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1.
Eur J Pharm Biopharm ; 199: 114280, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38588828

RESUMO

Helicobacter pylori (H. pylori) is a microorganism directly linked to severe clinical conditions affecting the stomach. The virulence factors and its ability to form biofilms increase resistance to conventional antibiotics, growing the need for new substances and strategies for the treatment of H. pylori infection. The trans-resveratrol (RESV), a bioactive polyphenol from natural sources, has a potential activity against this gastric pathogen. Here, Chitosan nanoparticles (NP) containing RESV (RESV-NP) were developed for H. pylori management. The RESV-NP were prepared using the ionic gelation method and characterized by Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA) and, Cryogenic Transmission Electron Microscopy (Cryo - TEM). The encapsulation efficiency (EE) and in vitro release rate of RESV were quantified using high-performance liquid chromatography (HPLC). RESV-NP performance against H. pylori was evaluated by the quantification of the minimum inhibitory/bactericidal concentrations (MIC/MBC), time to kill, alterations in H. pylori morphology in its planktonic form, effects against H. pylori biofilm and in an in vitro infection model. RESV-NP cytotoxicity was evaluated against AGS and MKN-74 cell lines and by hemolysis assay. Acute toxicity was tested using Galleria mellonella model assays. RESV-NP showed a spherical shape, size of 145.3 ± 24.7 nm, polydispersity index (PDI) of 0.28 ± 0.008, and zeta potential (ZP) of + 16.9 ± 1.81 mV in DLS, while particle concentration was 3.12 x 1011 NP/mL (NTA). RESV-NP EE was 72 %, with full release within the first 5 min. In microbiological assays, RESV-NP presented a MIC/MBC of 3.9 µg/mL, a time to kill of 24 h for complete eradication of H. pylori. At a concentration of 2xMIC (7.8 µg/mL), RESV-NP completely eradicated the H. pylori biofilm, and in an in vitro infection model, RESV-NP (4xMIC - 15.6 µg/mL) showed a significant decrease in bacterial load (1 Log10CFU/mL) when compared to the H. pylori J99 control. In addition, they did not demonstrate a toxic character at MIC concentration for both cell lines. The use of the RESV-NP with mucoadhesion profile is an interesting strategy for oral administration of substances targeting gastric disorders, linked to H. pylori infections.


Assuntos
Antibacterianos , Biofilmes , Quitosana , Infecções por Helicobacter , Helicobacter pylori , Testes de Sensibilidade Microbiana , Nanopartículas , Resveratrol , Resveratrol/administração & dosagem , Resveratrol/farmacologia , Helicobacter pylori/efeitos dos fármacos , Quitosana/química , Nanopartículas/química , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Humanos , Animais , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Estilbenos/farmacologia , Estilbenos/administração & dosagem , Estilbenos/química , Tamanho da Partícula
2.
J Fungi (Basel) ; 10(4)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38667924

RESUMO

The Candida auris species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially in hospitals where outbreaks are more recurrent. In many cases, monotherapy is not effective, and drug combinations are opted for. However, resistance to antifungals has increased over the years. In view of this, nanoemulsions (NEs) may represent a nanotechnology strategy in the development of new therapeutic alternatives. Therefore, this study developed a co-encapsulated nanoemulsion with amphotericin B (AmB) and micafungin (MICA) (NEMA) for the control of infections caused by C. auris. NEs were developed in previous studies. Briefly, the NEs were composed of a mixture of 10% sunflower oil and cholesterol as the oil phase (5:1), 10% Polyoxyethylene (20) cetyl ether (Brij® 58) and soy phosphatidylcholine as surfactant/co-surfactant (2:1), and 80% PBS as the aqueous phase. The in vivo assay used BALB/c mice weighing between 25 and 28 g that were immunosuppressed (CEUA/FCF/CAr n° 29/2021) and infected with Candida auris CDC B11903. The in vivo results show the surprising potentiate of the antifungal activity of the co-encapsulated drugs in NE, preventing yeast from causing infection in the lung and thymus. Biochemical assays showed a higher concentration of liver and kidney enzymes under treatment with AmB and MICAmB. In conclusion, this combination of drugs to combat the infection caused by C. auris can be considered an efficient therapeutic option, and nanoemulsions contribute to therapeutic potentiate, proving to be a promising new alternative.

