TCRM.S40160] [PMID: 24611015]
[http://dx.doi.org/10.1016/bs.mim.2015.05.002]
[http://dx.doi.org/10.3389/fmicb.2017.00336] [PMID: 28326065]
[http://dx.doi.org/10.1016/j.ijpharm.2017.03.019] [PMID: 28323096]
[http://dx.doi.org/10.1002/lsm.23180] [PMID: 31746024]
[http://dx.doi.org/10.1016/j.biopha.2018.12.009] [PMID: 30557835]
[http://dx.doi.org/10.1111/1523-1747.ep12478053] [PMID: 1107433]
[http://dx.doi.org/10.1128/JB.183.18.5385-5394.2001] [PMID: 11514524]
[http://dx.doi.org/10.1099/jmm.0.46548-0] [PMID: 16772406]
[http://dx.doi.org/10.1086/421946] [PMID: 15306996]
[http://dx.doi.org/10.1086/500405] [PMID: 16477560]
[http://dx.doi.org/10.1086/339202] [PMID: 11880955]
[http://dx.doi.org/10.1086/322606] [PMID: 11486286]
[http://dx.doi.org/10.1182/blood-2002-05-1496] [PMID: 12393425]
[http://dx.doi.org/10.1016/S1473-3099(17)30443-7] [PMID: 28774697]
[http://dx.doi.org/10.1111/j.1469-0691.2010.03288.x] [PMID: 20840541]
[http://dx.doi.org/10.1128/AAC.01504-09] [PMID: 20145078]
[http://dx.doi.org/10.1086/591861] [PMID: 18947320]
[http://dx.doi.org/10.1086/499811] [PMID: 16421795]
[http://dx.doi.org/10.1086/520192] [PMID: 10476719]
[http://dx.doi.org/10.1016/j.jhin.2006.02.014] [PMID: 16713019]
[http://dx.doi.org/10.1016/j.ccm.2009.02.009] [PMID: 1937563]
[http://dx.doi.org/10.1111/j.1469-0691.2008.01978.x] [PMID: 18430126]
[http://dx.doi.org/10.1016/S0891-5520(02)00068-5] [PMID: 12751265]
[http://dx.doi.org/10.1016/j.riam.2009.06.003] [PMID: 19836985]
[http://dx.doi.org/10.1093/jac/46.2.171] [PMID: 10933638]
[http://dx.doi.org/10.1016/j.idc.2015.10.012] [PMID: 26739608]
[http://dx.doi.org/10.1128/AAC.43.8.1955] [PMID: 10428919]
[http://dx.doi.org/10.1111/j.1439-0507.2009.01805.x] [PMID: 19878457]
[PMID: 21694908]
[http://dx.doi.org/10.1093/cid/civ571] [PMID: 26179012]
[http://dx.doi.org/10.1039/C3NP70070D] [PMID: 24270605]
[http://dx.doi.org/10.1016/j.tim.2010.02.004] [PMID: 20207544]
[PMID: 10066533]
[http://dx.doi.org/10.1056/NEJMoa020191] [PMID: 12167683]
[http://dx.doi.org/10.1086/525258] [PMID: 18177225]
[http://dx.doi.org/10.1513/pats.200906-048AL] [PMID: 20463252]
[http://dx.doi.org/10.1016/S0966-842X(03)00117-3] [PMID: 12823944]
[http://dx.doi.org/10.5694/j.1326-5377.2007.tb01313.x] [PMID: 17908006]
[http://dx.doi.org/10.1007/978-1-4612-2762-5_6] [PMID: 1732066]
[PMID: 22043144]
[http://dx.doi.org/10.1016/j.ijpharm.2020.119780] [PMID: 32860856]
[http://dx.doi.org/10.1016/j.jcis.2014.09.023] [PMID: 25310578]
[http://dx.doi.org/10.1016/j.ijpharm.2017.04.013] [PMID: 28400291]
[http://dx.doi.org/10.1016/j.ijpddr.2018.04.001] [PMID: 29673889]
[http://dx.doi.org/10.1016/j.apsb.2021.04.010] [PMID: 34522599]
[http://dx.doi.org/10.1111/j.1469-0691.2001.tb00012.x] [PMID: 11525221]
[http://dx.doi.org/10.1016/j.ijpharm.2010.07.003] [PMID: 20621173]
[http://dx.doi.org/10.1016/j.ejps.2009.02.021] [PMID: 19491021]
[PMID: 24379661]
