Publications by authors named "Patrícia Severino"

142 Publications

Annatto Oil Loaded Nanostructured Lipid Carriers: A Potential New Treatment for Cutaneous Leishmaniasis.

Pharmaceutics 2021 Nov 11;13(11). Epub 2021 Nov 11.

Laboratory of Drug Development, Department of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil.

Annatto ( L.) is extensively used as food pigment worldwide. Recently, several studies have found it to have healing and antioxidant properties, as well as effective action against leishmaniasis. Therefore, the purpose of this study was to incorporate the oil obtained from annatto seeds into a nanostructured lipid carrier (NLC) and evaluate its physicochemical properties and biological activity against . Nanoparticles were prepared by the fusion-emulsification and ultrasonication method, with the components Synperonic™ PE (PL) as the surfactant, cetyl palmitate (CP) or myristyl myristate (MM) as solid lipids, annatto oil (AO) (2% and 4%, /) as liquid lipid and active ingredient, and ultra-pure water. Physicochemical and biological characterizations were carried out to describe the NLCs, including particle size, polydispersity index (PDI), and zeta potential (ZP) by dynamic light scattering (DLS), encapsulation efficiency (EE%), thermal behavior, X-ray diffraction (XRD), transmission electron microscopy (TEM), Electron Paramagnetic Resonance (EPR), cytotoxicity on BALB/c 3T3 fibroblasts and immortalized human keratinocyte cells, and anti-leishmaniasis activity in vitro. Nanoparticles presented an average diameter of ~200 nm (confirmed by TEM results), a PDI of less than 0.30, ZP between -12.6 and -31.2 mV, and more than 50% of AO encapsulated in NLCs. Thermal analyses demonstrated that the systems were stable at high temperatures with a decrease in crystalline structure due to the presence of AOs (confirmed by XRD). In vitro, the anti-leishmania test displayed good activity in encapsulating AO against . The results indicate that the oily fraction of L. in NLC systems should be evaluated as a potential therapeutic agent against leishmaniasis.
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http://dx.doi.org/10.3390/pharmaceutics13111912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618414PMC
November 2021

Effects of electrically conductive nano-biomaterials on regulating cardiomyocyte behavior for cardiac repair and regeneration.

Acta Biomater 2021 Nov 21. Epub 2021 Nov 21.

Division of Engineering in Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Cambridge, MA 02139, USA. Electronic address:

Myocardial infarction (MI) represents one of the most prevalent cardiovascular diseases, with a highly relevant and impactful role in public health. Despite the therapeutic advances of the last decades, MI still begets extensive death rates around the world. The pathophysiology of the disease correlates with cardiomyocyte necrosis, caused by an imbalance in the demand of oxygen to cardiac tissues, resulting from obstruction of the coronary flow. To alleviate the severe effects of MI, the use of various biomaterials exhibit vast potential in cardiac repair and regeneration, acting as native extracellular matrices. These hydrogels have been combined with nano sized or functional materials which possess unique electrical, mechanical, and topographical properties that play important roles in regulating phenotypes and the contractile function of cardiomyocytes even in adverse microenvironments. These nano-biomaterials' differential properties have led to substantial healing on in vivo cardiac injury models by promoting fibrotic scar reduction, hemodynamic function preservation, and benign cardiac remodeling. In this review, we discuss the interplay of the unique physical properties of electrically conductive nano-biomaterials, are able to manipulate the phenotypes and the electrophysiological behavior of cardiomyocytes in vitro, and can enhance heart regeneration in vivo. Consequently, the understanding of the decisive roles of the nano-biomaterials discussed in this review could be useful for designing novel nano-biomaterials in future research for cardiac tissue engineering and regeneration. STATEMENT OF SIGNIFICANCE: This study introduced and deciphered the understanding of the role of multimodal cues in recent advances of electrically conductive nano-biomaterials on cardiac tissue engineering. Compared with other review papers, which mainly describe these studies based on various types of electrically conductive nano-biomaterials, in this review paper we mainly discussed the interplay of the unique physical properties (electrical conductivity, mechanical properties, and topography) of electrically conductive nano-biomaterials, which would allow them to manipulate phenotypes and the electrophysiological behaviour of cardiomyocytes in vitro and to enhance heart regeneration in vivo. Consequently, understanding the decisive roles of the nano-biomaterials discussed in the review could help design novel nano-biomaterials in future research for cardiac tissue engineering and regeneration.
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http://dx.doi.org/10.1016/j.actbio.2021.11.022DOI Listing
November 2021

Genotoxicity Assessment of Metal-Based Nanocomposites Applied in Drug Delivery.

Materials (Basel) 2021 Nov 1;14(21). Epub 2021 Nov 1.

Polo das Ciências da Saúde, Departament of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.

Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for several applications in the biomedical field, from therapeutics to diagnostics. Green nanocomposites stand for nanoparticles of biocompatible, biodegradable and non-toxic profiles. When using metal nanoparticles for drug delivery, the question of how hazardous these "virus-sized particles" can be is posed, due to their nanometer size range with enhanced reactivity compared to their respective bulk counterparts. These structures exhibit a high risk of being internalized by cells and interacting with the genetic material, with the possibility of inducing DNA damage. The Comet Assay, or Single-Cell Gel Electrophoresis (SCGE), stands out for its capacity to detect DNA strand breaks in eukaryotic cells. It has huge potential in the genotoxicity assessment of nanoparticles and respective cells' interactions. In this review, the Comet assay is described, discussing several examples of its application in the genotoxicity evaluation of nanoparticles commonly administered in a set of routes (oral, skin, inhaled, ocular and parenteral administration). In the nanoparticles boom era, where guidelines for their evaluation are still very limited, it is urgent to ensure their safety, alongside their quality and efficacy. Comet assay or SCGE can be considered an essential tool and a reliable source to achieve a better nanotoxicology assessment of metal nanoparticles used in drug delivery.
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http://dx.doi.org/10.3390/ma14216551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585152PMC
November 2021

Liposomal formulations of oxybutynin and resiniferatoxin for the treatment of urinary diseases: improvement of drug tolerance upon intravesical.

