TATIANA SANTANA BALOGH

TATIANA SANTANA BALOGH

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Direct radiolabeling of PVP-nanogel from 99mTcO4
2023 - BALOGH, TATIANA S.; MARQUES, FABIO N.; KADLUBOWSKI, SLAWOMIR; LUGAO, ADEMAR B.
Nanogels are considered promising drug delivery systems for different pathologies, mainly associated with neurological disease, by intranasal administration since drug transport occurs via the olfactory nerve, causing rapid delivery to the brain. The present work aimed to evaluate a protocol for 99mTc labeling of poly(N-vinylpyrrolidone) (PVP) nanogel synthesized by an electron beam for future in vivo biodistribution assays. 10 mM PVP K-90 solution saturated with N2O was irradiated by e-beam using a dose of 7 kGy and a dose rate of 5.35 kGy/s. Nanoparticles characteristic was evaluated by DLS technique to determine the Rh and SLS to determine the Mw and Rg. Rg/Rh and ρcoil were calculated. The sample was morphologically characterized using AFM. The same analyzes were performed with a non-irradiated PVP solution. Radiolabeling was performed by mixing 0.55 mg of SnCl2.2H2O in 50 μL of HCl 0.1 M with (A) 450 μL 0.2 M NaOAc buffer, pH 4.1; (B) 200 μL 0.2 M NaOAc buffer, pH 4.1 and 0.5 M NaHCO3 buffer, pH 7.26; (C) filtered solution B in a 0.22 μm syringe filter. To the solutions (A), (B), and (C) were added 200 μL of nanogel (8.9 mg of PVP K-90), 100 μL of 99mTcO4- (860-980 μCi), and the samples were stirred at 500 rpm for 90 minutes at room temperature. The reaction was assessed by W3MM paper/acetone chromatography at the end of the process. All solutions were filtered through a 0.22 μm filter to remove 99mTcO2, as a previously validated process, and the radioactivity in the filter and the solution was measured. Finally, the solutions were concentred in the Amicon® (10 kD), and the radioactivity of the filtered and retained solution were measured too. The solution remaining on the filter was diluted with 300 μl of purified water and the concentration process was repeated twice. Filter content and the sum of filtered solutions 1 and 2 had the radioactivity measured to check labeling efficiency. Nanogel was obtained with an average for Rh of 12.49 nm, Rg of 6.8 nm, Mw of 1.32 x 106 g/mol, ρcoil of 786.98, and Rg/Rh of 0.620. High relief spherical structures were observed in the AFM images instead of the low roughness film observed in the non-irradiated PVP solution. Chromatographic analysis of the sample prepared only with NaOAc buffer (final pH 3.8) and of the sample with the mixture of buffers without previous filtration (final pH 6.8) indicated, respectively, 99.89 and 99.68% associated with the formation of 99mTc-PVP nanogel or 9mTc-colloid. In contrast, the sample prepared with the mixture of buffers and previously filtered (final pH 6.8) showed 80.10% of nonreduced 99mTcO4. Filtration results at 0.22 μm showed that the 9mTccolloid remains 100% retained in the filter, while free 99mTcO4 and 99mTc-PVP nanogel are filtered. Amicon® filtration confirmed 95.75% and 92% of 99mTc-PVP nanogel formation in the samples with NaOAc buffer and a mixture of buffers without previous filtration, respectively. It was possible to synthesize nanogel by electron beam, obtaining an average Rh of 12.49 nm. The labeling process with 99mTcO4- showed a high radiochemical yield in samples prepared with NaOAc buffer and a mixture of buffers without previous filtration.
Fabrication of green nanomaterials
2023 - THIPE, VELAPHI C.; FREITAS, LUCAS F.; LIMA, CAROLINE S.A.; BATISTA, JORGE G.S.; FERREIRA, ARYEL H.; OLIVEIRA, JUSTINE P.R. de; BALOGH, TATIANA S.; KADLUBOWSKI, SLAWOMIR; LUGAO, ADEMAR B.; KATTI, KATTESH V.
The purpose of this chapter is to discuss the production of biocompatible green nanomaterials for biomedical applications using green nanotechnology. To enhance drug loading and delivery, these nanomaterials are engineered with immunomodulatory ligands such as phytochemicals (Epigallocatechin gallate, Mangiferin, Resveratrol), proteins (albumin and papain), crosslinked hydrogels, and nanogels. The nanomaterials described herein are synthesized via redox potential of electron-dense phytochemicals that reduce metallic precursors to their stable corresponding nanoparticles and via water radiolysis with ionizing radiation as a green approach (due to the absence of any reducing agent) for use as radiosensitizers (albumin and papain nanoparticles) in nuclear medicine – theranostics applications. The phytochemicals facilitate the delivery of nanoparticles through receptor mediated endocytosis, while the proteins such as papain, due to their proteolytic action enhances the permeation of nanoparticles into tumor tissue, and albumin increase the pharmacokinetic efficiency of these nanoparticles. The nanoparticles developed have shown effectiveness against a variety of human cancers while posing no toxicity to normal tissue. Additionally, a pilot human clinical combing Ayurvedic medicine with green nanomedicine is given as a novel approach for treating breast cancer and other related illnesses. Finally, the importance of ecotoxicology for nanomaterials is discussed in order to provide safety data in relevant multiple species (fish, daphnia, algae, rodents, etc.) with paratope/epitope distributions for evaluating tissue cross-reactivity profiles in human tissues and to provide critical information on in vivo toxicity in order to predict the possible adverse effects of nanomaterials on human and environmental health as an effort to establish regulatory limits and ISO standards for nanomaterials.
