DSpace Collection:
https://hdl.handle.net/10171/52056
2024-03-29T00:41:56ZComparison of antibacterial activity and cytotoxicity of silver nanoparticles and silver-loaded montmorillonite and saponite
https://hdl.handle.net/10171/67908
Title: Comparison of antibacterial activity and cytotoxicity of silver nanoparticles and silver-loaded montmorillonite and saponite
Abstract: Although silver nanoparticles are known for their antibacterial activity, little research has been carried out on
what synthesis method provides the most effective particles. In this study, silver nanoparticles were synthesised
via chemical reduction by using silver nitrate as the silver precursor, ascorbic acid as the reducing agent and
sodium citrate as the stabilising agent. The solutions were adjusted to several pH values employing sodium
hydroxide, citric acid or nitric acid. Dynamic light scattering and absorption spectra in the ultraviolet/visible
region characterisation revealed that employing nitric acid to adjust the pH produced more varied and larger
silver particle sizes. Then, silver nanoparticles were supported on montmorillonite and saponite through wet
impregnation or ion exchange methods. Scanning electron microscopy, energy-dispersive X-ray spectroscopy and
transmission electron microscopy characterisation confirmed that silver nanoparticles were successfully loaded
onto the clay minerals. Next, the antibacterial activity of the samples was evaluated against Escherichia coli and
Staphylococcus aureus by determining their minimum inhibitory concentrations and minimum bactericidal concentrations. The free silver nanoparticles did not show any antibacterial activity at 125 mg/L. In contrast, the
silver-loaded samples obtained by wet impregnation and with a higher silver content displayed the strongest
antibacterial effect. Finally, the cytotoxicity of the samples was determined in GM07492-A cell line by using an
XTT colorimetric assay. The calculated IC50 values revealed that the supported silver nanoparticles were barely
toxic. Thus, the silver-loaded clay minerals obtained here are promising antibacterial materials with a high-grade
safety profile.2023-01-01T00:00:00ZMixed micelles and gels of a hydrophilic poloxamine (Tetronic 1307) and miltefosine: Structural characterization by small-angle neutron scattering and in vitro evaluation for the treatment of leishmaniasis
https://hdl.handle.net/10171/67907
Title: Mixed micelles and gels of a hydrophilic poloxamine (Tetronic 1307) and miltefosine: Structural characterization by small-angle neutron scattering and in vitro evaluation for the treatment of leishmaniasis
Abstract: Hypothesis/background: Tetronic is a family of four-armed amphiphilic block copolymers of polyethylene
oxide (PEO) and polypropylene oxide (PPO) that self-aggregate to form micelles and hydrogels. Due to
their temperature and pH-responsiveness, they are emerging as smart nanomaterials in the area of drug
delivery. Here we propose the use of Tetronic 1307 (T1307) as a nanocarrier of miltefosine (MF), a zwitterionic alkylphospholipid highly active against leishmaniasis, one of the most threating neglected tropical diseases. Given the amphiphilic nature of the drug, both surfactants can combine to form mixed
micelles, reducing the cytotoxicity of MF by lowering its dose and improving its internalization, hence
its antileishmanial effect.
Experiments: The structure of the T1307 micelles, MF micelles, mixed micelles and hydrogels, formed in
buffered solution (pH = 7.4) at different concentrations has been investigated in-depth by a combination
of small-angle neutron scattering (SANS), dynamic light scattering (DLS), fluorescence spectroscopy and
nuclear magnetic resonance methods (1D, 2D NOESY, and diffusion NMR). The cytotoxicity of the aggregates in macrophages has been assessed, as well as the antileishmanial activity in both Leishmania major
promastigotes and amastigotes.