3.
Beilstein J Nanotechnol ; 15: 104-114, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38264062

RESUMO

Plant-based insecticides offer advantages such as negligible residual effects, reduced risks to both humans and the environment, and immunity to resistance issues that plague conventional chemicals. However, the practical use of monoterpenes in insect control has been hampered by challenges including their poor solubility and stability in aqueous environments. In recent years, the application of nanotechnology-based formulations, specifically nanoemulsions, has emerged as a prospective strategy to surmount these obstacles. In this study, we developed and characterized nanoemulsions based on cymene and myrcene and assessed their toxicity both in vitro using human keratinocytes (HaCAT) cells and in an in vivo model involving Galleria mellonella larvae. Additionally, we investigated the insecticidal efficacy of monoterpenes against the mosquito Aedes aegypti, the primary dengue vector, via larval bioassay. Employing a low-energy approach, we successfully generated nanoemulsions. The cymene-based nanoemulsion exhibited a hydrodynamic diameter of approximately 98 nm and a zeta potential of -25 mV. The myrcene-based nanoemulsion displayed a hydrodynamic diameter of 118 nm and a zeta potential of -20 mV. Notably, both nanoemulsions demonstrated stability over 60 days, accompanied by controlled release properties and low toxicity towards HaCAT cells and Galleria mellonella larvae. Moreover, the nanoemulsions exhibited significant lethality against third-instar Aedes aegypti larvae at a concentration of 50 mg/L. In conclusion, the utilization of nanoemulsions encapsulating cymene and myrcene presents a promising avenue for overcoming the limitations associated with poor solubility and stability of monoterpenes. This study sheds light on the potential of the nanoemulsions as effective and environmentally friendly insecticides in the ongoing battle against mosquito-borne diseases.

4.
Crit Rev Microbiol ; : 1-22, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37897442

RESUMO

Helicobacter pylori is a gram-negative, spiral-shaped, flagellated bacterium that colonizes the stomach of half the world's population. Helicobacter pylori infection causes pathologies of varying severity. Standard oral therapy fails in 15-20% since the barriers of the oral route decrease the bioavailability of antibiotics and the intrinsic factors of bacteria increase the rates of resistance. Nanoparticles and microparticles are promising strategies for drug delivery into the gastric mucosa and targeting H. pylori. The variety of building blocks creates systems with distinct colloidal, surface, and biological properties. These features improve drug-pathogen interactions, eliminate drug depletion and overuse, and enable the association of multiple actives combating H. pylori on several fronts. Nanoparticles and microparticles are successfully used to overcome the barriers of the oral route, physicochemical inconveniences, and lack of selectivity of current therapy. They have proven efficient in employing promising anti-H. pylori compounds whose limitation is oral route instability, such as some antibiotics and natural products. However, the current challenge is the applicability of these strategies in clinical practice. For this reason, strategies employing a rational design are necessary, including in the development of nano- and microsystems for the oral route.

