Abstract
As the second wave of COVID-19 hits South Asia, an increasing deadly complication ‘fungal infections (such as Mycosis, Candida and Aspergillus) outbreak’ has been raised concern about the insufficient technologies and medicals for its diagnosis and therapy. Biosilica based nano-therapy can be used for therapeutic efficacy, yet their direct role as antibiotic agent with biocompatibility and stability remains unclear. Here, we report that a diatomaceous earth (DE) framework semiconductor composite conjugated DE and in-house synthesized zinc oxide (DE-ZnO), as an antibiotic agent for the enhancement of antibiotic efficacy and persistence. We found that the DE-ZnO composite had enhanced antibiotic activity against fungi (A. fumigatus) and Gram-negative bacteria (E. coli, S. enterica). The DE-ZnO composite provides enhancing large surface areas for enhancement of target pathogen binding affinity, as well as produces active ions including reactive oxygen species and metal ion for breaking the cellular network of fungi and Gram-negative bacteria. Additionally, the toxicity of DE-ZnO with 3 time less amount of dosage is 6 times lower than the commercial SiO2-ZnO. Finally, a synergistic effect of DE-ZnO and existing antifungal agents (Itraconazole and Amphotericin B) showed a better antifungal activity, which could be reduced the side effects due to the antifungal agents overdose, than a single antibiotic agent use. We envision that this DE-ZnO composite can be used to enhance antibiotic activity and its persistence, with less-toxicity, biocompatibility and high stability against fungi and Gram-negative bacteria which could be a valuable candidate in medical science and industrial engineering.
Highlights
The recent BBC report showing that those who have been cared in intensive care unit (ICU) of severe COVID-19 are vulnerable to deadly infections [1,2,3,4]
3.1 Synthesis and characterization of diatomaceous earth (DE)‐zinc oxide (ZnO) First, in order to synthesize Synthesized ZnO nanomaterial (ZnO-S) (~ 300 nm) through facile hydro-thermal method (Fig. 1A), we optimized the one-pot method which reduce the cost of synthesis production using the zinc contains with 98% SiO2
Through Barrett-Joyner-Halenda (BJH) pore size and volume analysis (Additional file 1: Fig. S1D–F), the mild manufacturing process used for ZnO-S synthesis was optimized to obtain uniform ZnO-S, and the morphology of the ZnO-S was built by nanoparticles (3 ~ 7 nm), which implied that there is a large surface area
Summary
The recent BBC report showing that those who have been cared in intensive care unit (ICU) of severe COVID-19 are vulnerable to deadly infections [1,2,3,4]. In comparison with the death rate of COVID-19 (about 2.1%, calculate by 28th June, 2021), the high fatality rate of these Invasive Aspergillosis infection (IAI, such as mycosis: 70%, candida: 25%, aspergillus: 30 ~ 90%) has sent people into. The treatment of IAI caused by Aspergillus fumigatus, Candida albicans, and C. glabrata are constrained due to the toxicity of the agents, drug resistance, and low efficacy. Drugs with antifungal activity that are used to treat patients with IAI are azoles, polyenes, and echinocandins [17]. Among these drugs, amphotericin B is one of polyenes, used to break the membrane of fungi by binding with ergosterol, which subsequently leads to cell death. There is an urgent demand to find better solution, which could have enhanced efficacy and persistence with relatively less toxicity [22]
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