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    Eliana B. Souto

    Abstract Nanocrystals belong to a new type of drug delivery system, consisting of a pure drug with a mean size between 100 nm and 400 nm, which has been developed to improve the dissolution properties of poorly water-soluble drugs. The... more
    Abstract Nanocrystals belong to a new type of drug delivery system, consisting of a pure drug with a mean size between 100 nm and 400 nm, which has been developed to improve the dissolution properties of poorly water-soluble drugs. The reduction of the bulk particle size down to the nanosized range offers the potential to modify the physicochemical properties of these drugs with beneficial effects on their bioavailability. Drug nanocrystals can be produced by top-down, bottom-up or via a combination of these techniques and can be used for a set of applications in healthcare. This chapter discusses the advantages and limitations of drug nanocrystals as new delivery system of poorly water-soluble drugs, revising the classical production methods, as well as new functionalization techniques and innovative applications in orthopedics, dentistry, and tissue regeneration.
    Abstract Nanotechnology is one of the most innovative scientific research fields, especially with regard to medical applications. The use of nanotechnology in medical applications is called nanomedicine and is based on the application of... more
    Abstract Nanotechnology is one of the most innovative scientific research fields, especially with regard to medical applications. The use of nanotechnology in medical applications is called nanomedicine and is based on the application of nanoparticles for diagnosis and treatment of several clinical conditions. In particular, many physicochemically distinct nanomaterials have been tested in the form of nanoparticles for cancer diagnosis and therapy. This new branch of science, in which nanotechnology is used against cancer, has been named nanooncology. Nanooncology uses materials in nanoscale to delineate the tumor margins, to separate cancer cells from healthy cells, to identify micrometastasis, and to determine if the tumor has been completely removed or not. This approach means fewer side effects and less drug use. Nanoparticles also have the potential of site-specific targeting and controlled drug release; thus, a strong dose of drug could be concentrated within a specific area, but with a planned and scheduled release, to ensure maximum effectiveness and patient safety. Although being designed to target specific organs/tissues/cells, nanoparticles may interfere with other organs/tissues, such as liver and blood. Nanoparticles can be engineered to avoid the immune system recognition or to specifically inhibit or enhance the immune responses; they are strange bodies for the immune system and may induce undesirable immunotoxicity. This chapter highlights the benefits of nanotechnology and of nanomedicines for cancer diagnosis and therapy, focusing on the relevant aspects of nanotoxicology.
    : Nanometrology has been considered as a key to the future of nanotechnology since recently. It is particularly important for nanoparticle market development that is commonly applied in dif-ferent areas of science. The adoption of... more
    : Nanometrology has been considered as a key to the future of nanotechnology since recently. It is particularly important for nanoparticle market development that is commonly applied in dif-ferent areas of science. The adoption of nanotechnologies in food and agrochemical industries represents a new frontier, with particular regard to plant defence against pathogen agents. Na-nometrology deals with a broad range of measurements, as well as chemical and structural characterization, electronic, thermal, and mechanical properties, fabrication and monitoring of nanodevices, and theoretical modelling of nanomaterials properties. Besides the scientific and technological values of a global standard offered by nanometrology, there are also several in-dustry-related values. In this paper, the most common the areas of science emphasized on the most frequently applied methods by the example of techniques/tools that have been described from a metrological standpoint at a nano size scale. Therefore, at the microscopic scale may be widely applied: optical techniques, for example, X-ray Photoelectron Spectroscopy (XPS), or op-tical transmission. Moreover, Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDX) can be used for microscopic characterization, while Scanning Probe Micros-copy (SPM), consisting of Scanning-Tunnelling Microscopy (STM) and Atomic Force Microscopy (AFM), as well as Transmission-Electron Microscopy (TEM), can be employed at the nanoscopic scale. The review has also mentioned about Secondary Ion Mass Spectroscopy (SIMS) to analyze secondary ions using a mass spectrometer. In addition, Electron Energy Loss Spectroscopy (EELS) using high-energy electrons from sample penetration or Fourier Transform Infrared Spectroscopy (FTIR) to obtain the infrared spectrum of a sample were also presented. Particle size analysis can be analyzed by performing Small-/Wide-Angle X-ray Scattering (SAXS/WAXS) and Dynamic Light Scattering (DLS) techniques. A specific metrology approach is required for most nanoparticle-based products, that is, the way nanometrology is significant for production quality control and for toxicology studies. This review wants to give an updated shot on the metrological approaches and applications, with particular attention to nanometrology for dif-ferent areas of scientific research, i.e., food, agricultural, nutraceutical, biological and medical ones. The novelty character of this paper is to discuss the application of nanotechnologies under metrological principles and approach at the interface of different integrated, multipurpose and multidisciplinary application fields. The following topics are here explored: i) metrology: defi-nitions, principles, and main features; ii) calibration methods and techniques; iii) measurement methods and systems; iv) proficiency testing; v) nanometrology. Particularly, nanometrology was highlighted in the following directions: significance of the nanodimension, nanometrology in chemical research, nanometrology for the characterization of nanoparticles, nanometrology in biological and medical sciences, mechanical nanometrology, electrical nanometrology and applications of nanometrology in agriculture and food industry.