5.
Fitoterapia ; 171: 105706, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37852387

RESUMO

The present work reports the effects of chemical elicitors and epigenetic modifiers on the production and diversification of secondary metabolites produced by Anthostomella brabeji - an endophytic fungus isolated from Paepalanthus planifolius (Eriocaulaceae). The fungus was cultivated under four different small-scale culture conditions in potato dextrose broth (PDB): PDB (control), PDB + Mg+2, PDB + Cu+2 and PDB + 5-AZA (5-azacytidine). The incorporation of Cu+2 into PDB medium yielded the most promising results as the most significant differences in the metabolic profile of A. brabeji were observed under this condition. The chemical analysis of the PDB + Cu+2 extract resulted in the isolation of seven metabolites, including three new benzofuran derivatives (2, 4 and 6) and four known compounds (1, 3, 5 and 7). The metabolites were tested using the Gram-positive bacterium Staphylococcus aureus, Gram-negative bacteria Salmonella sp. and Escherichia coli, and six yeasts of Candida albicans and non-albicans. The EtOAc extract (PDB + Cu+2), and compounds 1, 2 and 7 exhibited relevant antifungal activity against Candida spp., with minimum inhibitory concentration ranging from 62.5 to 500.0 µg/mL.


Assuntos
Ascomicetos , Eriocaulaceae , Cobre , Estrutura Molecular , Extratos Vegetais/química
6.
Pharmaceuticals (Basel) ; 16(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37631009

RESUMO

BACKGROUND: Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus Candida albicans, whose pathogenicity is associated with its morphological adaptability. To potentiate the treatment of C. albicans-induced VVC by an alternative method as photodynamic therapy (PDT), hypericin (Hy), a potent photosensitizer compound was incorporated into a nanostructured lipid carrier (NLC) and dispersed in hydrogel (HG). METHODS: After preparation of the sonication process, an NLC loaded with Hy was dispersed in HG based on Poloxamer 407 and chitosan obtaining Hy.NLC-HG. This hydrogel system was physically and chemically characterized and its in vitro and in vivo photodynamic and antifungal effects were evaluated. RESULTS: Through scanning electron microscopy, it was possible to observe a hydrogel system with a porous polymeric matrix and irregular microcavities. The Hy.NLC-HG system showed mucoadhesive properties (0.45 ± 0.08 N) and a satisfactory injectability (15.74 ± 4.75 N.mm), which indicates that it can be easily applied in the vaginal canal, in addition to a controlled and sustained Hy release profile from the NLC-HG of 28.55 ± 0.15% after 720 min. The in vitro antibiofilm assay significantly reduced the viability of C. albicans (p < 0.001) by 1.2 log10 for Hy.NLC-HG/PDT and 1.9 log10 for PS/PDT, Hy.NLC/PDT, and free RB/PDT, compared to the PBS/PDT negative control. The in vivo antifungal evaluation showed that animals treated with the vaginal cream (non-PDT) and the PDT-mediated Hy.NLC-HG system showed a significant difference of p < 0.001 in the number of C. albicans colonies (log) in the vaginal canal, compared to the inoculation control group. CONCLUSIONS: Thus, we demonstrate the pharmaceutical, antifungal, and photodynamic potential of hydrogel systems for Hy vaginal administration.

7.
Microorganisms ; 11(7)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37512799

RESUMO

Candida auris is an emerging yeast of worldwide interest due to its antifungal resistance and mortality rates. The aim of this study was to analyse the in vitro and in vivo antifungal activity of a nanoemulsion loaded with amphotericin B (NEA) against planktonic cells and biofilm of C. auris clinical isolates belonging to four different clades. In vivo assays were performed using the Galleria mellonella model to analyse antifungal activity and histopathological changes. The in vitro results showed that NEA exhibited better antifungal activity than free amphotericin B (AmB) in both planktonic and sessile cells, with >31% inhibition of mature biofilm. In the in vivo assays, NEA demonstrated superior antifungal activity in both haemolymph and tissue. NEA reduced the fungal load in the haemolymph more rapidly and with more activity in the first 24 h after infection. The histological analysis of infected larvae revealed clusters of yeast, immune cells, melanisation, and granulomas. In conclusion, NEA significantly improved the in vitro and in vivo antifungal activity of AmB and could be considered a promising therapy for C. auris infections.

