RESUMO
The dioctadecyldimethylammonium bromide (DODAB) is a double-chained cationic lipid with potent bactericide and fungistatic activities; however, its toxicity on protozoan parasites is still unknown. Here, we show the antileishmanial activity of DODAB nano-sized cationic bilayer fragments on stationary-phase promastigotes and amastigotes of Leishmania amazonensis, the causative agent of cutaneous leishmaniasis. Upon treatment with DODAB, we analyzed the parasite surface zeta-potential, parasite viability, cellular structural modifications, and intracellular proliferation. The DODAB cytotoxic effect was dose-dependent, with a median effective concentration (EC50) of 25 µM for both life-cycle stages, comparable to the reported data for bacteria and fungi. The treatment with DODAB changed the membrane zeta-potential from negative to positive, compromised the parasite's morphology, affected the cell size regulation, caused a loss of intracellular organelles, and probably dysregulated the plasma membrane permeability without membrane disruption. Moreover, the parasites that survived after treatment induced small parasitophorous vacuoles and failed to proliferate inside macrophages. In conclusion, DODAB displayed antileishmanial activity, and it remains to be elucidated how DODAB acts on the protozoan membrane. Understanding this mechanism can provide insights into the development of new parasite-control strategies.
Assuntos
Antiprotozoários/química , Antiprotozoários/farmacologia , Cátions/química , Leishmania mexicana/efeitos dos fármacos , Nanopartículas/química , Compostos de Amônio Quaternário/química , Animais , Leishmaniose Cutânea/tratamento farmacológico , Estágios do Ciclo de Vida/efeitos dos fármacos , Lipídeos/química , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Nanostructured particles of polystyrene sulfate (PSS) covered by a cationic lipid bilayer of dioctadecyldimethylammonium bromide (DODAB) incorporated gramicidin D (Gr) yielding optimal and broadened bactericidal activity against both Escherichia coli and Staphylococcus aureus. The adsorption of DODAB/Gr bilayer onto PSS nanoparticles (NPs) increased the zeta-average diameter by 8-10 nm, changed the zeta-potential of the NPs from negative to positive, and yielded a narrow size distributions for the PSS/DODAB/Gr NPs, which displayed broad and maximal microbicidal activity at very small concentrations of the antimicrobials, namely, 0.057 and 0.0057 mM DODAB and Gr, respectively. The results emphasized the advantages of highly-organized, nanostructured, and cationic particles to achieve hybrid combinations of antimicrobials with broad spectrum activity at considerably reduced DODAB and Gr concentrations.
RESUMO
The optimization of bilayer coverage on particles is important for a variety of biomedical applications, such as drug, vaccine, and genetic material delivery. This work aims at optimizing the deposition of cationic bilayers on silica over a range of experimental conditions for the intervening medium and two different assemblies for the cationic lipid, namely, lipid films or pre-formed lipid bilayer fragments. The lipid adsorption on silica in situ over a range of added lipid concentrations was determined from elemental analysis of carbon, hydrogen, and nitrogen and related to the colloidal stability, sizing, zeta potential, and polydispersity of the silica/lipid nanoparticles. Superior bilayer deposition took place from lipid films, whereas adsorption from pre-formed bilayer fragments yielded limiting adsorption below the levels expected for bilayer adsorption.