Synthesis of poly(N-vinyl pyrrolidone) (PVP) nanogels by gamma irradiation using different saturation atmospheres
2022 - BALOGH, TATIANA S.; BONTURIM, EVERTON; VIEIRA, LUCAS D.; LUGAO, ADEMAR B.; KADLUBOWSKI, SLAWOMIR
Nanogels are internally crosslinked particles of nanometric size used in various fields e.g. as such as carriers in drug delivery systems. They can be produced using ionizing radiation in dilute aqueous solutions. This method is carried out in a pure polymer-solvent system, avoiding the addition of any additives such as monomers, surfactants, catalysts and crosslinking agents and no further purification step is necessary. Poly(N-vinyl pyrrolidone) (PVP K-90) nanogels were prepared by gamma irradiation in an aqueous solution. The samples were prepared in triplicate in multipurpose cobalt-60 gamma irradiator using 1, 10, 25 and 100 mM PVP solutions. Samples were irradiated in argon and nitrous oxide conditions with doses from 1 kGy up to 25 kGy with 10 kGy/h dose rate. The mean particle size (Rh) was determined by Dynamic Light Scattering (DLS) and radius of gyration (Rg) and weight-average molecular weight (Mw) by Static Light Scattering (SLS). These samples were morphologically characterized using Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM). Samples prepared with 100 mM PVP K-90 solution formed macroscopic gels, in the samples obtained with 25 mM PVP K-90 solution there was a prevalence of intermolecular crosslinking. On the other hand, in the samples generated with 10 mM PVP K-90 solution, there was a predominance of intramolecular crosslinking demonstrated in the tendency to: decrease in the radius of gyration (Rg), in the constancy of the weight-average molecular weight (Mw), in the increase in polymer coil density (ρcoil), in the Rg/Rh ratio (shape factor) around 1.0 indicating homogenous, internally cross-linked spheres, in the high relief spherical structures observed in the AFM images and in the spherical particles with high contrast observed in the TEM images. The saturation of the samples with nitrous oxide doubled formation of hydroxyl radicals, favoring the generation of polymeric radicals. Higher average number of radicals in each macromolecule contributed to the higher number of intramolecular crosslinks.
Influence of argon and nitrous oxide on the synthesis of PVP nanogels prepared by gamma radiation
2020 - BALOGH, T.S.; KADLUBOWSKI, S.; BONTURIM, E.; LUGAO, A.B.; VARCA, G.H.
Nanogels are innovative systems with great potential for use in chemotherapy, disease diagnosis, release of bioactive substances, vaccines, cell culture systems, biocatalysis, in the generation of bioactive scaffolds in regenerative medicine among other applications. The definition of this material can be directly derived from the definition of polymeric gel, that is, a two-component system consisting of a permanent three-dimensional network of linked polymer chains and solvent molecules filling the pores of this network. Its internal structure is similar to that of hydrogels however presents particle size range varying from 0 to 100 nm leading to several advantages. Nanogel production methods involve intramolecular crosslinking that can be achieved using ionizing radiation. This method avoids the addition of any additives allowing the reaction to be carried out in a pure polymer-solvent system and the production of nanogels for biomedical applications free from monomer and crosslinking agents or surfactants. In this work influence of argon and nitrous oxide on the formation of nanogels by gamma irradiation has been evaluated. The samples were prepared in duplicate in multipurpose cobalt-60 gamma irradiator using a 25 mM PVP solution. Samples were irradiated in argon and nitrous oxide conditions with doses from 1 kGy up to 25 kGy with 10 kGy/h dose rate. These samples were morphologically characterized using Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) as well as the pristine PVP solution. The mean particle size of the samples and the polydispersity index was performed in equipment Zetasizer Nano ZS - Malvern® and the determination of radius of gyration and molecular weight was performed in equipment Heleos - Wyatt®. It was observed in the conditions evaluated that saturation with argon or nitrous oxide promoted similar results except for 25 kGy dose. At this dose larger mean particle size and radius of gyration were observed in the sample saturated with nitrous oxide.
An updated review of macro, micro, and nanostructured hydrogels for biomedical and pharmaceutical applications
2020 - LIMA, CAROLINE S.A. de; BALOGH, TATIANA S.; VARCA, JUSTINE P.R.O.; VARCA, GUSTAVO H.C.; LUGAO, ADEMAR B.; CAMACHO-CRUZ, LUIS A.; BUCIO, EMILIO; KADLUBOWSKI, SLAWOMIR S.
Hydrogels are materials with wide applications in several fields, including the biomedical and pharmaceutical industries. Their properties such as the capacity of absorbing great amounts of aqueous solutions without losing shape and mechanical properties, as well as loading drugs of different nature, including hydrophobic ones and biomolecules, give an idea of their versatility and promising demand. As they have been explored in a great number of studies for years, many routes of synthesis have been developed, especially for chemical/permanent hydrogels. In the same way, stimuli-responsive hydrogels, also known as intelligent materials, have been explored too, enhancing the regulation of properties such as targeting and drug release. By controlling the particle size, hydrogel on the micro- and nanoscale have been studied likewise and have increased, even more, the possibilities for applications of the so-called XXI century materials. In this paper, we aimed to produce an overview of the recent studies concerning methods of synthesis, biomedical, and pharmaceutical applications of macro-, micro, and nanogels.