8.
Nat Commun ; 14(1): 1848, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37012278

RESUMO

Coacervation via liquid-liquid phase separation provides an excellent opportunity to address the challenges of designing nanostructured biomaterials with multiple functionalities. Protein-polysaccharide coacervates, in particular, offer an appealing strategy to target biomaterial scaffolds, but these systems suffer from the low mechanical and chemical stabilities of protein-based condensates. Here we overcome these limitations by transforming native proteins into amyloid fibrils and demonstrate that the coacervation of cationic protein amyloids and anionic linear polysaccharides results in the interfacial self-assembly of biomaterials with precise control of their structure and properties. The coacervates present a highly ordered asymmetric architecture with amyloid fibrils on one side and the polysaccharide on the other. We demonstrate the excellent performance of these coacervates for gastric ulcer protection by validating via an in vivo assay their therapeutic effect as engineered microparticles. These results point at amyloid-polysaccharides coacervates as an original and effective biomaterial for multiple uses in internal medicine.


Assuntos
Amiloide , Nanoestruturas , Amiloide/química , Polissacarídeos/metabolismo , Proteínas Amiloidogênicas
9.
Med Mycol ; 61(2)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36427066

RESUMO

Fungi are becoming increasingly resistant, especially the new strains. Therefore, this work developed nanoemulsions (NE) containing micafungin (MICA), in order to improve its action against infections caused by Candida auris. The NEs were composed of the surfactants polyoxyethylene (20) cetyl ether (Brij 58®)/soy phosphatidylcholine at 10%, sunflower oil/cholesterol at 10%, and 80% PBS. The NEs were characterized by Dynamic Light Scattering (DLS). For the microbiological in vitro evaluation the determination of the minimum inhibitory concentration (MIC), ergosterol/sorbitol, time kill and biofilms tests were performed. Additionally, the antifungal activity was also evaluated in a Galleria mellonella model. The same model was used in order to evaluate acute toxicity. The NE showed a size of ∼ 42.12 nm, a polydispersion index (PDI) of 0.289, and a zeta potential (ZP) of -3.86 mV. NEM had an average size of 41.29 nm, a PDI of 0.259, and a ZP of -4.71 mV. Finally, both nanoemulsions showed good stability in a storage period of 3 months. Although NEM did not show activity in planktonic cells, it exhibited action against biofilm and in the in vivo infection model. In the alternative in vivo model assay, it was possible to observe that both, NEM and free MICA at 0.2 mg/l, was effective against the infection, being that NEM presented a better action. Finally, NEM and free MICA showed no acute toxicity up to 4 mg/l. NEM showed the best activities in in vitro in mature antibiofilm and in alternative in vivo models in G. mellonella. Although, NEs showed to be attractive for MICA transport in the treatment of infections caused by C. auris in vitro and in vivo studies with G. mellonella, further studies should be carried out, in mice, for example.


Candida auris is a fungus that can cause infections in the human body. As it is a microorganism with a high potential for resistance, it is extremely important to develop new therapeutic alternatives. Thus, nanotechnology, the science that studies materials with extremely small sizes, can be considered a promising method in the treatment of these infections.


Assuntos
Antifúngicos , Ergosterol , Animais , Camundongos , Micafungina/farmacologia , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana/veterinária , Biofilmes
10.
Crit Rev Microbiol ; 49(2): 214-230, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35634703

RESUMO

Infectious diseases are still public health problems. Microorganisms such as fungi, bacteria, viruses, and parasites are the main causing agents related to these diseases. In this context, the search for new effective strategies in prevention and/or treatment is considered essential, since current drugs often have side effects or end up, causing microbial resistance, making it a serious health problem. As an alternative to these limitations, nanotechnology has been widely used. The use of lipid-based drug delivery nanosystems (DDNs) has some advantages, such as biocompatibility, low toxicity, controlled release, the ability to carry both hydrophilic and lipophilic drugs, in addition to be easel scalable. Besides, as an improvement, studies involving the conjugation of signalling molecules on the surfaces of these nanocarriers can allow the target of certain tissues or cells. Thus, this review summarizes the performance of functionalized lipid-based DDNs for the treatment of infectious diseases caused by viruses, including SARS-CoV-2, bacteria, fungi, and parasites.


