Abstract
The establishment of an effective therapeutic agent against Acanthamoeba keratitis (AK), remains until present, an issue to be solved due to the existence of a cyst stage in the life cycle of Acanthamoeba. Moreover, the effectiveness of the current standard therapeutic agents varies depending on the tested Acanthamoeba strains and its resistance pattern. In the present study, two 10-point augmented simplex-centroid designs were used to formulate a three-component mixture system using water, atorvastatin, and Diclofenaco-lepori or Optiben. The amoebicidal effects and in vitro-induced toxicity in a eukaryotic cell line were determined for all experiments. The optimal mixture to inhibit the parasite without inducing toxicity was established in the first plan as 30% Optiben, 63.5% atorvastatin, and 3.1% water. As for the second experimental design, the optimal mixture to inhibit Acanthamoeba with lower toxicity effect was composed of 17.6% Diclofenaco-lepori and 82.4% atorvastatin.
Highlights
Acanthamoeba, a member of the free-living amoeba group, is a ubiquitous protist and opportunistic parasite that has been isolated from different habitats, such as soil, water, air, dust, drinking water, sea water, and recreational water [1,2,3]
A 10-point augmented simplex-centroid design was used to formulate three-component mixture systems comprised of atorvastatin, Optiben, and water (Table 1)
As for the Acanthamoeba growth, we report the existence of synergy between the D-L and atorvastatin
Summary
Acanthamoeba, a member of the free-living amoeba group, is a ubiquitous protist and opportunistic parasite that has been isolated from different habitats, such as soil, water, air, dust, drinking water, sea water, and recreational water (home aquaria, swimming pools) [1,2,3]. The treatment of Acanthamoeba infections consists of a combination of biguanides, amidines, and azoles. This therapeutic regimen has limited efficacy due to the toxicity of the drugs, the requirement for long-term treatment, variable efficacy between strains or species, and Pathogens 2020, 9, 219; doi:10.3390/pathogens9030219 www.mdpi.com/journal/pathogens. 2020, 9, 219the treatment of Acanthamoeba infections consists of a combination of biguanides, amidines, and azoles This therapeutic regimen has limited efficacy due to the toxicity of the drugs, the requirement for long-term treatment, variable efficacy between strains or species, and the presence of a resistant cyst form. Recent advances reported by our group have highlighted the potent amoebicidal activity of atorvastatin without any cytotoxicity issues [7,8]. Atorvastatin belongs to the family of statins and it is a synthetic HMG-CoA (3-hidroxi-3-metilglutaril-coenzima A) reductase to the family of statins and it is a synthetic HMG-CoA (3-hidroxi-3-metilglutaril-coenzima A)
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