Oleic Acid Coated Silver Nanoparticles Showed Better in Vitro Amoebicidal Effects against Naegleria fowleri than Amphotericin B

Abstract

Naegleria fowleri (N. fowleri) causes primary amoebic meningoencephalitis (PAM) which almost always results in death. N. fowleri is also known as “brain-eating amoeba” due to its literal infestation of the brain leading to an inflammatory response in the brain tissues. Currently, there is no single drug that is available to treat PAM, and most treatments are combinations of antifungal, anticancer, and anti-inflammatory drugs. Recently nanotechnology has gained attention in chemotherapeutic research converging on drug delivery, while oleic acid (OA) has shown positive effects on the human immune system and inflammatory processes. In continuation of our recent research in which we reported the effects of oleic acid conjugated with silver nanoparticles (OA-AgNPs) against free-living amoeba Acanthamoeba castellanii, in this report, we show their antiamoebic effects against N. fowleri. OA alone and its nanoconjugates were tested against the amoeba by using amoebicidal and host cell cytopathogenicity assays. Trypan blue exclusion assay was used to determine cell viability. The results revealed that OA-AgNPs exhibited significantly enhanced antiamoebic effects (P < 0.05) against N. fowleri as compared to OA alone. Evidently, lactate dehydrogenase release shows reduced N. fowleri-mediated host cell cytotoxicity. Based on our study, we anticipate that further studies on OA-AgNPs could potentially provide an alternative treatment of PAM.

Metronidazole conjugated magnetic nanoparticles loaded with amphotericin B exhibited potent effects against pathogenic Acanthamoeba castellanii belonging to the T4 genotype

“…The synthesized nano carrier was screened for its cytotoxicity using MTT assay. Human cervical adenocarcinoma cells (HeLa) (ATCC ® CCL-2™), were obtained from American Type Culture Collection (ATCC),and cultured in Roswell Park Memorial Institute (RPMI) 1640 medium, supplemented with 10% foetal bovine serum, 1% minimum essential medium amino acids, 1% l -glutamine and 1% antibiotics at 37 °C with 5% CO 2 (Rajendran et al 2019 ). NIH 3T3 cells (ATCC CRL-1658) were purchased from the ATCC and cultured in Dulbecco`s modified eagle`s medium (DMEM) having foetal bovine serum (10%) (Invitrogen, USA) and antibiotics (streptomycin and penicillin—about 50 U/mL).Both cell lines were incubated into well plates with 96 wells and 8 × 10 3 and 6 × 10 4 cells/well thickness, individually, in a (200 µL) refined media.…”

“…Amoebicidal assays were performed as previously described (Rajendran et al 2019 ). Briefly, 5 × 10 5 amoebae were incubated with compounds at various concentrations for 24 h at 30 °C.…”

Primary Amoebic Meningoencephalitis by Naegleria fowleri: Pathogenesis and Treatments

“…In more recent years, nanoparticles have gained attention in the pharmaceutical industry for their ability to enhance the efficacy of a drug, which allows a decrease in dosage [ 63 ]. Since nanoparticle drug delivery systems have been demonstrated to increase bioavailability, decrease cell toxicity, and are site-specific, there have been a few studies determined to understand the advantages of using drugs conjugated with nanoparticles to treat PAM ( Table 3 ) [ 80 ].…”

“…The study concluded that 10 µM of OA-AgNp was able to reduce the number of N. fowleri from 6.1 × 10 5 to 2.1 × 10 5 . This conjugation exhibited higher activity against the trophozoites than AmB, which reduced the amoeba to 2.7 × 10 5 [ 80 ]. Another study investigated the conjugation of three different FDA-approved drugs to reduce the number of N. fowleri trophozoites.…”

Think Big, Start Small: How Nanomedicine Could Alleviate the Burden of Rare CNS Diseases

“…More recently, a follow-up study from the same group looked at the effect of oleic acid-coated silver nanoparticles (OA-AgNPs) with a mean diameter comprised between 45 and 90 nm against N. fowleri [119]. OA is a naturally occuring monounsaturated omega-9 fatty acid, which has been associated with health benefits, such as hypotensive or anti-inflammatory effects; it also exhibited potent antiacanthamoebic activity against Acanthamoeba castellanii [120,121].…”