Assuntos
COVID-19 , Doenças Transmissíveis , Nanopartículas , Humanos , SARS-CoV-2 , Sistemas de Liberação de Medicamentos , Bactérias , Fungos , Doenças Transmissíveis/tratamento farmacológico , Lipídeos , Nanopartículas/uso terapêutico
11.
Molecules ; 27(23)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36500650

RESUMO

Commonly found colonizing the human microbiota, Candida albicans is a microorganism known for its ability to cause infections, mainly in the vulvovaginal region known as vulvovaginal candidiasis (VVC). This pathology is, in fact, one of the main C. albicans clinical manifestations, changing from a colonizer to a pathogen. The increase in VVC cases and limited antifungal therapy make C. albicans an increasingly frequent risk in women's lives, especially in immunocompromised patients, pregnant women and the elderly. Therefore, it is necessary to develop new therapeutic options, especially those involving natural products associated with nanotechnology, such as lycopene and mesoporous silica nanoparticles. From this perspective, this study sought to assess whether lycopene, mesoporous silica nanoparticles and their combination would be an attractive product for the treatment of this serious disease through microbiological in vitro tests and acute toxicity tests in an alternative in vivo model of Galleria mellonella. Although they did not show desirable antifungal activity for VVC therapy, the present study strongly encourages the use of mesoporous silica nanoparticles impregnated with lycopene for the treatment of other human pathologies, since the products evaluated here did not show toxicity in the in vivo test performed, being therefore, a topic to be further explored.


Assuntos
Candidíase Vulvovaginal , Fluconazol , Feminino , Humanos , Gravidez , Idoso , Candida , Dióxido de Silício/uso terapêutico , Licopeno/farmacologia , Licopeno/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans , Testes de Sensibilidade Microbiana
12.
Adv Colloid Interface Sci ; 307: 102746, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35969965

RESUMO

Pharmaceutical nanotechnology has become a trend with incalculable advantages in the applicability of systems in the controlled, safe and effective release of drugs. Among the nanotechnological nanoparticles, the mesoporous silica nanoparticles stand out, a system with significant biocompatibility, good physical chemical stability, greater surface contact area with desirable and adjustable pore structure. Once developed and well defined, these pores can carry drugs and control their release. However, to create this type of nanoparticle is essencial to use surfactants since they act as pore template. Among the most important surfactants, cetyltrimethylammonium bromide (CTAB) highlights, a quaternary ammonium compound widely used as a surfactant in the synthesis of mesoporous silica nanoparticles (MSNs), hollow mesoporous silica (HMSNs) and core-shell MSNs. However, for achieving good results of drug-loaded pores it is necessary to remove CTAB by extraction techniques, which provides pores formation throughout the silica and the incorporation of molecules. During and after the removal process, it is possible that CTAB residues remains inside the pores, despide several removal processes are described as efficient in the complete removal of surfactants. In turn, the presence of CTAB residues can be advantageous, especially when considering its antimicrobial activity. Meanwhile, it should be noted that the presence of CTAB may present high toxicity risks. This review seeks to explore not only general aspects of the use of CTAB in the synthesis of MSNs, but also to assess its toxicity in prokaryotic and eukaryotic cells, in order to determine whether CTAB residues are acceptable in MSNs that will be used as drug delivery systems for further in vivo and clinical assays.


