RESUMO
Drugs used for the treatment and prevention of malaria have resistance-related problems, making them ineffective for monotherapy. If properly associated, many of these antimalarial drugs may find their way back to the treatment regimen. Among the therapeutic arsenal, quinine (QN) is a second-line treatment for uncomplicated malaria but has side effects that limit its use. Curcumin (CR) is a natural compound with anti-plasmodial activities and low bioavailability. In this context, the aim of this work was to develop and characterize co-encapsulated QNâ¯+â¯CR-loaded polysorbate-coated polymeric nanocapsules (NC-QC) to evaluate their activity on Plasmodium falciparum and the safety of the nanoformulations for Caenorhabditis elegans. NC-QC displayed a diameter of approximately 200â¯nm, a negative zeta potential and a slightly basic pH. The drugs are homogeneously distributed in the NCs in the amorphous form. Co-encapsulated NCs exhibited a significant reduction in P. falciparum parasitemia, better than QN/CR. The worms exposed to NC-QC showed higher survival and longevity and no decrease in their reproductive capacity compared to free and associated drugs. It was possible to prove that the NCs were absorbed orally by the worms using fluorescence microscopy. Co-encapsulation of QN and CR was effective against P. falciparum, minimizing the toxic effects caused by chronic exposure of the free drugs in C. elegans.
Assuntos
Antimaláricos/administração & dosagem , Caenorhabditis elegans/efeitos dos fármacos , Curcumina/administração & dosagem , Nanocápsulas/administração & dosagem , Plasmodium falciparum/efeitos dos fármacos , Quinina/administração & dosagem , Animais , Antimaláricos/química , Antimaláricos/toxicidade , Linhagem Celular , Sobrevivência Celular , Curcumina/química , Curcumina/toxicidade , Eritrócitos/parasitologia , Humanos , Dose Letal Mediana , Nanocápsulas/química , Nanocápsulas/toxicidade , Poliésteres/administração & dosagem , Poliésteres/química , Poliésteres/toxicidade , Polissorbatos/administração & dosagem , Polissorbatos/química , Polissorbatos/toxicidade , Quinina/química , Quinina/toxicidade , Tensoativos/administração & dosagem , Tensoativos/química , Tensoativos/toxicidade , Triglicerídeos/administração & dosagem , Triglicerídeos/química , Triglicerídeos/toxicidadeRESUMO
Although the potential toxicity of many metallic and carbon nanoparticles to plants has been reported, few studies have evaluated the phytotoxic effects of polymeric and solid lipid nanoparticles. The present work described the preparation and characterization of chitosan/tripolyphosphate (CS/TPP) nanoparticles and solid lipid nanoparticles (SLN) and evaluated the effects of different concentrations of these nanoparticles on germination of Zea mays, Brassica rapa, and Pisum sativum. CS/TPP nanoparticles presented an average size of 233.6±12.1nm, polydispersity index (PDI) of 0.30±0.02, and zeta potential of +21.4±1.7mV. SLN showed an average size of 323.25±41.4nm, PDI of 0.23±0.103, and zeta potential of -13.25±3.2mV. Nanotracking analysis enabled determination of concentrations of 1.33×1010 (CS/TPP) and 3.64×1012 (SLN) nanoparticles per mL. At high concentrations, CS/TPP nanoparticles caused complete inhibition of germination, and thus negatively affected the initial growth of all tested species. Differently, SLN presented no phytotoxic effects. The different size and composition and the opposite charges of SLN and CS/TPP nanoparticles could be associated with the differential phytotoxicity of these nanomaterials. The present study reports the phytotoxic potential of polymeric CS/TPP nanoparticles towards plants, indicating that further investigation is needed on the effects of such formulations intended for future use in agricultural systems, in order to avoid damage to the environment.
Assuntos
Quitosana/toxicidade , Germinação/efeitos dos fármacos , Nanopartículas/toxicidade , Polifosfatos/toxicidade , Poluentes do Solo/toxicidade , Triglicerídeos/toxicidade , Brassica rapa/efeitos dos fármacos , Brassica rapa/crescimento & desenvolvimento , Química Farmacêutica , Quitosana/química , Nanopartículas/química , Tamanho da Partícula , Pisum sativum/efeitos dos fármacos , Pisum sativum/crescimento & desenvolvimento , Polímeros/química , Polímeros/toxicidade , Polifosfatos/química , Poluentes do Solo/química , Triglicerídeos/química , Zea mays/efeitos dos fármacos , Zea mays/crescimento & desenvolvimentoRESUMO
Nematicidal bioassay-guided fractionation of the n-hexane extract of the seeds of Jubaea chilensis led to the identification of eight known fatty acids and a mixture of triglycerides, reported for the first time for this species. In addition, their corresponding methyl esters were identified to be artifacts generated during the extraction and isolation procedures by using GC-EI-MS and chemical transformation methods. The fatty acid composition of the triglycerides was analyzed by GC-EI-MS and chemical transformation techniques. Among the 17 compounds, only lauric acid and myristic acid exhibited significant inhibitory effects on the movement of Caenorhabditis elegans with minimum inhibitory concentrations (MIC) of 75 microg/ml.
Assuntos
Antinematódeos/isolamento & purificação , Arecaceae/química , Ácidos Graxos/isolamento & purificação , Sementes/química , Triglicerídeos/isolamento & purificação , Animais , Antinematódeos/toxicidade , Ácidos Graxos/toxicidade , Cromatografia Gasosa-Espectrometria de Massas , Nematoides/efeitos dos fármacos , Triglicerídeos/toxicidadeRESUMO
The effects of amphotericin B associated with a triglyceride-rich emulsion (AB-emulsion), shown previously to behave like lymph chylomicrons, were evaluated in vitro and in vivo. Incorporation of amphotericin B to the emulsion was monitored by UV-visible spectrophotometry. Whilst conventional amphotericin B induced a considerable K+ efflux from erythrocytes, AB-emulsion had essentially no effect. In contrast, the K+ efflux from Candida albicans was similar upon incubation either with AB-emulsion or with conventional amphotericin B. Administration to rats showed reduced mortality due to AB-emulsion compared with conventional amphotericin B. Renal toxicity was also decreased upon AB-emulsion treatment, as evaluated by serum urea and creatinine levels. These data suggest that chylomicron-like emulsions could be utilized as vehicles for amphotericin B in antifungal therapy.