    Atanas G. Atanasov and Dongdong Wang acknowledge the support by the Polish KNOW (Leading National Research Centre) Scientific Consortium “Healthy Animal - Safe Food,” decision of Ministry of Science and Higher Education No.... more
    Atanas G. Atanasov and Dongdong Wang acknowledge the support by the Polish KNOW (Leading National Research Centre) Scientific Consortium “Healthy Animal - Safe Food,” decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015 and the European Union under the European Regional Development Fund (Homing/2017-4/41). Antoni Sureda was supported by the Institute of Health Carlos III (Project CIBEROBN CB12/03/30038).
    The rationale for administering a drug is usually related to the increase of the drug bioavailability with the aim to achieve a therapeutic effect at a predetermined time. A drug delivery system consists of a formulation or even a device... more
    The rationale for administering a drug is usually related to the increase of the drug bioavailability with the aim to achieve a therapeutic effect at a predetermined time. A drug delivery system consists of a formulation or even a device that introduces a drug into the organism being capable of assuring the efficacy and safety by controlling the rate, time, and place of release. With the field of multifunctional nanocomposites, crucial factors such as the improvement on the medicine's efficacy, reduced economic implications, extended life of product patent, better safety and efficacy profile, and increased compliance are the aim. Nowadays, nanocomposites and nanostructured materials are important for several biotherapeutic applications, including their use in drug delivery, in orthopaedics, and in dentistry.
    The red seaweeds Grateloupia turuturu and Porphyra umbilicalis are commonly used as human food, mainly in East Asia, being valuable nutritional sources. However, studies focusing on their composition and bioactivities are scarce. Thus, G.... more
    The red seaweeds Grateloupia turuturu and Porphyra umbilicalis are commonly used as human food, mainly in East Asia, being valuable nutritional sources. However, studies focusing on their composition and bioactivities are scarce. Thus, G. turuturu and P. umbilicalis hydroethanolic and water (infusion and decoction) extracts were prepared to characterize their bioactive compounds; assess antioxidant activity against ABTS•+, •OH and •NO radicals and evaluate anti-proliferative and anti-inflammatory activities using mouse macrophage (RAW 264.7) cells. Folin–Ciocalteau results showed that G. turuturu and P. umbilicalis water extracts have fourfold and threefold, respectively, higher content in reducing compounds than hydroethanolic extracts, with the water decoctions on the richer ones (15.7 ± 0.3 and 11.9 ± 0.2 mg GAE g−1 dw, respectively; p   0.05) production inhibition capacity (~ 55%), however higher than water extracts (p < 0.05). Grateloupia turuturu water extracts produced the highest inhibition capacity against •NO production, 54–56%. RP-HPLC–DAD analysis revealed the presence of mycosporine-like amino acids (MAAs) shinorine, palythine, porphyra-334 and asterina-330 identified in both seaweeds. All extracts produced dose- and time-dependent anti-proliferative activity, being P. umbilicalis infusion extracts the most active (IC50 = 0.43 mg mL−1). At non-cytotoxic concentrations, dose-dependent anti-inflammatory activity was observed for all extracts, highlighting the P. umbilicalis hydroethanolic extract at 0.2 mg mL−1 that inhibited ~ 55% (of control) of lipopolysaccharide-induced NO release. In conclusion, G. turuturu and P. umbilicalis are rich in bioactive compounds, in particular MAAs, responsible for the bioactivities here reported, reinforcing their potential as functional food as well as sources of bioactive compounds to food and pharmaceutical industries.
    Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be loaded with active compounds entrapped within or surface-adsorbed onto the polymeric core. The term “nanoparticle” stands for both nanocapsules... more
    Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be loaded with active compounds entrapped within or surface-adsorbed onto the polymeric core. The term “nanoparticle” stands for both nanocapsules and nanospheres, which are distinguished by the morphological structure. Polymeric NPs have shown great potential for targeted delivery of drugs for the treatment of several diseases. In this review, we discuss the most commonly used methods for the production and characterization of polymeric NPs, the association efficiency of the active compound to the polymeric core, and the in vitro release mechanisms. As the safety of nanoparticles is a high priority, we also discuss the toxicology and ecotoxicology of nanoparticles to humans and to the environment.