Assuntos
Nanopartículas , Dióxido de Silício , Cetrimônio , Porosidade , Tensoativos
13.
Phytother Res ; 36(7): 2710-2745, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35643985

RESUMO

Fungal infections are one of the main public health problems, especially in immunocompromised patients, nosocomial environments, patients with chronic diseases, and transplant recipients. These diseases are increasingly frequent and lethal because the microorganism has a high capacity to acquire resistance to available therapy. The main resistance factors are the emergence of new strains and the uncontrolled use of antifungals. It is, therefore, important to develop new methods that contribute to combating fungal diseases in the clinical area. Natural products have considerable potential for the development of new drugs with antifungal activity, mainly due to their biocompatibility and low toxic effect. This promising antimicrobial activity of natural products is mainly due to the presence of flavonoids, terpenes, and quinones, which explains their antifungal potential. Pharmaceutical nanotechnology has been explored to enhance the delivery, selectivity, and clinical efficacy of these products. Nanotechnological systems provide a safe and selective environment for various substances, such as natural products, improving antifungal activity. However, further safety experiments (in vivo or clinical trials) need to be carried out to prove the therapeutic action of natural products, since they may have undesirable, toxic, and mutagenic effects. Therefore, this review article addresses the main nanotechnological methods using natural products for effective future treatment against the main fungal diseases.


Assuntos
Produtos Biológicos , Micoses , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Humanos , Micoses/tratamento farmacológico , Micoses/microbiologia , Nanomedicina , Terpenos/uso terapêutico
14.
J Mycol Med ; 32(4): 101296, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35660541

RESUMO

INTRODUCTION AND AIM: The indiscriminate use and adverse effects of the main conventional antifungal agents compromise the effectiveness of treating vulvovaginal candidiasis (VVC), mainly caused by the species Candida albicans. This study evaluated the effectiveness of photodynamic therapy (PDT) and the in vitro and in vivo anti-candida potential of the hypericin (HYP)-loaded nanostructured lipid carriers (NLC). MATERIALS AND METHODS: Empty NLC and NLC-HYP were characterized by the dynamic light scattering technique and transmission electron microscopy to evaluate the average particle size distribution and its morphologies. The in vitro inhibition photodynamic effect of the systems was tested to reduce the planktonic viability of C. albicans. The therapeutic assay photodynamic of the systems was performed to treat VVC in mice. RESULTS: Empty NLC and NLC-HYP presented values of average hydrodynamic diameter, polydispersity index, and ζ-potential from 136 to 133 nm, 0.16 to 0.22, and -18 to -30 mV, respectively, on day 30. Microscopically, the systems showed spherical morphologies and nanoscale particles. Furthermore, in the in vitro inhibition assay, the treatment of PDT with NLC-HYP (NLC-HYP+) showed a significant reduction of the C. albicans planktonic viability compared to YNB negative control after 5 min of LED light irradiation. In the in vivo therapeutic assay, the antifungal group (vaginal antifungal cream) and NLC-HYP+ evaluated in the dark and by PDT, respectively, had a significant log10 reduction in fungal burden compared to the infected group on day 8 of the VVC treatment. CONCLUSION: Due to the in vitro and in vivo anti-candida potential, PDT-mediated systems can be an effective strategy in VVC therapy.


Assuntos
Candidíase Vulvovaginal , Fotoquimioterapia , Humanos , Feminino , Camundongos , Animais , Candidíase Vulvovaginal/tratamento farmacológico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans , Candida , Lipídeos/farmacologia , Lipídeos/uso terapêutico
15.
Crit Rev Anal Chem ; 52(3): 555-576, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32880190

RESUMO

Amphotericin B (AmB) is an important antifungal agent available in the clinical practice with the action mechanism related to the inhibition of ergosterol molecule present in the fungal cell wall. Given this, in order to expand AmB knowledge, this review article gathers important information of the AmB physical, chemical, and biological properties. In addition, the main analytical methods for quantifying and determining the AmB were also reported in this review, such as high-performance liquid chromatography (HPLC), liquid chromatography, tandem mass spectrophotometry (LC-MS/MS), immunoenzymatic assay (ELISA), capillary zone electrophoresis (CE) stands out and among others. Based in this review article, the scientific community will have important information to choose the best method for analysis in their scientific or clinical research, providing greater security and reliability in the obtained results.