Drug Deliv Transl Res 2021 Oct 20. Epub 2021 Oct 20.

CEB - Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.

The use of liposomes for drug release has demonstrated to be a promising therapeutic platform for biomedical applications. In this study, intravesical administration of OXI (1.5 mM) and RTX (100 nM) was used to compare histological changes caused in Wistar female rats by the drugs both unloaded and loaded in liposomes. After instillation of formulations by intravesical catheter, bladders were removed and histological analysis carried out at pre-determined time intervals over a period of 60 days. Urinalysis was performed to verify the presence of infection and of liposomes. Results showed that RTX caused a higher bladder damage, with inflammatory reaction that reached all bladder layers. After 60 days, RTX-treated group showed urothelial alterations, collagen replacement by fibrosis and also abdominal adherence, but not the OXI-treated group. At the end of the assay, the liposomal-treated groups showed a minimal inflammatory reaction and significantly increased bladder size. Moreover, urinalysis confirmed the presence of liposomes in rat urine. RTX promoted higher bladder damage than OXI. Intravesical administration of liposomal OXI or RTX formulations minimized inflammatory reaction, with an extended drug effect on bladders. After a single intravesical administration, liposomes were found in rat urine samples after 60 days.
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http://dx.doi.org/10.1007/s13346-021-01082-6DOI Listing
October 2021

Bacillus thuringiensis: From biopesticides to anticancer agents.

Biochimie 2021 Oct 12. Epub 2021 Oct 12.

Industrial Biotechnology Program, University of Tiradentes (UNIT), Av. Murilo Dantas, Aracaju, Brazil. Electronic address:

Bacillus thuringiensis (Bt) is a ubiquitous bacterium that produces several proteins that are toxic to different invertebrates such as insects, nematodes, mites, and also some protozoans. Among these, Cry and Cyt proteins are most explored as biopesticides for their action against agricultural pests and vectors of human diseases. In 2000, a group of researchers from Japan isolated parasporal inclusion proteins from B. thuringiensis, and reported their cytotoxic action against human leukemia. Later, other proteins with similar antitumor properties were also isolated from this bacterium and these cytotoxic proteins with specific activity against human cancer cells were named parasporins. At present, nineteen different parasporins are registered and classified in six families. These parasporins have been described to have specific in vitro antitumor activity against several cancer cell lines. The antitumor activity makes parasporins possible candidates as anticancer agents. Various research groups around the world are involved in isolating and characterizing in vitro antitumor activity of these proteins and many articles reporting such activities in detail have been published. However, there are virtually no data regarding the antitumor activity of parasporins in vivo. This review summarizes the properties of these potentially useful antitumor agents of natural origin, focusing on their in vivo activity thus also highlighting the importance of testing these proteins in animal models for a possible application in clinical oncology.
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http://dx.doi.org/10.1016/j.biochi.2021.10.003DOI Listing
October 2021

Extracellular vesicles cargo from head and neck cancer cell lines disrupt dendritic cells function and match plasma microRNAs.

Sci Rep 2021 09 17;11(1):18534. Epub 2021 Sep 17.

Centro de Pesquisa Experimental, Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.

Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients' plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.
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http://dx.doi.org/10.1038/s41598-021-97753-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448882PMC
September 2021

Hyaluronic acid-coated chitosan nanoparticles as carrier for the enzyme/prodrug complex based on horseradish peroxidase/indole-3-acetic acid: Characterization and potential therapeutic for bladder cancer cells.

Enzyme Microb Technol 2021 Oct 2;150:109889. Epub 2021 Aug 2.

Tiradentes University, Av. Murilo Dantas 300, 49032-490, Aracaju, SE, Brazil; Institute of Technology and Research, Av. Murilo Dantas 300, 49032-490, Aracaju, SE, Brazil. Electronic address:

Hybrid nanoparticles composed of different biopolymers for delivery of enzyme/prodrug systems are of interest for cancer therapy. Hyaluronic acid-coated chitosan nanoparticles (CS/HA NP) were prepared to encapsulate individually an enzyme/pro-drug complex based on horseradish peroxidase (HRP) and indole-3-acetic acid (IAA). CS/HA NP showed size around 158 nm and increase to 170 and 200 nm after IAA and HRP encapsulation, respectively. Nanoparticles showed positive zeta potential values (between +20.36 mV and +24.40 mV) and higher encapsulation efficiencies for both nanoparticles (up to 90 %) were obtained. Electron microscopy indicated the formation of spherical particles with smooth surface characteristic. Physicochemical and thermal characterizations suggest the encapsulation of HRP and IAA. Kinetic parameters for encapsulated HRP were similar to those of the free enzyme. IAA-CS/HA NP showed a bimodal release profile of IAA with a high initial release (72 %) followed by a slow-release pattern. The combination of HRP-CS/HA NP and IAA- CS/HA NP reduced by 88 % the cell viability of human bladder carcinoma cell line (T24) in the concentrations 0.5 mM of pro-drug and 1.2 μg/mL of the enzyme after 24 h.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109889DOI Listing
October 2021

Lipid-Polymeric Films: Composition, Production and Applications in Wound Healing and Skin Repair.

Pharmaceutics 2021 Aug 4;13(8). Epub 2021 Aug 4.

Laboratory of Drug Development, Department of Pharmacy, School of Pharmacy, Federal University of Rio Grande do Norte, Natal 59078-970, Brazil.