    Abstract Nanogels are defined as colloids-based hydrogels, representing a three-dimensional network of a hydrophilic polymer in which drugs can be entrapped. Nanogels are soft, conformable, highly permeable, and stimuli-responsive... more
    Abstract Nanogels are defined as colloids-based hydrogels, representing a three-dimensional network of a hydrophilic polymer in which drugs can be entrapped. Nanogels are soft, conformable, highly permeable, and stimuli-responsive networks, which can be surface-modified with functional groups aiming at conjugation with small and large macromolecules. Nanogels also offer several advantages attributed to their capacity to absorb a significant amount of water. They can be used for targeted drug delivery and bioimaging. This review discusses the different polymers commonly in use for the production of nanogels, as well as their production methods, structural behavior, and potential biological applications.
    Medicinal plants are used worldwide due to their lower risk of side effects and eco-friendly, cost-effective production when compared to chemical drugs, encouraging researchers to further exploit the therapeutic potential of the former.... more
    Medicinal plants are used worldwide due to their lower risk of side effects and eco-friendly, cost-effective production when compared to chemical drugs, encouraging researchers to further exploit the therapeutic potential of the former. One of the most popular medicinal plants is Vitex agnus-castus L., grown in tropical and sub-tropical regions, to which different health benefits have already been attributed. In this perspective article, the in vitro and in vivo therapeutic properties of V. agnus-castus L. have been analyzed and reviewed with a special focus on its health-promoting effects and potential nutraceutical applications.
    Vegetable oils obtained from different plants are known for their beneficial effects on prophylaxis and supportive treatment of a great deal of inflammatory-mediated conditions. Their wide range of saturated and unsaturated fatty acids,... more
    Vegetable oils obtained from different plants are known for their beneficial effects on prophylaxis and supportive treatment of a great deal of inflammatory-mediated conditions. Their wide range of saturated and unsaturated fatty acids, and the presence of other ingredients (e.g., tocopherols, chlorophylls), provide them with anti-inflammatory, antioxidant and anticancer properties, which are worth being exploited. In this study, we have carried out the spectrofluorometric analysis of selected vegetable oils, namely apricot (Prunus armeniaca) kernel oil; blueberry (Vaccinium spp.) seed oil; argan (Argania spinosa) nut oil; kiwi (Actinidia deliciosa) seed oil; grape (Vitis vinifera) seed oil; evening primrose (Oenothera biennis) oil and meadowfoam (Limnanthes alba) seed oil, with the purpose to detect their fluorescent ingredients for further identification and bioactivity comparison. The obtained two- (2D) and three-dimensional (3D) emission spectra offered a complete description of...
    We have developed a new cationic solid lipid nanoparticle (SLN) formulation, composed of Compritol ATO 888, poloxamer 188 and cetyltrimethylammonium bromide (CTAB), to load perillaldehyde 1,2-epoxide, and surface-tailored with a... more
    We have developed a new cationic solid lipid nanoparticle (SLN) formulation, composed of Compritol ATO 888, poloxamer 188 and cetyltrimethylammonium bromide (CTAB), to load perillaldehyde 1,2-epoxide, and surface-tailored with a monoclonal antibody for site-specific targeting of human epithelial growth receptor 2 (HER2). Perillaldehyde 1,2-epoxide-loaded cationic SLN (cPa-SLN), with a mean particle size (z-Ave) of 275.31 ± 4.78 nm and polydispersity index (PI) of 0.303 ± 0.081, were produced by high shear homogenization. An encapsulation efficiency of cPa-SLN above 80% was achieved. The release of perillaldehyde 1,2-epoxide from cationic SLN followed the Korsemeyer–Peppas kinetic model, which is typically seen in nanoparticle formulations. The lipid peroxidation of cPa-SLN was assessed by the capacity to produce thiobarbituric acid-reactive substances, while the antioxidant activity was determined by the capacity to scavenge the stable radical DPPH. The surface functionalization of ...
    Photodynamic therapy is an innovative treatment approach broadly directed towards oncological diseases. Its applicability and efficiency are closely related to the interaction of three main components, namely a photosensitizer, light and... more
    Photodynamic therapy is an innovative treatment approach broadly directed towards oncological diseases. Its applicability and efficiency are closely related to the interaction of three main components, namely a photosensitizer, light and molecular triplet oxygen, which should drive cell death. Recently, several studies have demonstrated that squaraine cyanine dyes have a set of photophysical and photochemical properties that have made of these compounds’ potential photosensitizers for this therapeutic modality. In the present research work, we describe the synthesis and characterization of four quinoline- and benzoselenazole-derived unsymmetrical squaraine cyanine dyes. Except for the precursor of aminosquaraine dyes, i.e., O-methylated derivative, all dyes were evaluated for their behavior and absorption capacity in different organic and aqueous solvents, their ability to form singlet oxygen, their light-stability, and in vitro phototherapeutic effects against two human breast canc...
    Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chronic inflammation. The development of new therapies capable of combating vision loss involves knowledge of inflammatory retinal changes.... more
    Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chronic inflammation. The development of new therapies capable of combating vision loss involves knowledge of inflammatory retinal changes. Studies in animal models and patients with diabetes have shown a high expression of the inflammatory molecules that are involved in the progression of diabetic retinopathy. Uveal melanoma is an eye tumour that remains highly deadly, because despite the correct treatment, it still causes metastasis in about 50% of patients. This type of tumour has the ability to produce and store melanin, which may result in resistance to therapy. Over time there has been development of new therapies for this disease, such as radiotherapy and surgical resection. In this review, we discuss diabetic retinopathy and ocular melanoma, their relationship with angiogenesis and the current anti-angiogenic therapies for their treatment.
    Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have... more
    Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while...
    Genotoxicity screening tests aim to evaluate if and to what extent a compound in contact with the human body (e.g., a drug molecule, a compound from the environment) interacts with DNA. The comet assay is a sensitive method used to... more
    Genotoxicity screening tests aim to evaluate if and to what extent a compound in contact with the human body (e.g., a drug molecule, a compound from the environment) interacts with DNA. The comet assay is a sensitive method used to predict the risk of DNA damage in individual cells, as it quantifies the tape breaks, being the alkaline version (pH > 13) the most commonly used in the laboratory. Epithelial cells serve as biomatrices in genotoxicity assessments. As ca. 80% of solid cancers are of epithelial origin, the quantification of the DNA damage upon exposure of epithelial cells to a drug or drug formulation becomes relevant. Comet assays run in epithelial cells also have clinical applications in human biomonitoring, which assesses whether and to what extent is the human body exposed to environmental genotoxic compounds and how such exposure changes over time. Ocular mucosa is particularly exposed to environmental assaults. This review summarizes the published data on the geno...
    A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a... more
    A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that occurs within the pancreatic β-cells, being secreted in similar amounts as insulin. The biological activity of human C-peptide is instrumental in the prevention of diabetic neuropathy, nephropathy and other vascular complications. The main feature of type 1 diabetes mellitus is the lack of insulin and of C-peptide, but the progressive β-cell loss is also observed in later stage of type 2 diabetes mellitus. C-peptide has multifaceted effects in animals and diabetic patients due to the activation of multiple cell signalling pathways, highlighting p38 mitogen-activated protein kinase and extracellular signal–regulated kinase ½, Akt, as well as endothelial nitric oxide production. Recent works ...
    Glaucoma is a multifactorial neurodegenerative disease associated with retinal ganglion cells (RGC) loss. Increasing reports of similarities in glaucoma and other neurodegenerative conditions have led to speculation that therapies for... more
    Glaucoma is a multifactorial neurodegenerative disease associated with retinal ganglion cells (RGC) loss. Increasing reports of similarities in glaucoma and other neurodegenerative conditions have led to speculation that therapies for brain neurodegenerative disorders may also have potential as glaucoma therapies. Memantine is an N-methyl-d-aspartate (NMDA) antagonist approved for…
    Dexibuprofen-loaded PEGylated PLGA nanospheres have been developed to improve the biopharmaceutical profile of the anti-inflammatory drug for ocular administration. Dexibuprofen is the active enantiomer of ibuprofen and therefore lower... more
    Dexibuprofen-loaded PEGylated PLGA nanospheres have been developed to improve the biopharmaceutical profile of the anti-inflammatory drug for ocular administration. Dexibuprofen is the active enantiomer of ibuprofen and therefore lower doses may be applied to achieve the same therapeutic level. According to this, two batches of nanospheres of different drug concentrations, 0.5 and 1.0mg/ml respectively, have been developed (the latter corresponding to the therapeutic ibuprofen concentration for inflammatory eye diseases). Both batches were composed of negatively charged nanospheres (--14.1 and --15.9mV), with a mean particle size below 200nm, and a high encapsulation efficiency (99%). X-ray, FTIR, and DSC analyses confirmed that the drug was dispersed inside the matrix of the nanospheres. While the in vitro release profile was sustained up to 12h, the ex vivo corneal and scleral permeation profile demonstrated higher drug retention and permeation in the corneal tissue rather than in...