Assuntos
Anfotericina B , Espectrometria de Massas em Tandem , Anfotericina B/química , Anfotericina B/farmacologia , Cromatografia Líquida , Composição de Medicamentos , Reprodutibilidade dos Testes
16.
Sci Total Environ ; 807(Pt 3): 151023, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34662607

RESUMO

Galleria mellonella is a model that uses adult larvae to assess the prophylactic, therapeutic, and acute toxic potential of substances. Given their benefits, G. mellonella models are being employed in investigations of systemic infections caused by highly resistant microorganisms. Among the multiresistant microorganisms, we highlight Candida auris, a yeast with high mortality potential and resistance. Among the potential drugs, amphotericin B (AmB) stands out; however, microbial resistance episodes and side effects caused by low selectivity have been observed. The incorporation of AmB into a nanoemulsion (NE) can contribute to the control of C. auris infections and resistance as well as decrease the side effects of this drug. This study aimed to develop AmB-loaded NE (NEA) and evaluate its antifungal action against C. auris in G. mellonella. NEs were obtained by using sunflower oil and cholesterol as the oily phase, polyoxyethylene 20 cetyl ether (Brij® 58) and soy phosphatidylcholine as the surfactant system, and PBS buffer as the aqueous phase. An alternative in vivo assay with G. mellonella for acute toxicity and infection was performed using adult stage larvae (200 mg to 400 mg). According to the obtained results, NE and NEA exhibited sizes of 43 and 48 nm, respectively. The PDI was 0.285 and 0.389 for NE and NEA, respectively. The ZP showed electronegativity for both systems, with -3.77 mV and -3.80 mV for NE and NEA, respectively. Acute toxicity showed that free AmB had greater acute toxicity potential than NEA. The survival assay showed high larval viability. NEA had a better antifungal profile against systemic infection in G. mellonella. It is concluded that the alternative model proved to be an efficient in vivo assay to determine the toxicity and evaluate the therapeutic property of free AmB and NEA in systemic infections caused by C. auris.


Assuntos
Candidíase Invasiva , Mariposas , Anfotericina B/toxicidade , Animais , Antifúngicos/toxicidade , Candida auris
17.
Planta Med ; 88(5): 405-415, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33511621

RESUMO

Myrcia bella is a medicinal plant used for the treatment of diabetes, hemorrhages, and hypertension in Brazilian folk medicine. Considering that plant extracts are attractive sources of new drugs, the aim of the present study was to verify the influence of incorporating 70% hydroalcoholic of M. bella leaves in nanostructured lipid systems on the mutagenic and antifungal activities of the extract. In this work, we evaluated the antifungal potential of M. bella loaded on the microemulsion against Candida sp for minimum inhibitory concentration, using the microdilution technique. The system was composed of polyoxyethylene 20 cetyl ether and soybean phosphatidylcholine (10%), grape seed oil, cholesterol (10%: proportion 5/1), and purified water (80%). To investigate the mutagenic activity, the Ames test was used with the Salmonella Typhimurium tester strains. M. bella, either incorporated or free, showed an important antifungal effect against all tested strains. Moreover, the incorporation surprisingly inhibited the mutagenicity presented by the extract. The present study attests the antimicrobial properties of M. bella extract, contributing to the search for new natural products with biological activities and suggesting caution in its use for medicinal purposes. In addition, the results emphasize the importance of the use of nanotechnology associated with natural products as a strategy for the control of infections caused mainly by the genus Candida sp.


