Novel Fe3O4 Nanoparticles with Bioactive Glass-Naproxen Coating: Synthesis, Characterization, and In Vitro Evaluation of Bioactivity.

Immune response to biomaterials, which is intimately related to their surface properties, can produce chronic inflammation and fibrosis, leading to implant failure. This study investigated the development of magnetic nanoparticles coated with silica and incorporating the anti-inflammatory drug naproxen, aimed at multifunctional biomedical applications. The synthesized nanoparticles were characterized using various techniques that confirmed the presence of magnetite and the formation of a silica-rich bioactive glass (BG) layer. In vitro studies demonstrated that the nanoparticles exhibited bioactive properties, forming an apatite surface layer when immersed in simulated body fluid, and biocompatibility with bone cells, with good viability and alkaline phosphatase activity. Naproxen, either free or encapsulated, reduced nitric oxide production, an inflammatory marker, while the BG coating alone did not show anti-inflammatory effects in this study. Overall, the magnetic nanoparticles coated with BG and naproxen showed promise for biomedical applications, especially anti-inflammatory activity in macrophages and in the bone field, due to their biocompatibility, bioactivity, and osteogenic potential.

Anti-Trypanosoma cruzi Potential of Vestitol Isolated from Lyophilized Red Propolis.

Chagas disease (CD) is a worldwide public health problem, and the drugs available for its treatment have severe limitations. Red propolis is a natural extract known for its high content of phenolic compounds and for having activity against T. cruzi. The aim of this study was to investigate the trypanocidal potential of red propolis to isolate, identify, and indicate the mode of action of the bioactive compounds. The results revealed that the total phenolic content was 15.4 mg GAE/g, and flavonoids were 7.2 mg QE/g. The extract was fractionated through liquid-liquid partitioning, and the trypanocidal potential of the samples was evaluated using the epimastigote forms of the Y strain of T. cruzi. In this process, one compound was characterized by MS, 1H, and 13C NMR and identified as vestitol. Cytotoxicity was evaluated employing MRC-5 fibroblasts and H9C2 cardiomyocytes, showing cytotoxic concentrations above 15.62 µg/mL and 31.25 µg/mL, respectively. In silico analyses were applied, and the data suggested that the substance had a membrane-permeation-enhancing effect, which was confirmed through an in vitro assay. Finally, a molecular docking analysis revealed a higher affinity of vestitol with farnesyl diphosphate synthase (FPPS). The identified isoflavan appears to be a promising lead compound for further development to treat Chagas disease.

Controlled Release and Cell Viability of Ketoconazole Incorporated in PEG 4000 Derivatives.

In recent years, polymeric materials have been gaining prominence in studies of controlled release systems to obtain improvements in drug administration. These systems present several advantages compared with conventional release systems, such as constant maintenance in the blood concentration of a given drug, greater bioavailability, reduction of adverse effects, and fewer dosages required, thus providing a higher patient compliance to treatment. Given the above, the present work aimed to synthesize polymeric matrices derived from polyethylene glycol (PEG) capable of promoting the controlled release of the drug ketoconazole in order to minimize its adverse effects. PEG 4000 is a widely used polymer due to its excellent properties such as hydrophilicity, biocompatibility, and non-toxic effects. In this work, PEG 4000 and derivatives were incorporated with ketoconazole. The morphology of polymeric films was observed by AFM and showed changes on the film organization after drug incorporation. In SEM, it was possible to notice spheres that formed in some incorporated polymers. The zeta potential of PEG 4000 and its derivatives was determined and suggested that the microparticle surfaces showed a low electrostatic charge. Regarding the controlled release, all the incorporated polymers obtained a controlled release profile at pH 7.3. The release kinetics of ketoconazole in the samples of PEG 4000 and its derivatives followed first order for PEG 4000 HYDR INCORP and Higuchi for the other samples. Cytotoxicity was determined and PEG 4000 and its derivatives were not cytotoxic.