The use of lipids in the composition of polymeric-based films for topical administration of bioactive ingredients is a recent research topic; while few products are commercially available, films containing lipids represent a strategic area for the development of new products. Some lipids are usually used in polymeric-based film formulations due to their plasticizing action, with a view to improving the mechanical properties of these films. On the other hand, many lipids have healing, antimicrobial, anti-inflammatory, anti-aging properties, among others, that make them even more interesting for application in the medical-pharmaceutical field. This manuscript discusses the production methods of these films both on a laboratory and at industrial scales, the properties of the developed biopolymers, and their advantages for the development of dermatologic and cosmetic products.
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http://dx.doi.org/10.3390/pharmaceutics13081199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398446PMC
August 2021

Encapsulation of Active Pharmaceutical Ingredients in Lipid Micro/Nanoparticles for Oral Administration by Spray-Cooling.

Pharmaceutics 2021 Jul 31;13(8). Epub 2021 Jul 31.

Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.

Nanoencapsulation via spray cooling (also known as spray chilling and spray congealing) has been used with the aim to improve the functionality, solubility, and protection of drugs; as well as to reduce hygroscopicity; to modify taste and odor to enable oral administration; and many times to achieve a controlled release profile. It is a relatively simple technology, it does not require the use of low-cost solvents (mostly associated to toxicological risk), and it can be applied for lipid raw materials as excipients of oral pharmaceutical formulations. The objective of this work was to revise and discuss the advances of spray cooling technology, with a greater emphasis on the development of lipid micro/nanoparticles to the load of active pharmaceutical ingredients for oral administration.
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http://dx.doi.org/10.3390/pharmaceutics13081186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399666PMC
July 2021

Micro- and Nano-Based Transdermal Delivery Systems of Photosensitizing Drugs for the Treatment of Cutaneous Malignancies.

Pharmaceuticals (Basel) 2021 Aug 6;14(8). Epub 2021 Aug 6.

Massachusetts College of Pharmacy and Health Sciences, University, Boston, MA 02115, USA.

Photodynamic therapy is one of the more unique cancer treatment options available in today's arsenal against this devastating disease. It has historically been explored in cutaneous lesions due to the possibility of focal/specific effects and minimization of adverse events. Advances in drug delivery have mostly been based on biomaterials, such as liposomal and hybrid lipoidal vesicles, nanoemulsions, microneedling, and laser-assisted photosensitizer delivery systems. This review summarizes the most promising approaches to enhancing the photosensitizers' transdermal delivery efficacy for the photodynamic treatment for cutaneous pre-cancerous lesions and skin cancers. Additionally, discussions on strategies and advantages in these approaches, as well as summarized challenges, perspectives, and translational potential for future applications, will be discussed.
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http://dx.doi.org/10.3390/ph14080772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401127PMC
August 2021

Rutin-Functionalized Multi-Walled Carbon Nanotubes: Molecular Docking, Physicochemistry and Cytotoxicity in Fibroblasts.

Toxics 2021 Jul 22;9(8). Epub 2021 Jul 22.

Institute of Technology and Research (ITP), University of Tiradentes (UNIT), Av. Murilo Dantas, 300, Aracaju 49010-390, Brazil.

Multi-Walled Carbon Nanotubes (MWCNT) have been functionalized with rutin through three steps (i. reaction step; ii. purification step; iii. drying step) and their physicochemical properties investigated with respect to morphological structure, thermal analysis, Fourier Transform Infrared Spectroscopy (FTIR), and cytotoxicity. The molecular docking suggested the rutin-functionalized MWCNT occurred by hydrogen bonds, which was confirmed by FTIR assays, corroborating the results obtained by thermal analyses. A tubular shape, arranged in a three-dimensional structure, could be observed. Mild cytotoxicity observed in 3T3 fibroblasts suggested a dose-effect relationship after exposure. These findings suggest the formation of aggregates of filamentous structures on the cells favoring the cell penetration.
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http://dx.doi.org/10.3390/toxics9080173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402452PMC
July 2021

Biosurfactants: Properties and Applications in Drug Delivery, Biotechnology and Ecotoxicology.

Bioengineering (Basel) 2021 Aug 13;8(8). Epub 2021 Aug 13.

CEB-Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal.

Surfactants are amphiphilic compounds having hydrophilic and hydrophobic moieties in their structure. They can be of synthetic or of microbial origin, obtained respectively from chemical synthesis or from microorganisms' activity. A new generation of ecofriendly surfactant molecules or biobased surfactants is increasingly growing, attributed to their versatility of applications. Surfactants can be used as drug delivery systems for a range of molecules given their capacity to create micelles which can promote the encapsulation of bioactives of pharmaceutical interest; besides, these assemblies can also show antimicrobial properties. The advantages of biosurfactants include their high biodegradability profile, low risk of toxicity, production from renewable sources, functionality under extreme pH and temperature conditions, and long-term physicochemical stability. The application potential of these types of polymers is related to their properties enabling them to be processed by emulsification, separation, solubilization, surface (interfacial) tension, and adsorption for the production of a range of drug delivery systems. Biosurfactants have been employed as a drug delivery system to improve the bioavailability of a good number of drugs that exhibit low aqueous solubility. The great potential of these molecules is related to their auto assembly and emulsification capacity. Biosurfactants produced from bacteria are of particular interest due to their antibacterial, antifungal, and antiviral properties with therapeutic and biomedical potential. In this review, we discuss recent advances and perspectives of biosurfactants with antimicrobial properties and how they can be used as structures to develop semisolid hydrogels for drug delivery, in environmental bioremediation, in biotechnology for the reduction of production costs and also their ecotoxicological impact as pesticide alternative.
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http://dx.doi.org/10.3390/bioengineering8080115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389267PMC
August 2021

Exploring Innovative Leishmaniasis Treatment: Drug Targets from Pre-Clinical to Clinical Findings.

