Pyrimethamine-loaded lipid-core nanocapsules to improve drug efficacy for the treatment of toxoplasmosis

Abstract

We propose an innovative product based on the nanoencapsulation of pyrimethamine (PYR), aiming an improvement of drug efficacy for the treatment of toxoplasmosis. The in vitro cytotoxicity effect of encapsulated PYR and PYR-colloidal suspension was concomitantly evaluated against LLC-MK2 lineage and mouse peritoneal macrophage showing that the cells had similar tolerance for both PYR encapsulated or in the aqueous suspension. CF1 mice acutely infected with tachyzoites of Toxoplasma gondii RH strain treated with different doses (5.0-10 mg/kg/day) of PYR-nanocapsules had survival rate higher than the animals treated with the same doses of non-encapsulated PYR. Thus, encapsulation of PYR improved the efficacy of this drug against an acute model of toxoplasmosis in mice and can be considered an alternative for reducing the dose of PYR, which, in turn, could also reduce the side effects associated to the treatment.

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

“…[2][3][4][5] Lipid-core nanocapsules (LNC) are a special type of particle due to the hybrid characteristics between polymeric and lipid NP. 6 These particles have an organogel core formed by a mixture of sorbitan monostearate and medium chain triglycerides, which increases drug encapsulation capacity by up to 40 times. 7 Recently, it has been described that the polymeric nanocapsules, prepared with poly(ε-caprolactone) (PCL) and polysorbate 80 (PS80), may improve the biological action 4,8 of drugs, increase the drug bioavailability, 9 and in case of antioxidant substances, their encapsulation has been shown to be able to improve their Dovepress Dovepress 5094 charão et al antioxidant properties.…”

“…Recently, other studies have also shown the promise of nanocarriers with LNC for the oral administration of drugs. 6,15 For instance, Frozza et al 15 showed a higher accumulation of resveratrol in brain tissue after oral administration of resveratrol-loaded LNC compared to the oral administration of the drug in a hydroalcoholic solution. Likewise, Pissinate et al 6 observed an increase in survival of animals infected with Toxoplasma gondii after oral treatment with pyrimethamine-loaded LNC.…”

“…6,15 For instance, Frozza et al 15 showed a higher accumulation of resveratrol in brain tissue after oral administration of resveratrol-loaded LNC compared to the oral administration of the drug in a hydroalcoholic solution. Likewise, Pissinate et al 6 observed an increase in survival of animals infected with Toxoplasma gondii after oral treatment with pyrimethamine-loaded LNC. This result was attributed to a probable increase in the central nervous system concentration of pyrimethamine promoted by the LNC, in this important site of infection by T. gondii.…”

“…This result was attributed to a probable increase in the central nervous system concentration of pyrimethamine promoted by the LNC, in this important site of infection by T. gondii. 6 The uptake and distribution assessment of these nanocapsules presents an interesting challenge. Hirsjärvi et al studied lipid nanocapsules and lipid nanoemulsions in different models, in vitro uptake and distribution in mice, as well as cancer treatment.…”

Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model

“…25,[29][30][31] The formulations used in this study, MTX-LNC and LNC, exhibited unimodal particle-size distribution profiles by laser diffraction with nanoscopic z-average diameter and PDIs ,0.2, which demonstrate narrow nanoscopic particle-size distributions and a D90 ,309±10 (NTA). The physicochemical parameters indicate that the formulation is adequate for intravenous administration.…”