Anti-Inflammatory, Antimicrobial, Antioxidant and Photoprotective Investigation of Red Propolis Extract as Sunscreen Formulation in Polawax Cream.

Many activities have been described for propolis, including, antiviral, antibacterial, antifungal, anti-inflammatory, immunoregulatory, antioxidant and wound healing properties. Recently, propolis has been highlighted due to its potential application in the pharmaceutical and cosmetic industries, motivating a better understanding of its antioxidant and anti-inflammatory activities. Propolis and its main polyphenolic compounds presented high antioxidant activity, and effectiveness as broad spectrum UVB and UVA photoprotection sunscreens. Through a qualitative phytochemical screening, the ethanolic red propolis extracts (EEPV) (70% at room temperature and 70% at a hot temperature) presented a positive result for flavonoids and terpenoids. It presented an antioxidant activity for reducing 50% of DPPH of 17 and 12 µg/mL for extraction at room temperature and at a hot temperature, respectively. The UPLC-QTOF-MS/MS analysis allowed the annotation of 40 substances for EEPV-Heated and 42 substances for EEPV-Room Temperature. The IC50 results of the ABTS scavenging activity was 4.7 µg/mL for both extractions, at room temperature and at a hot temperature. Additionally, we also evaluated the cytotoxic profile of propolis extracts against macrophage (RAW 264.7 cells) and keratinocytes (HaCaT cells), which showed non-cytotoxic doses in cell viability assays even after a long period of exposure. In addition, propolis extracts showed antibacterial activity for Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), demonstrating potential biological activity for the creation of formulations aimed at disease control and prevention.

Heating Capacity and Biocompatibility of Hybrid Nanoparticles for Magnetic Hyperthermia Treatment.

Cancer is one of the deadliest diseases worldwide and has been responsible for millions of deaths. However, developing a satisfactory smart multifunctional material combining different strategies to kill cancer cells poses a challenge. This work aims at filling this gap by developing a composite material for cancer treatment through hyperthermia and drug release. With this purpose, magnetic nanoparticles were coated with a polymer matrix consisting of poly (L-co-D,L lactic acid-co-trimethylene carbonate) and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer. High-resolution transmission electron microscopy and selected area electron diffraction confirmed magnetite to be the only iron oxide in the sample. Cytotoxicity and heat release assays on the hybrid nanoparticles were performed here for the first time. The heat induction results indicate that these new magnetic hybrid nanoparticles are capable of increasing the temperature by more than 5 °C, the minimal temperature rise required for being effectively used in hyperthermia treatments. The biocompatibility assays conducted under different concentrations, in the presence and in the absence of an external alternating current magnetic field, did not reveal any cytotoxicity. Therefore, the overall results indicate that the investigated hybrid nanoparticles have a great potential to be used as carrier systems for cancer treatment by hyperthermia.

Enhanced mechanical properties, anti-biofilm activity, and cytocompatibility of a methacrylate-based polymer loaded with native multiwalled carbon nanotubes.

OBJECTIVES: We aimed to optimize the mechanical and biological properties of a conventional methacrylate-based dental polymer by loading it with double- and triple-walled carbon nanotubes as growth (DTWCNTG). METHODS: A formulation of bisphenol A-glycidyl methacrylate and triethylene glycol dimethacrylate (mass ratio = 2:1) was mixed with DTWCNTG at concentrations of 0.0% (control), 0.001%, 0.005%, and 0.010%. The concentrations were physicochemical and morphologically evaluated, and antibacterial activity was assessed by seeding a Streptococcus mutans strain (ATCC 25175) on the experimental polymeric surfaces. Cellular survival and osteodifferentiation were evaluated in epithelial (HaCat) and preosteoblast cells (MC3T3-E1). RESULTS: The 0.001% DTWCNTG concentration yielded higher compressive strength, elastic modulus, flexural strength, flexural modulus, water sorption, and solubility than the control. The degree of conversion and color did not significantly change with a low amount of DTWCNTG incorporated into the polymer. Antibacterial activity significantly improved when tested on the 0.001% DTWCNTG discs. No groups showed cytotoxicity in a short-term analysis and adding DTWCNTG favored MC3T3-E1 mineralization over the control, particularly in the 0.001% formulation. SIGNIFICANCE: The micro-addition of 0.001% DTWCNTG confers mechanical resistance, antimicrobial properties, and bioactivity to methacrylate-based polymers without significantly compromising color. Incorporating DTWCNTG improved dental composite properties and could be a biomodified material for minimally invasive procedures.