Chem Biodivers 2021 Sep 9;18(9):e2100336. Epub 2021 Aug 9.

Post-Graduation Program in Industrial Biotechnology, University of Tiradentes, Aracaju, Sergipe, Brazil.

Leishmaniasis is a group of tropical diseases caused by parasitic protozoa belonging to the genus Leishmania. The disease is categorized in cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). The conventional treatment is complex and can present high toxicity and therapeutic failures. Thus, there is a continuing need to develop new treatments. In this review, we focus on the novel molecules described in the literature with potential leishmanicidal activity, categorizing them in pre-clinical (in vitro, in vivo), drug repurposing and clinical research.
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http://dx.doi.org/10.1002/cbdv.202100336DOI Listing
September 2021

Biosynthesis of Silver Nanoparticles Mediated by Entomopathogenic Fungi: Antimicrobial Resistance, Nanopesticides, and Toxicity.

Antibiotics (Basel) 2021 Jul 13;10(7). Epub 2021 Jul 13.

University of Tiradentes (Unit), Av. Murilo Dantas, Aracaju 49010-390, Brazil.

Silver nanoparticles are widely used in the biomedical and agri-food fields due to their versatility. The use of biological methods for the synthesis of silver nanoparticles has increased considerably due to their feasibility and high biocompatibility. In general, microorganisms have been widely explored for the production of silver nanoparticles for several applications. The objective of this work was to evaluate the use of entomopathogenic fungi for the biological synthesis of silver nanoparticles, in comparison to the use of other filamentous fungi, and the possibility of using these nanoparticles as antimicrobial agents and for the control of insect pests. In addition, the in vitro methods commonly used to assess the toxicity of these materials are discussed. Several species of filamentous fungi are known to have the ability to form silver nanoparticles, but few studies have been conducted on the potential of entomopathogenic fungi to produce these materials. The investigation of the toxicity of silver nanoparticles is usually carried out in vitro through cytotoxicity/genotoxicity analyses, using well-established methodologies, such as MTT and comet assays, respectively. The use of silver nanoparticles obtained through entomopathogenic fungi against insects is mainly focused on mosquitoes that transmit diseases to humans, with satisfactory results regarding mortality estimates. Entomopathogenic fungi can be employed in the synthesis of silver nanoparticles for potential use in insect control, but there is a need to expand studies on toxicity so to enable their use also in insect control in agriculture.
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http://dx.doi.org/10.3390/antibiotics10070852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300670PMC
July 2021

Nanotherapeutics and nanotheragnostics for cancers: properties, pharmacokinetics, biopharmaceutics, and biosafety.

Curr Pharm Des 2021 Aug 3. Epub 2021 Aug 3.

Faculty of Pharmacy, University of Coimbra, Polo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra. Portugal.

With the worldwide increasing rate of chronic diseases, such as cancer, the development of novel techniques to improve the efficacy of therapeutic agents is highly demanded. Nanoparticles are especially well suited to encapsulate drugs and other therapeutic agents, bringing additional advantages, such as less frequent dosage requirements, reduced side effects due to specific targeting, and therefore increased patient compliance. However, with the increasing use of nanoparticles and their recent launch on the pharmaceutical market it is important to achieve high quality control of these advanced systems. In this review, we discuss the properties of different nanoparticles, the pharmacokinetics, the biosafety issues of concern, and conclude with novel nanotherapeutics and nanotheragnostics for cancer drug delivery.
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http://dx.doi.org/10.2174/1381612827666210804102645DOI Listing
August 2021

Analysis of the mechanisms of action of isopentenyl caffeate against Leishmania.

Biochimie 2021 Oct 1;189:158-167. Epub 2021 Jul 1.

University of Tiradentes (Unit), Biotechnological Postgraduate Program, Aracaju, Sergipe, Brazil; Institute of Technology and Research (ITP), Nanomedicine and Nanotechnology Laboratory (LNMed), Aracaju, Sergipe, Brazil.

Leishmaniasis is a neglected parasitic disease for which the conventional treatment can be considered inefficient and extremely aggressive, generating several and severe side effects. Therefore, the discovery of new drug candidates is important for the improvement in the quality of life of patients. Previously, we reported the promising results of isopentyl caffeate (ICaf) against Leishmania chagasi (agent of visceral leishmaniasis) and Leishmania amazonensis (agent of cutaneous leishmaniasis) promastigotes, displaying IC of 1.56 and 1.71 μM, respectively. Herein, we aimed to decipher the mechanisms of anti-Leishmania action of ICaf. Light and scanning electron microscopy assays showed relevant morphological changes in promastigotes when treated with ICaf, including rounding of the parasite body, shortening of the flagellum, blebs on the plasma membrane and cellular aggregation. The parasite mitochondrion was targeted by ICaf, resulting in a significant reduction in its metabolic activity and electric membrane potential followed by an increase in the production of reactive oxygen species, which culminated in the loss of plasma membrane integrity and parasite death. Relevantly, ICaf also had a potent anti-amastigote action. The IC values calculated for intracellular amastigotes of L. amazonensis were 3.27, 1.60 and 1.52 μM, while for L. chagasi the values were 2.48, 1.84 and 1.60 μM, respectively, after treating the infected macrophages with ICaf for 24, 48 and 72 h. ICaf was well tolerated by THP-1 macrophages, which gave rise to excellent selectivity indexes considering both Leishmania species. The current results suggest that ICaf may emerge as a chemotherapeutic alternative for the treatment of leishmaniasis.
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http://dx.doi.org/10.1016/j.biochi.2021.06.015DOI Listing
October 2021

Histological Evidence of Wound Healing Improvement in Rats Treated with Oral Administration of Hydroalcoholic Extract of .

Curr Issues Mol Biol 2021 Jun 11;43(1):335-352. Epub 2021 Jun 11.