    Abstract Nanomaterials are systems with at least one external dimension in the size range of approximately 1–100 nm (or 10−9–10−7 m). Nanoscale modifies the chemical, physical, and biological properties of the raw material, resulting in a... more
    Abstract Nanomaterials are systems with at least one external dimension in the size range of approximately 1–100 nm (or 10−9–10−7 m). Nanoscale modifies the chemical, physical, and biological properties of the raw material, resulting in a wide diversity of applications, for example, drug delivery, diagnostics, implants, biosensors, medical imaging, and tissue engineering. Among the cosmetic and galenic formulations for topical administration, nanomaterials are being employed with the purpose of protection of the active pharmaceutical ingredient (API) from degradation, to improve the local action and to avoid the API penetration into the bloodstream, thus reducing the risk of systemic effects and toxicity. The most popular nanomaterials for topical application are based on lipid or polymeric nanoparticles, while others containing metals are mainly used for diagnostic purposes and imaging analysis. Of particular relevance are those composed of biodegradable and biocompatible raw materials (so-called nanobiomaterials), making them attractive for the formulation of topical pharmaceuticals and cosmetics. This chapter summarizes the recent advances in nanobiomaterials and their applications in galenic and cosmetic formulations.
    ABSTRACT
    The increasing development of resistance of Candida species to traditional drugs represents a great challenge to the medical field for the treatment of skin infections. Essential oils were recently proposed to increase drug effectiveness.... more
    The increasing development of resistance of Candida species to traditional drugs represents a great challenge to the medical field for the treatment of skin infections. Essential oils were recently proposed to increase drug effectiveness. Herein, we developed and optimized (23 full factorial design) Mediterranean essential oil (Rosmarinus officinalis, Lavandula x intermedia “Sumian”, Origanum vulgare subsp. hirtum) lipid nanoparticles for clotrimazole delivery, exploring the potential synergistic effects against Candida spp. Small sized nanoparticles (<100 nm) with a very broad size distribution (PDI < 0.15) and long-term stability were successfully prepared. Results of the in vitro biosafety on HaCaT (normal cell line) and A431 (tumoral cell line), allowed us to select Lavandula and Rosmarinus as anti-proliferative agents with the potential to be used as co-adjuvants in the treatment of non-tumoral proliferative dermal diseases. Results of calorimetric studies on biomembrane ...
    The aim of this work was to develop a dense lamellar scaffold, as a biomimetic material with potential applications in the regeneration of tracheal tissue after surgical tumor resection. The scaffolds were produced by plastic compression... more
    The aim of this work was to develop a dense lamellar scaffold, as a biomimetic material with potential applications in the regeneration of tracheal tissue after surgical tumor resection. The scaffolds were produced by plastic compression technique, exploiting the use of total phenolic compounds (TPC) from Psidium guajava Linn as a potential cross-linking agent in a polymeric mixture based on collagen (COL), silk fibroin (SF), and polyethylene glycol 400 (PEG 400). Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) confirmed the chemical interactions between the polymers and the cross-linking of TPC between COL and SF. Morphological analyses showed scaffolds with porosity, interconnectivity, and a porous surface structure with a gyroid-like geometry. The analysis of the anisotropic degree resulted in anisotropic structures (0.1% TFC and 0.3% TFC) and an isotropic structure (0.5% TFC). In the mechanical properties, it was evidenced greater resis...
    Gelatin-based photopolymerizable methacrylate hydrogel (GelMA) is a promising biomaterial for in situ drug delivery, while aqueous extract of Punica granatum (AEPG) peel fruit rich in gallic acid and ellagic acid is used to improve wound... more
    Gelatin-based photopolymerizable methacrylate hydrogel (GelMA) is a promising biomaterial for in situ drug delivery, while aqueous extract of Punica granatum (AEPG) peel fruit rich in gallic acid and ellagic acid is used to improve wound healing. The aim of this study was to develop and analyze the healing properties of GelMA containing AEPG, gallic acid, or ellagic acid in a rodent model. GelMA hydrogels containing 5% AEPG (GelMA-PG), 1.6% gallic acid (GelMA-GA), or 2.1% ellagic acid (GelMA-EA) were produced and their mechanical properties, enzymatic degradation, and thermogravimetric profile determined. Wound closure rates, healing histological grading, and immunohistochemical counts of myofibroblasts were assessed over time. The swelling of hydrogels varied between 50 and 90%, and GelMA exhibited a higher swelling than the other groups. The GPG samples showed higher compression and Young’s moduli than GelMA, GGA, and GAE. All samples degraded around 95% in 48 h. GPG and GGA signi...