Equisetum hyemale-derived unprecedented bioactive composite for hard and soft tissues engineering.

Although Bioactive Glasses (BGs) have been progressively optimized, their preparation often still involves the use of toxic reagents and high calcination temperatures to remove organic solvents. In the present work, these synthesis related drawbacks were overcome by treating the ashes from the Equisetum hyemale plant in an ethanol/water solution to develop a bioactive composite [glass/carbon (BG-Carb)]. The BG-Carb was characterized by scanning electron microscopy, and transmission electron microscopy; and its chemical composition was assessed by inductively coupled plasma-optical emission spectroscopy. Brunauer-Emmett-Teller gas adsorption analysis showed a specific surface area of 121 m2 g-1. The formation of hydroxyapatite (HA) surface layer in vitro was confirmed by Fourier-transform infrared spectroscopy analysis before and after immersion in simulated body fluid (SBF) solution. The Rietveld refinement of the XRD patterns and selected area electron diffraction analyses confirmed HA in the sample even before immersing it in SBF solution. However, stronger evidences of the presence of HA were observed after immersion in SBF solution due to the surface mineralization. The BG-Carb samples showed no cytotoxicity on MC3T3-E1 cells and osteo-differentiation capacity similar to the positive control. Altogether, the BG-Carb material data reveals a promising plant waste-based candidate for hard and soft tissue engineering.

Bioactive glass containing 90% SiO2 in hard tissue engineering: An in vitro and in vivo characterization study.

Bioactive glass has been proved to have many applications in bioengineering due to its bone regenerative properties. In this work, an innovative, highly resorbable bioactive glass containing 90% SiO2 (BG90) to be used as a bone substitute was developed. The BG90 was synthetized by the sol-gel process with the dry step at room temperature. The biomaterial showed in vitro and in vivo bioactivities even with silica content up to 90%. Moreover, the BG90 presented high porosity and surface area due to its homogenously interconnected porous network. In vitro, it was observed to have high cell viability and marked osteoblastic differentiation of rat bone marrow-derived cells when in contact with BG90 ion extracts. The BG90 transplantation into rat tibia defects was analysed at 1, 2, 3, 4, 7, and 10 weeks post-operatively and compared with the defects of negative (no graft) and positive (autogenous bone graft) controls. After 4 weeks of grafting, the BG90 was totally resorbed and induced higher bone formation than did the positive control. Bone morphogenetic protein 2 (BMP-2) expression at the grafting site peaked at 1 week and decreased similarly after 7 weeks for all groups. Only the BG90 group was still exhibiting BMP-2 expression in the last experimental time. Our data demonstrated that the BG90 could be an attractive candidate to provide useful approaches in hard-tissue bioengineering.

Current Status of Magnetite-Based Core@Shell Structures for Diagnosis and Therapy in Oncology Short running title: Biomedical Applications of Magnetite@Shell Structures.

Superparamagnetic iron oxides, as magnetite (Fe3O4) or maghemite (γ-Fe2O3), are primary materials with intrinsic properties that enable them, as single components or as special composites, to base advanced techniques in medical clinical practices, as a contrast agent in magnetic resonance imaging (MRI), as magnetically-induced hyperthermic heat generator, and as a magnetic guide to locally deliver drugs to specific sites in the human body. An interesting approach to developing nanoplatforms for those applications consists in manufacturing core@shell nanostructures, in which the precursor magnetic iron oxide (usually, magnetite) acts as a core, and an organic, or inorganic compound is used as a shell in a multifunctional composite. In this review, we report the current advances in the use of magnetite-based core@shell nanostructures, including Fe3O4@SiO2 and Fe3O4@polymers, in MRI, magnetic hyperthermia and drug delivery systems for diagnosis and therapy of tumor cells. The development of nanoplatforms for combined therapy and diagnostic (theranostic) is also addressed.