Post-Graduating Program in Health and Environment, Tiradentes University, Av. Murilo Dantas, 300, Aracaju Sergipe 49010-390, Brazil.

Plant extracts rich in phenolic compounds have been demonstrated to accelerate wound healing, but their use by oral route has been poorly studied. The leaves of are rich in phenolic acids and flavonoids. The goal of this study was to assess the healing properties of the oral administration of hydroalcoholic extract of leaves (HEVL) in a murine model. HEVL was obtained by Soxhlet and dynamic maceration, and their yield and phenolic acids and flavonoid contents were determined. For the wound healing assay, 8 mm wounds were performed on the back of 48 Wistar rats, assigned into four groups ( = 12): CTR (distilled water), HEVL100, HEVL200, and HEVL300 (HEVL at 100, 200, and 300 mg/kg, respectively). On days 7 and 14, wound closure rates were assessed, and the healing wounds were subjected to histological analysis. Soxhlet-obtained extract was selected for the wound healing assay because it provided a higher yield and phenolic acid and flavonoid contents. HEVL significantly reduced leukocytosis in the peripheral blood ( < 0.05), accelerated wound closure ( < 0.05), and improved collagenization ( < 0.05) on day 7, as well as enhanced the epidermal tissue thickness ( < 0.001) and elastic fiber deposition on day 14 ( < 0.01). Furthermore, HEVL promoted an increase in the histological grading of wound healing on both days 7 and 14 ( < 0.01). The doses of 200 and 300 mg/kg provided better results than 100 mg/Kg. Our data provide histological evidence that the oral administration of HEVL improves wound healing in rodents. Therefore, the extract can be a potential oral medicine for healing purposes.
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http://dx.doi.org/10.3390/cimb43010028DOI Listing
June 2021

Nanopesticides in Agriculture: Benefits and Challenge in Agricultural Productivity, Toxicological Risks to Human Health and Environment.

Toxics 2021 Jun 4;9(6). Epub 2021 Jun 4.

Laboratory of Biomaterials and Nanotechnology-LaBNUS, University of Sorocaba, Sorocaba 18078-005, Brazil.

Nanopesticides are nanostructures with two to three dimensions between 1 to 200 nm, used to carry agrochemical ingredients (AcI). Because of their unique properties, the loading of AcI into nanoparticles offers benefits when compared to free pesticides. However, with the fast development of new engineered nanoparticles for pests' control, a new type of environmental waste is being produced. This paper describes the nanopesticides sources, the harmful environmental and health effects arising from pesticide exposure. The potential ameliorative impact of nanoparticles on agricultural productivity and ecosystem challenges are extensively discussed. Strategies for controlled release and stimuli-responsive systems for slow, sustained, and targeted AcI and genetic material delivery are reported. Special attention to different nanoparticles source, the environmental behavior of nanopesticides in the crop setting, and the most recent advancements and nanopesticides representative research from experimental results are revised. This review also addresses some issues and concerns in developing, formulating and toxicity pesticide products for environmentally friendly and sustainable agriculture.
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http://dx.doi.org/10.3390/toxics9060131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230079PMC
June 2021

Homeobox gene amplification and methylation in oral squamous cell carcinoma.

Arch Oral Biol 2021 Sep 8;129:105195. Epub 2021 Jun 8.

Department of Oral Pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil. Electronic address:

Objectives: Investigate the DNA copy number and the methylation profile of the homeobox genes HOXA5, HOXA7, HOXA9, HOXB5, HOXB13, HOXC12, HOXC13, HOXD10, HOXD11, IRX4 and ZHX1, and correlate them with clinicopathological parameters and overall survival.

Material And Methods: DNA from OSCC samples and surgical margins were submitted to DNA amplification by qPCR and to DNA methylation analysis using a DNA Methylation PCR Array System.

Results: HOXA5, HOXB5 and HOXD10 were amplified in surgical margins while HOXA9, HOXB13 and IRX4 were amplified in OSCC. HOXD10 demonstrated hypermethylation in half of the tumor while ZHX1 did not show hypermethylation. No correlation of DNA copy number or methylation with clinicopathological parameters or survival was observed.

Conclusion: HOXA9, HOXB13 and IRX4 genes appears to be regulated by amplification and HOXD10 by methylation in OSCC. Further studies are needed to determine the role of these events in OSCC development.
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http://dx.doi.org/10.1016/j.archoralbio.2021.105195DOI Listing
September 2021

Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration.

Pharmaceutics 2021 May 10;13(5). Epub 2021 May 10.

Laboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, Brazil.

The therapeutic use of peptides has increasingly recognized in the development of new therapies. However, the susceptible enzymatic cleavage is a barrier that needs to overcome. Nose-to-brain delivery associated with liposomes can protect peptides against biodegradation and improve the accessibility to brain targets. The aim was to develop a liposomal formulation as ghrelin carrier. The quality by design (QbD) approach was used as a strategy for method development. The initial risk assessments were carried out using a fishbone diagram. A screening design study was performed for the critical material attributes/critical process parameters (CMAs/CPPs) on critical quality attributes (CQAs). Liposomes were obtained by hydrating phospholipid films, followed by extrusion or homogenization, and coated with chitosan. The optimized liposome formulation was produced by high-pressure homogenization coated with chitosan, and the resulted were liposomes size 72.25 ± 1.46 nm, PDI of 0.300 ± 0.027, the zeta potential of 50.3 ± 1.46 mV, and encapsulation efficiency of 53.2%. Moreover, chitosan coating improved performance in ex vivo permeation and mucoadhesion analyzes when compared to the uncoated liposome. In this context, chitosan coating is essential for the performance of the formulations in the ex vivo permeation and mucoadhesion analyzes. The intranasal administration of ghrelin liposomes coated with chitosan offers an innovative opportunity to treat cachexia.
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http://dx.doi.org/10.3390/pharmaceutics13050686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151022PMC
May 2021

Psoriasis: From Pathogenesis to Pharmacological and Nano-Technological-Based Therapeutics.

