Selective Antimicrobial Effects of Curcumin@Halloysite Nanoformulation: A Caenorhabditis elegans Study

Abstract

Alterations in the normal gastrointestinal microbial community caused by unhealthy diet, environmental factors, and antibiotic overuse may severely affect human health and well-being. Novel antimicrobial drug formulations targeting pathogenic microflora while not affecting or even supporting symbiotic microflora are urgently needed. Here we report fabrication of a novel antimicrobial nanocontainer based on halloysite nanotubes loaded with curcumin and protected with a dextrin outer layer (HNTs+Curc/DX) and its effective use to suppress the overgrowth of pathogenic bacteria in Caenorhabditis elegans nematodes. Nanocontainers have been obtained using vacuum-facilitated loading of hydrophobic curcumin into halloysite lumens. We have applied UV–vis and infrared spectroscopy, thermogravimetry and microscopy to characterize the HNTs+Curc/DX nanocontainers. In experiments in vitro we found that HNTs+Curc/DX effectively suppressed the growth of Serratia marcescens cells, whereas Escherichia coli bacteria were not affected. We applied HNTs+Curc/DX nanocontainers to alleviate the S. marcescens infection in C. elegans nematodes in vivo. The nematodes ingest HNTs+Curc/DX at 4–6 ng per worm, which results in improvement of the nematodes’ fertility and life expectancy. Remarkably, treatment of S. marcescens-infected nematodes with HNTs+Curc/DX nanocontainers completely restored the longevity, demonstrating the enhanced bioavailability of hydrophobic curcumin. We believe that our results reported here open new avenues for fabrication of effective antimicrobial nanoformulations based on hydrophobic drugs and clay nanotubes.

Facile Fabrication of Natural Polyelectrolyte-Nanoclay Composites: Halloysite Nanotubes, Nucleotides and DNA Study

“…Safety is obligatory for biomedical materials, thus using non-toxic components such as clay nanotubes and DNA is advantageous for creating novel materials intended for being in contact with living matter. Low toxicity of halloysite nanotubes for prokaryotic and eukaryotic organisms was repeatedly shown [24,71,[87][88][89][90]. Here, evaporation induced self-assembly of DNA-Mg-modified halloysite nanotubes yielded a complex pattern similar to those previously obtained from pristine [42] or PSS-modified nanotubes [43], however, the pattern obtained from DNA-Mg-modified halloysite was more spiral-like rather than simply concentric.…”

“…As halloysite nanotubes are suggested as vectors for oral nucleic acid delivery, testing of halloysite behaviour under simulated gastric environments is also required. In vivo studies demonstrated that oral delivery of an antimicrobial nanocontainer based on halloysite nanotubes loaded with curcumin and protected with a dextrin outer layer was effective in selective suppression of the overgrowth of pathogenic bacteria in Caenorhabditis elegans nematodes [24]. The release kinetics of the anticancer drug paclitaxel encapsulated in halloysite coated with the pH-responsive polymer poly(methacrylic acid-co-methyl methacrylate was evaluated in simulated gastric and intestinal conditions, and a triggered drug release pattern was observed [22].…”

“…The halloysite nanotubes can be further modified to change their charge, colloid stability, lumen size [16] or rendering them stimuli-responsive [20]. Halloysite nanotubes have also been used as nanocontainers for delivery of antimicrobial dyes [21], paclitaxel [22], curcumin [23,24], antibiotics [25] and cell labeling agents [26]. Recently, the use of halloysite nanotubes-carbon dots hybrids as non-viral vectors for oral gene delivery was proposed [27].…”

Naturally derived nano- and micro-drug delivery vehicles: halloysite, vaterite and nanocellulose

“…53 Recent in vivo studies confirmed the potential of HNTs as effective drug delivery containers, showing that treatment with curcumin-loaded HNTs suppresses the growth of pathogenic bacteria in C. elegans and completely restores the longevity of infected nematodes. 54 An in vivo study of pharmacokinetics revealed that an orally administered suspension of fluorescently labelled HNTs is not absorbed by the intestines and eliminated via feces within one day, while systemically administered nanotubes are eliminated via urine/feces within nearly 72 h. 55 Notably, although in this study and some other studies 23 HNTs are intravenously injected, HNTs are non-biodegradable in blood. Indeed, recent studies have not recommended direct injections of HNTs that may lead to a thrombosis.…”

Antibacterial properties and in vivo studies of tannic acid-stabilized silver–halloysite nanomaterials

“…Nemotodes, both free living and parasitic, have been studied extensively due to their biological diversity and effects on human well-being and agriculture. Nematodes have been successfully employed as versatile model organisms in previous investigations by the present authors (Fakhrullina et al, 2015(Fakhrullina et al, , 2017(Fakhrullina et al, , 2019Akhatova et al, 2018). Use of the C. elegans nematode, as a typical and perhaps the most studied model organism, is extremely popular in biomedicine and nanoscience.…”