Lipid reducing potential of liposomes loaded with ethanolic extract of purple pitanga (Eugenia uniflora) administered to Caenorhabditis elegans.

The ethanolic extract obtained from purple pitanga fruit (Eugenia uniflora - PPE) has been previously described by its potential to reduce lipid accumulation in vitro. In this study, we aimed to study this potential in vivo using Caenorhabditis elegans as animal model. Considering the low pH of the extract, its hydrophilic characteristic, its absorption by the medium where the worms are cultivated and the need of a chronic exposure in the worms solid medium, we have loaded liposomes with PPE and investigated its potential for oral administration. Following 48 h exposure to the PPE-loaded liposomes on worms nematode growth medium, we did not observe any toxic effects of the formulation. Under high cholesterol diet, which increased worms total lipid and also triacylglycerides levels, liposomes containing PPE were able to significantly attenuate these alterations, which could not be observed when worms were treated with free PPE. Furthermore, we could evidence that liposomes were ingested by worms through their labelling to uranin fluorescence dye. Through total phenolic compounds quantification, we estimated an entrapment efficacy of PPE into liposomes of 87.7%. The high levels of phenolic compounds present in PPE, as previously described by our group, indicate that these antioxidants may interfere in worms lipid metabolism, which may occur through many and intricated mechanisms. Although the use of conventional liposomes for human consumption may not be pragmatic, its application for oral delivery of a hydrophilic substance in C. elegans was absolutely critical for our experimental design and has proven to be efficient.

Optimization of Curcuma Oil/Quinine-Loaded Nanocapsules for Malaria Treatment.

Quinine, a treatment used in chloroquine-resistant falciparum malaria, was loaded into poly(ɛ-caprolactone) or Eudragit® RS100 nanocapsules using Curcuma oil as the oil-based core. Until now, the effect of cationic nanocapsules on malaria has not been reported. A 24 factorial design was adopted using, as independent variables, the concentration of Curcuma oil, presence of quinine, type of polymer, and aqueous surfactant. Diameter, zeta potential, and pH were the responses studied. The formulations were also evaluated for drug content, encapsulation efficiency, photostability, and antimalarial activity against Plasmodium berghei-infected mice. The type of polymer influenced all of the responses studied. Quinine-loaded Eudragit® RS100 (F13) and PCL nanocapsules (F9), both with polysorbate 80 coating, showed nanometric particle size, positive zeta potential, neutral pH, high drug content, and quinine photoprotection ability; thus, these nanocapsules were selected for in vivo tests. Both formulations showed lower levels of parasitemia from the beginning of the experiment (5.78 ± 3.60 and 4.76 ± 3.46% for F9 and F13, respectively) and highest survival mean time (15.3 ± 2.0 and 14.9 ± 5.6 days for F9 and F13, respectively). F9 and F13 showed significant survival curve compared to saline, thus demonstrating that nanoencapsulation improved bioefficacy of QN and co-encapsulated curcuminoids, regardless of the surface charge.

The use of Brazilian vegetable oils in nanoemulsions: an update on preparation and biological applications

ABSTRACT Vegetable oils present important pharmacological properties, which gained ground in the pharmaceutical field. Its encapsulation in nanoemulsions is considered a promising strategy to facilitate the applicability of these natural compounds and to potentiate the actions. These formulations offer several advantages for topical and systemic delivery of cosmetic and pharmaceutical agents including controlled droplet size, protection of the vegetable oil to photo, thermal and volatilization instability and ability to dissolve and stabilize lipophilic drugs. For these reasons, the aim of this review is to report on some characteristics, preparation methods, applications and especially analyze recent research available in the literature concerning the use of vegetable oils with therapeutic characteristics as lipid core in nanoemulsions, specially from Brazilian flora, such as babassu (Orbignya oleifera), aroeira (Schinus molle L.), andiroba (Carapa guaianiensis), casca-de-anta (Drimys brasiliensis Miers), sucupira (Pterodon emarginatus Vogel) and carqueja doce (Stenachaenium megapotamicum) oils.

Clozapine-Loaded Polysorbate-Coated Polymeric Nanocapsules: Physico-Chemical Characterization and Toxicity Evaluation in Caenorhabditis elegans Model.

The aim of this work was to develop and characterize clozapine loaded polysorbate-coated polymeric nanocapsules and assess their toxicity in Caenorhabditis elegans, an invertebrate animal model. Formulations were prepared by nanoprecipitation method and characterized by particle size, zeta potential, pH, drug loading, entrapment efficiency and in vitro drug release. All nanocapsules prepared presented diameter around 140 nm, pH slightly acid and negative zeta potential. In vitro studies showed biphasic drug release from nanocapsules with decreasing of the release rate on nanoencapsulation. The t(1/2)beta of clozapine was 7.23 +/- 0.73 and 2.23 +/- 0.97 h for nanoencapsulated and free drug, respectively (p < 0.05), in pH 1.2 medium. Similar results were obtained in pH 6.8 buffer. Regarding toxicity evaluation, worms exposed to clozapine-loaded nanocapsules did not show the same mortality rate compared to others formulations, as the survival was significantly higher than the free drug treated-group. In addition, we observed that free clozapine decreased egg laying at the first reproductive day, whereas nanoencapsulated clozapine did not depict significant change of this parameter. Longevity assay showed no significant difference, demonstrating that the toxicological effects of clozapine observed in C. elegans are acute. In addition, we proved that free and nanoencapsulated clozapine were orally uptake by the worms, as determined by fluorescein-labeled nanocapsules. Then, the use of nanocapsules delayed the drug release and minimized the toxic effects of clozapine in worms, which can be used as a new animal model to evaluate the nanotoxicity of drug delivery systems.