Int J Mol Sci 2021 May 7;22(9). Epub 2021 May 7.

Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain.

Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The understanding of age-related factors, gender, and genetic predisposition of these multifactorial diseases has been instrumental for the development of new pharmacological and technological treatment approaches. In this review, we discuss the molecular mechanisms behind the pathological features of psoriasis, also addressing the currently available treatments and novel therapies that are under clinical trials. Innovative therapies developed over the last 10 years have been researched. In this area, advantages of nanotechnological approaches to provide an effective drug concentration in the disease site are highlighted, together with microneedles as innovative candidates for drug delivery systems in psoriasis and other inflammatory chronic skin diseases.
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http://dx.doi.org/10.3390/ijms22094983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125586PMC
May 2021

Essential Oil Attenuates Bleomycin-Induced Pulmonary Fibrosis in a Murine Model.

Pharmaceutics 2021 May 9;13(5). Epub 2021 May 9.

Post-Graduating Program in Biotechnology, Brazilian Biotechnology Northeast Network, Tiradentes University, Aracaju 49010-390, Brazil.

The essential oil of (EOCW) is a natural product with antioxidant, anti-inflammatory, and antifibrotic properties. We studied the effect of EOCW in the progression of histological changes of pulmonary fibrosis (PF) in a rodent model. The oil was obtained by hydrodistillation and characterized using gas chromatography-mass spectrometry. Intratracheal instillation of bleomycin was performed in 30 rats to induce PF, while Sham animals were subjected to instillation of saline solution. The treatment was performed using daily oral administration of distilled water, EOCW at 50, 100, and 200 mg/kg, and deflazacort (DFC). After 28 days, hemogram and bronchoalveolar lavage fluid (BALF), tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were assayed. Histological grading of PF, immunohistochemical expression of α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) were also analyzed. The EOCW major compounds were found to be citronellal, geraniol, and citronellol. EOCW significantly reduced inflammation in BALF, reduced MDA levels, and increased SOD activity. EOCW attenuated histological grading of PF and reduced immunohistochemical expression of α-SMA and TGF-β in a dose-dependent way, likely due to the reduction of oxidative stress, inflammation, and TGF-β-induced myofibroblast differentiation.
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http://dx.doi.org/10.3390/pharmaceutics13050679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150729PMC
May 2021

Chitosan and chitosan/PEG nanoparticles loaded with indole-3-carbinol: Characterization, computational study and potential effect on human bladder cancer cells.

Mater Sci Eng C Mater Biol Appl 2021 May 31;124:112089. Epub 2021 Mar 31.

Tiradentes University - UNIT, Av. Murilo Dantas 300, 49032-490 Aracaju, SE, Brazil; Institute of Technology and Research - ITP, Av. Murilo Dantas 300, 49032-490 Aracaju, SE, Brazil. Electronic address:

Indole-3-carbinol (I3C) is a plant molecule known to be active against several types of cancer, but some chemical characteristics limit its clinical applications. In order to overcome these limitations, polymeric nanoparticles can be used as carrier systems for targeted delivery of I3C. In this study, chitosan and chitosan/polyethylene glycol nanoparticles (CS NP and CS/PEG NP, respectively) were prepared to encapsulate I3C by ionic gelation method. The polymeric nanoparticles were characterized by Dynamic Scattering Light (DLS), Zeta Potential (ZP), Fourier Transform Infrared (FTIR) spetroscopy, X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Field Emission Gun Scanning Electron Microscopy (FEG-SEM). I3C release testing was performed at an acidic media and the interactions between I3C and chitosan or PEG were evaluated by Density Functional Theory (DFT). Cytotoxicity of nanoparticles in bladder cancer T24 cell line was evaluated by the Methyl-thiazolyl-tetrazolium (MTT) colorimetric assay. The average size of the nanoparticles was observed to be in the range from 133.3 ± 3.7 nm to 180.4 ± 2.7 nm with a relatively homogeneous distribution. Samples had relatively high positive zeta potential values (between +20.3 ± 0.5 mV and + 24.3 ± 0.5 mV). Similar encapsulation efficiencies (about 80%) for both nanoparticles were obtained. Physicochemical and thermal characterizations pointed to the encapsulation of I3c. electron microscopy showed spherical particles with smooth or ragged surface characteristics, depending on the presence of PEG. The mathematical fitting of the release profile demonstrated that I3C-CS NP followed the Higuchi model whereas I3C-CS/PEG NP the Korsmeyer-Peppas model. Chemical differences between the nanoparticles as based on the I3C/CS or I3C/PEG interactions were demonstrate by computational characterization. The assessment of cell viability by the MTT test showed that the presence of both free I3C and I3C-loaded nanoparticles lead to statistically significant reduction in T24 cells viability in the concentrations from 500 to 2000 μM, when comparison to the control group after 24 h of exposure. Thus, CS and CS/PEG nanoparticles present as feasible I3C carrier systems for cancer therapy.
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http://dx.doi.org/10.1016/j.msec.2021.112089DOI Listing
May 2021

Cancer Nanopharmaceuticals: Physicochemical Characterization and In Vitro/In Vivo Applications.

Cancers (Basel) 2021 Apr 15;13(8). Epub 2021 Apr 15.

Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland.