    Opuntia ficus-indica (OFI), widely recognized as prickly pear, is a native species from Mexico, being also widely distributed in many other geographical regions worldwide. OFI is a plant with numerous beneficial properties, provide that... more
    Opuntia ficus-indica (OFI), widely recognized as prickly pear, is a native species from Mexico, being also widely distributed in many other geographical regions worldwide. OFI is a plant with numerous beneficial properties, provide that it is a source of dietary fibres, vitamins and many other bioactive compounds with anti-inflammatory, hypoglycemic and antimicrobial properties. Various parts of this plant including the fruit pulp and peel, cladode, and seeds are scientifically proven to have therapeutic potentials and are safe for human use. The bibliometric map of the works published since 2020 dealing with all aspects of OFI in the field of pharmacology, toxicology and pharmaceutics was generated, depicting the network of publications covering its ethnopharmacology, pharmacological properties, besides the extensive chemical characterization of the extracts, human and non-human uses, in vitro and in vivo studies, besides in silico tools. In this work, we review the scientific lite...
    The aim of this study was the development of a cereal bar based on bee pollen (BP), honey (H), and flour by-products (peel passion fruit flour—PPFF), generating an innovative product. BP is a protein-rich ingredient and can be used in the... more
    The aim of this study was the development of a cereal bar based on bee pollen (BP), honey (H), and flour by-products (peel passion fruit flour—PPFF), generating an innovative product. BP is a protein-rich ingredient and can be used in the composition of cereal bars. PPFF is a by-product rich in fibers. The formulations were developed using a 23 factorial design with four replicates in the center point, studying the sensory analysis as a response variable. The texture and nutritional parameters were performed for the optimal formulation. BP showed ca. 15% of protein. The final formulation (10.35% BP, 6.8% PPFF, and 25% H) presented 22.2% moisture, 1.8% ash, 0.4% total fat, 3.0% fiber, 63.1% carbohydrates, and 74.0 Kcal/25 g. The sensory analysis presented valued around 7 (typical of a traditional bar). Regarding the possibility of purchasing the product, 51% of the panelists said they would probably buy the developed product. The formulated cereal bar had a similar composition as tho...
    Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the... more
    Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with...
    Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is known to increase the risk of age-related macular degeneration (AMD). AMD is commonly categorized in two distinct types, namely, the... more
    Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is known to increase the risk of age-related macular degeneration (AMD). AMD is commonly categorized in two distinct types, namely, the nonexudative (dry form) and the exudative (wet form). Currently, there is no ideal treatment available for AMD. Recommended standard treatments are based on the use of vascular endothelial growth factor (VEGF), with the disadvantage of requiring repeated intravitreal injections which hinder patient’s compliance to the therapy. In recent years, several synthetic and natural active compounds have been proposed as innovative therapeutic strategies against this disease. There is a growing interest in the development of formulations based on nanotechnology because of its important role in the management of posterior eye segment disorders, without the use of intravitreal injections, and furthermore, with the potential to prolong drug release and thus reduce adverse...
    Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are receiving increasing interest as an approach to encapsulate natural extracts to increase the physicochemical stability of bioactives. Cannabis extract-derived... more
    Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are receiving increasing interest as an approach to encapsulate natural extracts to increase the physicochemical stability of bioactives. Cannabis extract-derived cannabidiol (CBD) has potent therapeutic properties, including anti-inflammatory, antioxidant, and neuroprotective properties. In this work, physicochemical characterization was carried out after producing Compritol-based nanoparticles (cSLN or cNLC) loaded with CBD. Then, the determination of the encapsulation efficiency (EE), loading capacity (LC), particle size (Z-Ave), polydispersity index (PDI), and zeta potential were performed. Additionally, the viscoelastic profiles and differential scanning calorimetry (DSC) patterns were recorded. As a result, CBD-loaded SLN showed a mean particle size of 217.2 ± 6.5 nm, PDI of 0.273 ± 0.023, and EE of about 74%, while CBD-loaded NLC showed Z-Ave of 158.3 ± 6.6 nm, PDI of 0.325 ± 0.016, and EE of about 70%. T...
    Commonly used clinical strategies against coronavirus disease 19 (COVID-19), including the potential role of monoclonal antibodies for site-specific targeted drug delivery, are discussed here. Solid lipid nanoparticles (SLN) tailored with... more
    Commonly used clinical strategies against coronavirus disease 19 (COVID-19), including the potential role of monoclonal antibodies for site-specific targeted drug delivery, are discussed here. Solid lipid nanoparticles (SLN) tailored with tocilizumab (TCZ) and loading cannabidiol (CBD) are proposed for the treatment of COVID-19 by oral route. TCZ, as a humanized IgG1 monoclonal antibody and an interleukin-6 (IL-6) receptor agonist, can attenuate cytokine storm in patients infected with SARS-CoV-2. CBD (an anti-inflammatory cannabinoid and TCZ agonist) alleviates anxiety, schizophrenia, and depression. CBD, obtained from Cannabis sativa L., is known to modulate gene expression and inflammation and also shows anti-cancer and anti-inflammatory properties. It has also been recognized to modulate angiotensin-converting enzyme II (ACE2) expression in SARS-CoV-2 target tissues. It has already been proven that immunosuppressive drugs targeting the IL-6 receptor may ameliorate lethal inflamm...