[PMID: 25473279]
[http://dx.doi.org/10.1016/j.jconrel.2012.05.037] [PMID: 22641062]
[http://dx.doi.org/10.1186/s11671-015-0969-1] [PMID: 26061446]
[http://dx.doi.org/10.1021/mp500527x] [PMID: 25558881]
[http://dx.doi.org/10.2147/IJN.S17503] [PMID: 21720503]
[http://dx.doi.org/10.2147/IJN.S84656] [PMID: 26491294]
[http://dx.doi.org/10.1371/journal.pntd.0004754] [PMID: 27303789]
[PMID: 25784804]
[http://dx.doi.org/10.1016/j.ijpharm.2005.05.027] [PMID: 16023808]
[http://dx.doi.org/10.1016/j.colsurfb.2016.03.013] [PMID: 26974361]
[http://dx.doi.org/10.1016/j.colsurfb.2018.12.011] [PMID: 30579053]
[http://dx.doi.org/10.3109/02652048.2012.714410] [PMID: 22894166]
[PMID: 25733833]
[http://dx.doi.org/10.1016/j.jddst.2018.02.014]
[http://dx.doi.org/10.1016/j.nano.2012.04.005] [PMID: 22633899]
[http://dx.doi.org/10.1016/j.ijpharm.2007.10.009] [PMID: 18053659]
[http://dx.doi.org/10.1080/10717544.2018.1492046] [PMID: 30044149]
[http://dx.doi.org/10.1038/nrd3074] [PMID: 20725094]
[http://dx.doi.org/10.1093/jac/49.suppl_1.31] [PMID: 11801578]
[http://dx.doi.org/10.1093/jac/dkl005] [PMID: 16446374]
[http://dx.doi.org/10.1128/AAC.50.2.674-684.2006] [PMID: 16436726]
[http://dx.doi.org/10.1016/j.nano.2016.07.006] [PMID: 27464757]
[http://dx.doi.org/10.1007/s11095-016-2062-6] [PMID: 27928646]
b) Das PJ, Paul P, Mukherjee B. Mazumder B, Mondal L, Baishya R, Debnath MC, Dey KS Pulmonary delivery of voriconazole loaded nanoparticles providing a prolonged drug level in lungs: a promise for treating fungal infection. Mol Pharm 2015; 12(8): 2651-64.
[PMID: 25941882]
[http://dx.doi.org/10.1007/s12281-014-0185-y]
[http://dx.doi.org/10.1016/j.mycmed.2020.101007] [PMID: 32718789]
[http://dx.doi.org/10.1016/j.ijantimicag.2021.106291] [PMID: 33508404]
[http://dx.doi.org/10.3389/fcimb.2020.00469] [PMID: 33042859]
[http://dx.doi.org/10.1016/j.biopha.2020.110550] [PMID: 32739740]
[http://dx.doi.org/10.1016/S1473-3099(17)30442-5] [PMID: 28774700]
[http://dx.doi.org/10.1016/j.cyto.2008.03.002] [PMID: 18400509]
[http://dx.doi.org/10.1093/infdis/jit574] [PMID: 24163416]
[http://dx.doi.org/10.1016/j.biopha.2018.10.075] [PMID: 30399567]
[http://dx.doi.org/10.1016/S1201-9712(02)90104-9] [PMID: 12718828]
[http://dx.doi.org/10.1590/0074-02760150335] [PMID: 26602871]
[http://dx.doi.org/10.1002/phar.1652] [PMID: 26598096]
[http://dx.doi.org/10.1016/j.jgar.2018.02.013] [PMID: 29486356]
[http://dx.doi.org/10.1590/S0074-02762011000200022] [PMID: 21537689]
[http://dx.doi.org/10.3390/jof6030122] [PMID: 32751765]
[http://dx.doi.org/10.1038/nrd.2017.46] [PMID: 28496146]
[http://dx.doi.org/10.1093/cid/ciaa1204] [PMID: 32818963]
[http://dx.doi.org/10.1128/AAC.05954-11] [PMID: 22948882]
[http://dx.doi.org/10.1093/jac/dkv398] [PMID: 26620102]
[http://dx.doi.org/10.3389/fmed.2021.670731] [PMID: 33968970]
[http://dx.doi.org/10.1128/AAC.00349-16] [PMID: 27161631]