Physicochemical, pharmacokinetic, and biopharmaceutical characterization tools play a key role in the assessment of nanopharmaceuticals' potential imaging analysis and for site-specific delivery of anti-cancers to neoplastic cells/tissues. If diagnostic tools and therapeutic approaches are combined in one single nanoparticle, a new platform called nanotheragnostics is generated. Several analytical technologies allow us to characterize nanopharmaceuticals and nanoparticles and their properties so that they can be properly used in cancer therapy. This paper describes the role of multifunctional nanoparticles in cancer diagnosis and treatment, describing how nanotheragnostics can be useful in modern chemotherapy, and finally, the challenges associated with the commercialization of nanoparticles for cancer therapy.
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http://dx.doi.org/10.3390/cancers13081896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071188PMC
April 2021

Effect of Chitosan and Aloe Vera Extract Concentrations on the Physicochemical Properties of Chitosan Biofilms.

Polymers (Basel) 2021 Apr 7;13(8). Epub 2021 Apr 7.

Department of Chemical Engineering, Institute of Environmental, Chemical and Pharmaceutical Sciences (ICAQF), Federal University of São Paulo (UNIFESP), Diadema, São Paulo 09913-030, Brazil.

Chitosan films have been extensively studied as dressings in formulations for the treatment of chronic wounds. The incorporation of aloe vera ( Miller) into chitosan dressings could potentialize the healing process since aloe vera shows several pharmacological activities. This work aimed to evaluate the effect of aloe vera and chitosan concentrations on the physicochemical properties of the developed films. The films were obtained by casting technique and characterized with respect to their color parameters, morphology, barrier and mechanical properties, and thermal analysis. Results showed that the presence of aloe vera modified the films' color parameters, changed barrier properties, increased fluid handling capacity (FHC), and decreased water-vapor permeability (WVP). The reduced elongation at break resulted in more rigid films. Aloe vera concentration did not significantly change film properties, but the presence of this gel increased the films' stability at temperatures below 200 °C, showing similar behavior as chitosan films above 400 °C. The results suggest a crosslinking/complexation between chitosan and aloe vera, which combine appropriate physicochemical properties for application as wound dressing materials.
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http://dx.doi.org/10.3390/polym13081187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067903PMC
April 2021

Are Nanobiosensors an Improved Solution for Diagnosis of ?

Pharmaceutics 2021 Apr 3;13(4). Epub 2021 Apr 3.

Postgraduate Program in Industrial Biotechnology, Universidade Tiradentes, Aracaju 49032-490, Brazil.

Leishmaniasis is one of the deadliest neglected tropical diseases affecting 12-15 million people worldwide, especially in middle- and low-income countries. Rapid and accurate diagnosis of the disease is important for its adequate management and treatment. Several techniques are available for the diagnosis of leishmaniasis. Among these, parasitological and immunological tests are most widely used. However, in most cases, the utilized diagnostic techniques are not good enough, showing cross-reactivity and reduced accuracy. In recent years, many new methods have been reported with potential for improved diagnosis. This review focuses on the diagnosis of exploring the biosensors and nanotechnology-based options for their detection. New developments including the use of nanomaterials as fluorophores, fluorescence quenchers as reducing agents and as dendrimers for signal improvement and amplification, together with the use of aptamers to replace antibodies are described. Future research opportunities to overcome the current limitations on the available diagnostic approaches are also discussed.
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http://dx.doi.org/10.3390/pharmaceutics13040491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066167PMC
April 2021

Using genetic variants to evaluate the causal effect of cholesterol lowering on head and neck cancer risk: A Mendelian randomization study.

PLoS Genet 2021 04 22;17(4):e1009525. Epub 2021 Apr 22.

MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.

Head and neck squamous cell carcinoma (HNSCC), which includes cancers of the oral cavity and oropharynx, is a cause of substantial global morbidity and mortality. Strategies to reduce disease burden include discovery of novel therapies and repurposing of existing drugs. Statins are commonly prescribed for lowering circulating cholesterol by inhibiting HMG-CoA reductase (HMGCR). Results from some observational studies suggest that statin use may reduce HNSCC risk. We appraised the relationship of genetically-proxied cholesterol-lowering drug targets and other circulating lipid traits with oral (OC) and oropharyngeal (OPC) cancer risk using two-sample Mendelian randomization (MR). For the primary analysis, germline genetic variants in HMGCR, NPC1L1, CETP, PCSK9 and LDLR were used to proxy the effect of low-density lipoprotein cholesterol (LDL-C) lowering therapies. In secondary analyses, variants were used to proxy circulating levels of other lipid traits in a genome-wide association study (GWAS) meta-analysis of 188,578 individuals. Both primary and secondary analyses aimed to estimate the downstream causal effect of cholesterol lowering therapies on OC and OPC risk. The second sample for MR was taken from a GWAS of 6,034 OC and OPC cases and 6,585 controls (GAME-ON). Analyses were replicated in UK Biobank, using 839 OC and OPC cases and 372,016 controls and the results of the GAME-ON and UK Biobank analyses combined in a fixed-effects meta-analysis. We found limited evidence of a causal effect of genetically-proxied LDL-C lowering using HMGCR, NPC1L1, CETP or other circulating lipid traits on either OC or OPC risk. Genetically-proxied PCSK9 inhibition equivalent to a 1 mmol/L (38.7 mg/dL) reduction in LDL-C was associated with an increased risk of OC and OPC combined (OR 1.8 95%CI 1.2, 2.8, p = 9.31 x10-05), with good concordance between GAME-ON and UK Biobank (I2 = 22%). Effects for PCSK9 appeared stronger in relation to OPC (OR 2.6 95%CI 1.4, 4.9) than OC (OR 1.4 95%CI 0.8, 2.4). LDLR variants, resulting in genetically-proxied reduction in LDL-C equivalent to a 1 mmol/L (38.7 mg/dL), reduced the risk of OC and OPC combined (OR 0.7, 95%CI 0.5, 1.0, p = 0.006). A series of pleiotropy-robust and outlier detection methods showed that pleiotropy did not bias our findings. We found limited evidence for a role of cholesterol-lowering in OC and OPC risk, suggesting previous observational results may have been confounded. There was some evidence that genetically-proxied inhibition of PCSK9 increased risk, while lipid-lowering variants in LDLR, reduced risk of combined OC and OPC. This result suggests that the mechanisms of action of PCSK9 on OC and OPC risk may be independent of its cholesterol lowering effects; however, this was not supported uniformly across all sensitivity analyses and further replication of this finding is required.
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http://dx.doi.org/10.1371/journal.pgen.1009525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096036PMC
April 2021

Oxidative stability of high oleic sunflower oil during deep-frying process of purple potato .