    Traditional medicine uses resin oils extracted from plants of the genus Copaifera for several purposes. Resin oils are being studied to understand and profile their pharmacological properties. The aim of this work was to prepare and to... more
    Traditional medicine uses resin oils extracted from plants of the genus Copaifera for several purposes. Resin oils are being studied to understand and profile their pharmacological properties. The aim of this work was to prepare and to characterize conventional and pegylated liposomes incorporating resin oils or the hexanic extract obtained from Copaifera sabulicola (copaiba) leaves. The cytotoxic effect of these products was also investigated. Conventional and stealth liposomes with copaiba extract showed similar average diameters (around 126 nm), encapsulation efficiencies greater than 75% and were stable for 90 days. A cytotoxicity test was performed on murine glioma cells and the developed liposomes presented antiproliferative action against these cancer cells at the average concentration of 30 μg/mL. Phytochemicals encapsulated in PEGylated liposomes induced greater reduction in the viability of tumor cells. In addition, bioassay-s measured the cytotoxicity of copaiba resin oil...
    Plants are the source of a large spectrum of phytochemicals, and the combined and concerted action of biologically active compounds lead to the potential beneficial properties of each plant matrix. A great attention is being addressed... more
    Plants are the source of a large spectrum of phytochemicals, and the combined and concerted action of biologically active compounds lead to the potential beneficial properties of each plant matrix. A great attention is being addressed over the years toward herbs and medicinal plants. Dragon’s Blood is a reddish resin oil extracted from Croton lechleri tree. It has been extensively used by indigenous cultures of the Amazon River since ancient times due to the beneficial nutraceutical and pharmaceutical properties. This perspective aims at providing a current framework on Dragon’s Blood with focus on antioxidant properties for nutraceuticals and pharmaceuticals in a novelty integrated and multidisciplinary manner, highlighting the current knowledge, the main research lines, and emerging strategies. A literature quantitative research analysis approach was applied as starting point. The literature search was carried out by means of the Scopus database; 365 documents have been retrieved ...
    This study evaluated the neuroprotective effects of the Africanized bee venom (BV) and its mechanisms of action after 6-hydroxydopamine-(6-OHDA)-induced lesion in a mice model. Prior to BV treatment, mice received intrastriatal... more
    This study evaluated the neuroprotective effects of the Africanized bee venom (BV) and its mechanisms of action after 6-hydroxydopamine-(6-OHDA)-induced lesion in a mice model. Prior to BV treatment, mice received intrastriatal microinjections of 6-OHDA (no induced dopaminergic neuronal death) or ascorbate saline (as a control). BV was administered subcutaneously at different dosages (0.01, 0.05 or 0.1 mg·Kg−1) once every two days over a period of 3 weeks. The open field test was carried out, together with the immunohistochemical and histopathological analysis. The chemical composition of BV was also assessed, identifying the highest concentrations of apamin, phospholipase A2 and melittin. In the behavioral evaluation, the BV (0.1 mg·Kg−1) counteracted the 6-OHDA-induced decrease in crossings and rearing. 6-OHDA caused loss of dopaminergic cell bodies in the substantia nigra pars compacta and fibers in striatum (STR). Mice that received 0.01 mg·Kg−1 showed significant increase in th...
    The Himatanthus genus presents anti-inflammatory, antioxidant activities, suggesting potential wound-healing properties. This study aimed to develop and analyze the wound-healing properties of a photopolymerizable gelatin-based hydrogel... more
    The Himatanthus genus presents anti-inflammatory, antioxidant activities, suggesting potential wound-healing properties. This study aimed to develop and analyze the wound-healing properties of a photopolymerizable gelatin-based hydrogel (GelMA) containing an ethanolic extract of Himatanthus bracteatus in a murine model. The extract was obtained under high pressure conditions, incorporated (2%) into the GelMA (GelMA-HB), and physically characterized. The anti-inflammatory activity of the extract was assessed using a carrageenan-induced pleurisy model and the GelMA-HB scarring properties in a wound-healing assay. The extract reduced IL-1β and TNF-α levels (48.5 ± 6.7 and 64.1 ± 4.9 pg/mL) compared to the vehicle (94.4 ± 2.3 pg/mL and 106.3 ± 5.7 pg/mL; p < 0.001). GelMA-HB depicted significantly lower swelling and increased resistance to mechanical compression compared to GelMA (p < 0.05). GelMA-HB accelerated wound closure over the time course of the experiment (p < 0.05) an...
