<p>Potential of Methylglyoxal-Conjugated Chitosan Nanoparticles in Treatment of Fluconazole-Resistant <em>Candida albicans</em> Infection in a Murine Model</p>

Abstract

Background: Fungal infections are becoming more prevalent and threatening because of the continuous emergence of azole-resistant fungal infections. The present study was aimed to assess the activity of free Methylglyoxal (MG) or MG-conjugated chitosan nanoparticles (MGCN) against fluconazole-resistant Candida albicans. Materials and Methods: A novel formulation of MGCN was prepared and characterized to determine their size, shape and polydispersity index. Moreover, the efficacy of fluconazole or MG or MGCN was determined against intracellular C. albicans in macrophages and the systematic candidiasis in a murine model. The safety of MG or MGCN was tested in mice by analyzing the levels of hepatic and renal toxicity parameters. Results: Candida albicans did not respond to fluconazole, even at the highest dose of 20 mg/kg, whereas MG and MGCN effectively eliminated C. albicans from the macrophages and infected mice. Mice in the group treated with MGCN at a dose of 10 mg/kg exhibited a 90% survival rate and showed the lowest fungal load in the kidney, whereas the mice treated with free MG at the same dose exhibited 50% survival rate. Moreover, the administration of MG or MGCN did not induce any liver and kidney toxicity in the treated mice. Conclusion: The findings of the present work suggest that MGCN may be proved a promising therapeutic formulation to treat azole-resistant C. albicans infections.

Coadministration of Ginger Extract and Fluconazole Shows a Synergistic Effect in the Treatment of Drug-Resistant Vulvovaginal Candidiasis

“…The in vitro activity of FLZ or Meth-Gin or a combination of FLZ and Meth-Gin was determined by the agar well diffusion and macrodilution methods. 8 C. albicans was seeded on the SDA plates and the holes of 8 mm diameter were made to load 100 µL of FLZ (100 µg) or Meth-Gin (500 µg) or FLZ (100 µg) + Meth-Gin (250 µg) and FLZ (100 µg) + Meth-Gin (500 µg). The plates were incubated at 37 °C for 24 hours and the zone of growth inhibition was measured.…”

“… 40 The levels of the blood urea nitrogen (BUN) and creatinine were determined to investigate the toxic effects of the treatment on kidney. 8 …”

“… 6 Moreover, azoles also increase the reactive oxygen species (ROS) levels in the fungal biofilm. 7 But their extensive use has resulted in the emergence of azole-resistant Candida isolates 8 , 9 Besides attempting to search the new antifungal chemotherapeutics, the rejuvenation of the existing antifungal drugs also becomes important to compensate the depleted armory of the antifungal drugs. 10 The use of antibiotic combinations seems to be an important strategy to counter the phenomenon of drug resistance.…”

Current applications and prospects of nanoparticles for antifungal drug delivery

“…Khan and his colleagues (2020) synthesized Methylglyoxal Chitosan Nanoparticles (MGCN) against fluconazole-resistant Candida albicans and investigated them both in vitro and in a mouse model. Synthesized NPs not only evinced higher intracellular killing of Candida albicans in infected macrophages of female BALB/C mice, but also inhibited yeast to hyphae transition, and enhanced in vivo efficacy and reduced toxicity (Khan et al, 2020[ 58 ]).…”

“…All studies are summarized in Table 1 (Tab. 1) (References in Table 1: Ahmad et al, 2016[ 2 ]; Ahmed and Aljaeid, 2017[ 3 ]; Ahsan and Rao, 2017[ 4 ]; Aljaeid and Hosny, 2016[ 7 ]; Amaral et al, 2010[ 8 ]; Anurak et al, 2011[ 10 ]; Bhalekar et al, 2009[ 17 ]; Butani et al, 2016[ 22 ]; Cassano et al, 2016[ 24 ]; Chandasana et al, 2014[ 25 ]; Chhonker et al, 2015[ 27 ]; Das et al, 2015[ 32 ]; El-Housiny et al, 2018[ 35 ]; Fu et al, 2017[ 43 ]; Füredi et al, 2017[ 44 ]; Gupta et al, 2013[ 47 ]; Hussain et al, 2019[ 55 ]; Jain et al, 2010[ 56 ]; Kenechukwu et al, 2017[ 57 ]; Khan et al, 2020[ 58 ]; Kumar and Sinha, 2016[ 60 ]; Liu et al, 2014[ 64 ]; Lucena et al, 2018[ 66 ]; Mohammed et al, 2013[ 71 ]; Mohanty et al, 2015[ 72 ]; Muñoz-Escobar and Reyes-López 2020[ 76 ]; Mussin et al, 2019[ 78 ]; Niemirowicz et al, 2016[ 81 ]; Pandey et al, 2005[ 85 ]; Paul et al, 2018[ 86 ]; Radwan et al, 2017[ 91 ]; Sandhya et al, 2018[ 98 ]; Sangeetha et al, 2007[ 99 ]; Sanna et al, 2007[ 100 ]; Song et al, 2013[ 103 ]; Souto et al, 2004[ 104 ]; Souza et al, 2015[ 105 ]; Szerencsés et al, 2020[ 109 ]; Thakur et al, 2019[ 112 ]; Tutaj et al, 2016[ 116 ]; Vásquez Marcano et al, 2018[ 117 ]; Xu et al, 2014[ 120 ]).…”