Search

Amphotericin B (AmB) is a potent polyenic antifungal agent with leishmanicidal activity. Due to its low solubility and permeability in the gastrointestinal tract, AmB is usually administered intravenously. In this context, various approaches have been used to try to improve these properties. Some of the systems developed have shown proven successful, but there is still a lack of knowledge about the pathways AmB takes after oral administration. Therefore, the aim of this work was not only to obtain aqueous dispersions containing AmB at different aggregation states, but also to entrap this molecule in nanocarriers, and evaluate the influence of these conditions on the jejunal permeability of AmB. To observe the aggregation states of AmB, physicochemical characterization of AmB-albumin complexes and AmB-loaded formulations was performed. Different degrees of AmB aggregation states were obtained. Thus, permeability tests were performed in the Ussing chamber and a decrease in AmB concentration in the donor compartment was observed. Electrophysiological measurements showed different responses depending on the AmB formulation. In conclusion, although control of the AmB aggregation state was observed by physicochemical characterization, this approach does not seem to have a sufficient effect on AmB permeability, but on its toxicity. For a complete understanding of AmB-loaded nanocarriers, other pathways, such as lymphatic absorption, should also be investigated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Liposomes have become successful nanostructured systems used in clinical practices. These vesicles are able to carry important drug loadings with noteworthy stability. The aim of this work was to develop iron oxide-loaded stealth liposomes as a prospective alternative for the treatment of lung cancer. In this study, citric acid iron oxide nanoparticles (IONPs-Ac) were synthesized and encapsulated in stealth liposomes. Their cytotoxicity and selectivity against lung tumor cells were assessed. Stealth liposomal vesicles, with relevant content of IONPs-Ac, named ferri-liposomes (SL-IONPs-Ac), were produced with an average size of 200 nm. They displayed important cytotoxicity in a human lung cancer cells model (A549 cells), even at low concentrations, whereas free IONPs-Ac displayed adequate biocompatibility. Nevertheless, the treatment at the same concentration of ferri-liposomes against HEK-293 cells, a normal human cell lineage, was not significantly cytotoxic, revealing a probable lung tumor selectiveness of the fabricated formulation. Furthermore, from the flow cytometry studies, it was possible to infer that ferri-liposomes were able to induce A549 tumor cells death through apoptosis/ferroptosis processes, evidenced by a significant reduction of the mitochondrial membrane potential.

Scorpion envenomation has been considered a public health issue around the world. Tityus serrulatus represents a specie of major medical importance in Brazil due to mortality rates of approximately 1% among children and elderly populations. The aim of this work was to evaluate the in vivo anti-inflammatory potential of aqueous extract from Hancornia speciosa fruits, its fractions and its phenolic compounds against T. serrulatus envenomation. After receiving the T. serrulatus venom (TsV, 0.8 mg/kg) intraperitoneally, the animals were treated intravenously with the aqueous extract (20, 30 and 40 mg/kg), the arachnid antivenom (50 μL/animal), the dichloromethane, ethyl acetate and n-butanol fractions (20 mg/kg) as well as rutin and chlorogenic acid (2, 2.5 and 5 mg/kg). The treatment with the aqueous extract, fractions and phenolic compounds decreased the migration of leukocytes to the peritoneal cavity and reduced the levels of IL-1β, IL-6 and IL-12. Moreover, the pulmonary histopathologic analysis showed a reduction in both interstitial and alveolar edema, as well as in the leukocytes infiltration and vascular ectasia in the mice's lungs, which evidences a protective effect attributed to H. speciosa. This is the first study that demonstrates the inhibitory potential of the aqueous extract from H. speciosa fruits against inflammation induced by TsV. These findings suggest that the bioactive compounds from the aqueous extract, especially chlorogenic acid and rutin, are responsible for the reported anti-inflammatory activity of H. speciosa., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Chloroquine diphosphate (CQ) is a hydrophilic drug with low entrapment efficiency in hydrophobic nanoparticles (NP). Herpes simplex virus type 1 (HSV-1) is an enveloped double-stranded DNA virus worldwide known as a common human pathogen. This study aims to develop chloroquine-loaded poly(lactic acid) (PLA) nanoparticles (CQ-NP) to improve the chloroquine anti- HSV-1 efficacy. CQ-NP were successfully prepared using a modified emulsification-solvent evaporation method. Physicochemical properties of the NP were monitored using dynamic light scattering, atomic force microscopy, drug loading efficiency, and drug release studies. Spherical nanoparticles were produced with modal diameter of <300 nm, zeta potential of -20 mv and encapsulation efficiency of 64.1%. In vitro assays of CQ-NP performed in Vero E6 cells, using the MTT-assay, revealed different cytotoxicity levels. Blank nanoparticles (B-NP) were biocompatible. Finally, the antiviral activity tested by the plaque reduction assay revealed greater efficacy for CQ-NP compared to CQ at concentrations equal to or lower than 20 µg mL -1 ( p < 0.001). On the other hand, the B-NP had no antiviral activity. The CQ-NP has shown feasible properties and great potential to improve the antiviral activity of drugs.