Heliyon 2021 Mar 8;7(3):e06294. Epub 2021 Mar 8.

Department of Pharmacy, University of Napoli Federico II, Via. D. Montesano 49, 80131, Napoli, Italy.

The behaviour of high oleic sunflower oil in deep frying process of purple potato has been evaluated simulating a fast food cooking process. This oil was used for 8h/day for 6 days, filling up from the 2nd day. A discontinuous and prolonged procedure was tested. Free Fatty Acidity (FFA), Peroxide Value (PV), Total Polar Compounds (TPC), Fatty Acid (FA) composition, Volatile Organic Compounds (VOC) have been determined at different times in thermo-oxidized (T-OX) oil, and in frying oil. The FFA in T-OX oil samples showed values in the range 0.09%-0.24%, whereas in the frying oil values varied in a range between 0.09% and 0.16%. TPCs values varied from 1.76% to 38.24% in T-OX oils, whereas in frying oil used for frying purple potatoes (FOPP) showed values in the range from 1.76 to 29.13%. The peroxides values did not follow a regular pattern, both during thermo-oxidation and during frying. Among the Long Chain Fatty Acids (LCFAs), oleic acid was the most represented (84.13%). Short chain fatty acids (SCFAs) amount was 0.34% (octanoic acid). Medium chain fatty acids (MCFA) amount was 4.45% (palmitic acid). During the thermo-oxidation, the poly-unsaturated fatty acids (PUFA) amount decreased during the 48 h of heat treatment, reaching an amount of 6.21%. This determined the increase in short chain fatty acids (SCFA). Trans fatty acids increased with the frying time. Unsaturated fatty acids (UFA) reached the value of 90.19%; SFA was 9.79%, and octanoic acid was 0.20%. A correlation between TPC vs UFA/SFA and TPC vs C18:2/C16:0 was observed in the frying oil. The most abundant volatile compounds in frying oil (from 0 to 48 h) were the aldehydes produced by decomposition of hydroperoxides of oleic and linoleic acids.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035487PMC
March 2021

Prevalence of , and -Carrying Plasmids in Isolated in a Brazilian Hospital.

Pathogens 2021 Mar 12;10(3). Epub 2021 Mar 12.

Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo 05652-900, Brazil.

carbapenemase (KPC) actively hydrolyzes carbapenems, antibiotics often used a last-line treatment for multidrug-resistant bacteria. KPC clinical relevance resides in its widespread dissemination. In this work, we report the genomic context of KPC coding genes , and in multidrug-resistant isolates from Brazil. Plasmids harboring and were identified. Fifteen additional carbapenem-resistant isolates were selected from the same tertiary hospital, collected over a period of 8 years. Their genomes were sequenced in order to evaluate the prevalence and dissemination of -harboring plasmids. We found that genes were mostly carried by one of two isoforms of transposon Tn (Tna or Tnb) that were predominantly located on plasmids highly similar to the previously described plasmid pKPC_FCF3SP (IncN). The identified pKPC_FCF3SP-like plasmids carried either or . Two isolates harbored pKpQIL-like (IncFII) plasmids, only recently identified in Brazil; one of them harbored in a Tna transposon. Underlining the risk of horizontal spread of KPC coding genes, this study reports the prevalence of and the recent spread of and , in association with different isoforms of Tn, together with high synteny of plasmid backbones among isolates studied here and in comparison with previous reports.
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http://dx.doi.org/10.3390/pathogens10030332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998191PMC
March 2021

Silver nanoparticles obtained from Brazilian pepper extracts with synergistic anti-microbial effect: production, characterization, hydrogel formulation, cell viability, and efficacy.

Pharm Dev Technol 2021 Jun 16;26(5):539-548. Epub 2021 Mar 16.

Laboratory of Nanotechnology and Nanomedicine (LNMED), Institute of Technology and Research (ITP), Tiradentes University (UNIT), Aracaju, Brazil.

The synthesis of silver nanoparticles using plant extracts is known as a green approach, as it does not require the use of high pressure, energy, high temperature, or toxic chemicals. The approach makes use of plant extracts in a process called bioreduction, which is mediated by enzymes, proteins, amino acids, and metabolites found in bark, seed, and leaf extracts, transforming silver ions into metallic silver. This work aimed at developing silver nanoparticles (AgNPs) from Brazilian pepper, applying this green methodology. Hydroalcoholic extract of leaves of Raddi was prepared and its concentration of polyphenols, tannins, and saponins quantified. The produced nanoparticles were characterized by UV-Vis spectroscopy, thermogravimetric analysis (TG), dynamic light scattering (DLS), and zeta potential (ZP). AgNPs were formulated in sodium alginate hydrogels to obtain a nano-based semi-solid formulation for skin application. The obtained silver nanoparticles of mean size between 350 and 450 nm showed no cytotoxicity against L929 mouse fibroblasts within the concentration range of 0.025 mg/mL and 10 mg/mL. Raddi was found to enhance microbial inhibition against the tested strains, especially against gram-negative bacteria. Its potential use as an alternative to overcome bacterial resistance can be expected.
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http://dx.doi.org/10.1080/10837450.2021.1898634DOI Listing
June 2021
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