Influence of recovering collagen with bioactive glass on osteoblast behavior.

Bioactive ceramics have interesting properties from the biological standpoint, but their effects on cellular events remain partially unknown. In the current work, we investigated cellular viability, proliferation, and metabolic activity of rat primary osteoblasts in contact with four different samples: type I collagen, bioactive glass-coated collagen (GC), and both samples submitted to immersion for 5 days in a simulated body fluid. The bioactive glass coating was obtained from a sol-gel process. The cell viability, the alkaline phosphate, the collagen secretion, and the nitric oxide production by osteoblast were measured after 72 h of incubation in the presence of the samples. The GC that was immersed for 5 days in a simulated body fluid solution showed an increase in osteoblast viability and proliferation when it was compared with control and the other samples.

In vivo performance of a sol-gel glass-coated collagen.

Synthetic bioactive materials offer possibilities to repair large tissue defects. It is well known that bioactivity, angiogenesis, and inflammation are key events in implant incorporation. Using glass-coated and glass-free collagen as potential bone graft substitutes, we carried out in vitro bioactivity and an in vivo angiogenesis and inflammation studies. The in vitro study showed bioactivity when the glass-coated samples were left in SBF for 5 days. This was confirmed by FTIR results, which presented P--O vibration bands characteristic of hydroxyapatite close to 1060 cm(-1) and 600 cm(-1). The in vivo response was evaluated following subcutaneous implantation of the biomaterial in the mouse dorsa. Angiogenesis, as determined by hemoglobin content extracted from implants 7 and 14 days after implantation, increased progressively in both glass-coated and glass-free collagen implants. However, vascularization was higher in the glass-coated collagen implants 14 days after implantation (mug Hb per mg wet tissue 6.0 +/- 0.3) compared with the glass-free group (1.6 +/- 0.1). The inflammatory process, determined by the levels of myeloperoxidase and N-acetylglucosaminidase, was similar for both implants. This study shows that glass-coated collagen implants hold osteogenic and angiogenic potential and may be used in clinical conditions requiring improvement of these biological processes.

Identificaçäo de bloqueadores beta-adrenérgicos em urina por cromatografia em camada delgada para diagnóstico da intoxicaçäo / Identification of beta-adrenergic blockers in thin-layer chromatography for intoxication diagnosis

Os bloqueadores beta-adrenérgicos (BBA) säo fármacos amplamente utilizados no tratamento de algumas doenças cardiovasculares, sendo empregados, também, na ingestäo intencional de superdose, de forma isolada ou em associaçäo com outros farmacos, com a finalidade de cometer suicídio. Em nosso meio tal fato é de crescente importância. O atenolol (A), Metoprolol (M), Nadolol (N), Pindolol (Pi) e Propranolol (Pr) säo os BBA comercializados no Brasil. Com a finalidade de determinar esses BBA em material biológico, nos últimos anos, foram estabelecidas algumas metodologias analíticas. Na determinaçäo de pequenas concentraçöes (ng/m), têm sido utilizadas técnicas cromatográficas mais sofisticadas. A cromatografia em camada delgada (CCD), além de custo inferior e fácil manipulaçäo, em relaçäo a outras técnicas cromatográficas, näo necessitando de pessoal qualificado, tem sua eficiência comprovada após o uso de doses terapêuticas e subterapêuticas. O objetivo do nosso trabalho foi desenvolver uma técnica para identificaçäo dos BBA estudados, tanto para o laboratório de análises toxicológicas, quanto para laboratórios de análises clínicas, em regiöes onde näo existam laboratórios de toxicologia...