Amphotericin B (AmB) is effective against visceral leishmaniasis (VL), but the renal toxicity of the conventional form, mixed micelles with deoxycholate (M-AmB), is often dose-limiting, while the less toxic lipid-based formulations such as AmBisome ® are very expensive. Two different strategies to improve the therapeutic index of AmB with inexpensive ingredients were evaluated on this work: (i) the heat treatment of the commercial formulation (H-AmB) and (ii) the preparation of an AmB-loaded microemulsion (ME-AmB). M-AmB was heated to 70 °C for 20 min. The resulting product was characterized by UV spectrophotometry and circular dichroism, showing super-aggregates formation. ME-AmB was prepared from phosphate buffer pH 7.4, Tween 80 ® , Lipoid S100 ® and Mygliol 812 ® with AmB at 5 mg/mL. The droplet size, measured by dynamic light scattering, was about 40 nm and transmission electron microscopy confirmed a spherical shape. Rheological analysis showed low viscosity and Newtonian behavior. All the formulations were active in vitro and in vivo against Leishmania donovani (LV9). A selectivity index (CC 50 on RAW/IC 50 on LV9) higher than 10 was observed for ME-AmB, H-AmB and AmBisome ® . Furthermore, no important in vivo toxicity was observed for all the samples. The in-vivo efficacy of the formulations after IV administration was evaluated in Balb/C mice infected with LV9 (three doses of 1 mg/kg AmB) and no significant difference was observed between H-AmB, M-AmB, ME-AmB and AmBisome ® . In conclusion, these two inexpensive alternative formulations for AmB showing good efficacy and selectivity for Leishmania donovani merit further investigation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Microemulsions (MEs) loaded with methyl dihydrojasmonate (MJ) were developed to improve the aqueous solubility of this drug. The composition of the formulations ranged according to the oil/surfactant ratio (O/S). The MEs were characterized according to diameter of droplets, X-ray diffraction and polarized light microscopy. The MJ identification and quantification was performed by gas chromatography-mass spectrometry (GC-MS). The MJ showed a retention time of ∼16.7 min for all samples. The obtained correlation coefficient from the calibration graph was 0.991. The developed analytical method was effective enough to quantify low and high concentrations of MJ. The increase of the O/S ME ratio led to a reduction of the droplet diameter. All formulations showed an amorphous structure and the behavior varied between isotropic and anisotropic systems. A decrease in the release of MJ with the increase of the O/S ratio in the formulations was observed. The analytical method developed for the quantitative determination of MJ is suitable to detect and quantify the drug compound from different compositions of MEs in the in vitro release test, and by analogy in other prolonged effects related to the drug reservoir effect of these systems was observed, revealing that ME can be a promising nanocarrier for MJ delivery to tumor cells.

In this study, biodegradable and biocompatible gamma irradiated poly-(dl-lactide-co-glycolide) (PLGA) spray-dried microparticles were prepared aiming to improve the efficacy of methotrexate (MTX). The experimental design included three formulations of microparticles containing distinct drug amount (9%, 18%, and 27% w/w) and three distinct gamma irradiation dose (15kGy, 25kGy, and 30kGy). The physicochemical and drug release properties of the microparticles supported their biocompatibility and biological efficacy studies in different cell lines. The irradiation induced slight changes in the spherical shape of the microparticles and the formation of free radicals was dependent on the drug loading. However, the amorphous character, particle size, drug loading, and drug release rate of the microparticles were preserved. The drug release data from all microparticles formulation were evaluated by using four drug kinetic models and by comparison of their similarity factor (f 2 ). The gamma irradiation did not induce changes in the biocompatibility of PLGA microparticles and in the biological activity of the MTX-loaded microparticles. Finally, the spray-dried MTX-loaded PLGA microparticles enhanced the efficacy of the drug in the human cervical cancer cells (SiHa cell line). This study demonstrated the feasibility of the gamma irradiated spray dried PLGA microparticles for prolonged release of MTX, supporting a promising antitumor-drug delivery system for parenteral (subcutaneous) or pulmonary use., (Copyright © 2017 Elsevier B.V. All rights reserved.)