    The insect Plutella xylostella is known worldwide to cause severe damage to brassica plantations because of its resistance against several groups of chemicals and pesticides. Efforts have been conducted to overcome the barrier of P.... more
    The insect Plutella xylostella is known worldwide to cause severe damage to brassica plantations because of its resistance against several groups of chemicals and pesticides. Efforts have been conducted to overcome the barrier of P. xylostella genetic resistance. Because of their easy production and effective insecticidal activity against different insect orders, silver nanoparticles are proposed as an alternative for agricultural pest control. The use of entomopathogenic fungi for nanoparticle production may offer additional advantages since fungal biomolecules may synergistically improve the nanoparticle’s effectiveness. The present study aimed to synthesize silver nanoparticles using aqueous extracts of Beauveria bassiana, Metarhizium anisopliae, and Isaria fumosorosea isolates and to evaluate their insecticidal activity against P. xylostella, as innovative nano-ecofriendly pest control. The produced silver nanoparticles were evaluated by measuring the UV–vis spectrum and the mea...
    Wound healing is known to be a complicated and intricate process and commonly classified as chronic or acute. Patients with chronic wounds are of public health concern, and require more attention onto skin lesions, including atopic... more
    Wound healing is known to be a complicated and intricate process and commonly classified as chronic or acute. Patients with chronic wounds are of public health concern, and require more attention onto skin lesions, including atopic dermatitis. Despite being a natural process, healing can be impaired by existing chronic de diseases such as diabetes, for example. Recently, wound dressings based in nanotechnology systems have emerged as a viable option to improve the healing process. Current advances in nanotechnology-based systems to release growth factors and bioactive agents represent a great opportunity to develop new therapies for wound treatments. It is essential that healthcare professionals understand the key processes involved in the healing cascade, to maximize care with these patients and minimize the undesirable outcomes of non-healing wounds. Therefore, this review aims to summarize the healing process phases and provide a general overview of dressings based in nanotechnol...
    This paper presents a comprehensive review of the main types of vaccines approaching production technology, regulatory parameters, and the quality control of vaccines. Bioinformatic tools and computational strategies have been used in the... more
    This paper presents a comprehensive review of the main types of vaccines approaching production technology, regulatory parameters, and the quality control of vaccines. Bioinformatic tools and computational strategies have been used in the research and development of new pharmaceutical products, reducing the time between supposed pharmaceutical product candidates (R&D steps) and final products (to be marketed). In fact, in the reverse vaccinology field, in silico studies can be very useful in identifying possible vaccine targets from databases. In addition, in some cases (subunit or RNA/ DNA vaccines), the in silico approach permits: (I) the evaluation of protein immunogenicity through the prediction of epitopes, (II) the potential adverse effects of antigens through the projection of similarity to host proteins, (III) toxicity and (IV) allergenicity, contributing to obtaining safe, effective, stable, and economical vaccines for existing and emerging infectious pathogens. Additionall...
    Abstract This chapter gives an updated shot on cold pressed argan (Argania spinose) oil. In addition to the description of extraction and processing technique, the main components of nutritional and nutraceutical interest of cold pressed... more
    Abstract This chapter gives an updated shot on cold pressed argan (Argania spinose) oil. In addition to the description of extraction and processing technique, the main components of nutritional and nutraceutical interest of cold pressed argan (Argania spinose) seed oil are discussed. The presence of aromatic compounds and their contribution to the organoleptic properties, as well as the beneficial properties, are discussed. Applications, with particular attention to the cosmetic field, are identified, and example of innovative green analytical techniques for adulteration detection, i.e., spectroscopy combined with advanced chemometrics is presented.
    Abstract Lipid nanoparticles are widely explored in many therapeutic, targeting, and imaging areas. Among the various nanoplatforms, lipid-based nanostructures offer better attributes to drug delivery, such as high loading capacity,... more
    Abstract Lipid nanoparticles are widely explored in many therapeutic, targeting, and imaging areas. Among the various nanoplatforms, lipid-based nanostructures offer better attributes to drug delivery, such as high loading capacity, biocompatibility, improved physicochemical and long-term stability, ease of surface modification, adjustable drug release, and enhanced bioavailability. Despite the extensive number of publications focusing on the development of lipid nanoparticles, very limited research data is available on the understanding of role of excipients. Changes in the qualitative and quantitative composition of excipients, for example, optimized hydrophilic–lipophilic balance, lipids, and lipid/surfactants combinations can make formulation development easier. This chapter discusses the role of excipients in the production of lipid nanoparticles. An overview of commonly used and upcoming promising excipients, which can facilitates formulation development of lipid nanoparticles, is discussed. A review of new research outcomes and market status of lipid nanoparticles is also addressed in the end of chapter.

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