Findings: T1307 and MF combine into mixed aggregates over a wide range of temperatures and compositions, forming ellipsoidal core–shell mixed micelles. The shell is highly hydrated and comprises most
of the PEO blocks, while the hydrophobic core contains the PO blocks and the MF along with a fraction of
EO and water molecules, depending on the molar ratio in the mixture. The combination with T1307
amplified the leishmanicidal activity of the drug against both forms of the parasite and dramatically
reduced drug cytotoxicity. T1307 micelles also showed a considerable leishmanicidal activity without
exhibiting macrophage toxicity. These results support the use of T1307 as a MF carrier for the treatment
of human and animal leishmaniasis, in its different clinical forms.2023-01-01T00:00:00ZProtective passive immunity in escherichia coli ETEC-challenged neonatal mice conferred by orally immunized dams with nanoparticles containing homologous outer membrane vesicles
https://hdl.handle.net/10171/67782
Title: Protective passive immunity in escherichia coli ETEC-challenged neonatal mice conferred by orally immunized dams with nanoparticles containing homologous outer membrane vesicles
Abstract: Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in
mammals, including neonatal, recently weaned pigs and infant human beings. We have previously
shown that outer membrane vesicles (OMV) obtained from ETEC serotypes encapsulated into zein
nanoparticles, coated with a Gantrez-mannosamine polymer conjugate (OMV-NP), were immunogenic
in mice and sows. In the present study, we show that pups from vaccinated mice were protected
against ETEC F4 serotype challenge through maternal passive immunization. OMV from F4 cultures
were collected and characterized. Two-week-pregnant BALB/c mice were orally immunized with
a single dose of vesicles (0.2 mg) either free (OMV) or encapsulated into nanoparticles (OMV-NP).
Evaluation of the antibodies in serum (IgG1, Ig2a or IgA) and feces (IgA) of dams immunized with
OMV-NP revealed an enhancement of specific immunogenicity. The antibody response conferred
by the nanoparticle adjuvant was also correlated with IL-6 and IL-10 splenic levels. Each mother
was allowed to feed her progeny for one week. Suckling pups presented specific IgA in feces
demonstrating their passive immunization through colostrum intake. Two weeks after the pups were
born, they were infected orally with a single dose of F4 E. coli (1.2 × 108 CFU/pup). Results showed
that 70% of the pups from dams immunized with OMV-NP were protected. In contrast, 80% of
the pups from dams immunized with free OMV died as a result of the experimental challenge.
These findings support the use of zein nanoparticles coated with a Gantrez-mannosamine shield as
adjuvant delivery system for the oral immunization during pregnancy to confer immunity to the
offspring through maternal immunization2020-01-01T00:00:00ZNext generation of selenocyanate and diselenides with upgraded leishmanicidal activity
https://hdl.handle.net/10171/67681
Title: Next generation of selenocyanate and diselenides with upgraded leishmanicidal activity
Abstract: Nowadays, leishmaniasis is still treated with outdated drugs that present several obstacles related to their high toxicity, long duration, parenteral administration, high costs and drug resistance. Therefore, there is an urgent demand for safer and more effective novel drugs. Previous studies indicated that selenium compounds are promising derivatives for innovative therapy in leishmaniasis treatment. With this background, a new library of 20 selenocyanate and diselenide derivatives were designed based on structural features present in the leishmanicidal drug miltefosine. Compounds were initially screened against promastigotes of L. major and L. infantum and their cytotoxicity was evaluated in THP-1 cells. Compounds B8 and B9 were the most potent and less cytotoxic and were further screened for the intracellular back transformation assay. The results obtained revealed that B8 and B9 showed EC50 values of 7.7 µM and 5.7 µM, respectively, in L. major amastigotes, while they presented values of 6.0 µM and 7.4 µM, respectively, against L. infantum amastigotes. Furthermore, they exerted high selectivity (60 < SI > 70) towards bone marrow-derived macrophages. Finally, these compounds exhibited higher TryR inhibitory activity than mepacrine (IC50 7.6 and 9.2 µM, respectively), and induced nitric oxide (NO) and reactive oxygen species (ROS) production in macrophages. These results suggest that the compounds B8 and B9 could not only exert a direct leishmanicidal activity against the parasite but also present an indirect action by activating the microbicidal arsenal of the macrophage. Overall, these new generation of diselenides could constitute promising leishmanicidal drug candidates for further studies.2023-01-01T00:00:00Z