Assuntos
Myrtaceae , Plantas Medicinais , Antifúngicos/farmacologia , Mutagênicos , Extratos Vegetais/farmacologia
18.
Med Mycol ; 59(10): 946-957, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34137857

RESUMO

Vulvovaginal candidiasis (CVV) is a condition in which signs and symptoms are related to inflammation caused by Candida spp infection. It is the second leading cause of vaginitis in the world, representing a public health problem. The present systematic review comes with the proposal of analyze and identify the available evidence on CVV prevalence in Brazil, pointing out its variability by regions. For this, a systematic literature review was carried out with meta-analysis of cross-sectional and cohort studies, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guide recommendations, and was registered in the International Prospective Register of Systematic Reviews (PROSPERO 2020 CRD42020181695). The databases used for survey were LILACS, Scielo, Scopus, PUBMED, Web of Science and CINAHL. Fifteen studies were selected to estimate CVV prevalence in the Brazilian territory. South and Southeast regions have higher prevalences than the North and Northeast regions, no data were found for the Midwest region. The estimated prevalence for Brazil is 18%, however, it is suggested that this number is higher due to underreporting and the presence of asymptomatic cases. Therefore, new epidemiological studies are recommended throughout Brazil, to elucidate the profile of this disease in the country, in addition to assisting in the elaboration of an appropriate prevention plan by state. LAY SUMMARY: Data found in the literature regarding the epidemiological profile of vulvovaginal candidiasis in Brazil are obsolete and incomplete, so the present systematic review has the proposal to analyze and identify the evidence on vulvovaginal candidiasis prevalence in Brazil. The estimated prevalence is 18%; however, this number can be higher.


Assuntos
Candidíase Vulvovaginal , Candidíase , Animais , Brasil/epidemiologia , Candidíase/veterinária , Candidíase Vulvovaginal/epidemiologia , Candidíase Vulvovaginal/veterinária , Estudos Transversais , Feminino , Prevalência
19.
Int J Pharm ; 603: 120706, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33991597

RESUMO

The rate of infections caused by resistant bacteria to the antimicrobials available for human use grows exponentially every year, which generates major impacts on human health and the world economy. In the last two decades, human beings can witness the expressive increase in the Science and Technology worldwide, and areas such as Health Sciences have benefited from these advances in favor of human health, such as the advent of Pharmaceutical Nanotechnology as an important approach applied for bacterial infections treatment with resistance profile to available antibiotics. This review of the scientific literature brings the applicability of nanotechnology-based lipid systems as an innovative tool in the improvement of bacterial infections treatment. Important studies involving the use of liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, microemulsions and lipid nanocapsules were verified in the period from 2000 to 2020, where important scientific results were found and will serve as a basis for the use of these systems to remain in constant updating. This manuscript shows the use of these drug delivery systems as potential vehicles for antibacterial compounds, which opens a new hope in the complement of the antibacterial therapeutic arsenal. Important studies developed in the last 20 years are present in this review, and thus guarantees an update on the use of these drug delivery systems for researchers from different areas of Health Sciences.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas , Bactérias , Portadores de Fármacos , Humanos , Lipídeos , Nanotecnologia
20.
J Drug Target ; 29(10): 1029-1047, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33729081

RESUMO

Peptic ulcer disease (PUD) is a common condition that is induced by acid and pepsin causing lesions in the mucosa of the duodenum and stomach. The pathogenesis of PUD is a many-sided scenario, which involves an imbalance between protective factors, such as prostaglandins, blood flow, and cell renewal, and aggressive ones, like alcohol abuse, smoking, Helicobacter pylori colonisation, and the use of non-steroidal anti-inflammatory drugs. The standard oral treatment is well established; however, several problems can decrease the success of this therapy, such as drug degradation in the gastric environment, low oral bioavailability, and lack of vectorisation to the target site. In this way, the use of strategies to improve the effectiveness of these conventional drugs becomes interesting. Currently, the use of drug delivery systems is being explored as an option to improve the drug therapy limitations, such as antimicrobial resistance, low bioavailability, molecule degradation in an acid environment, and low concentration of the drug at the site of action. This article provides a review of oral drug delivery systems looking for improving the treatment of PUD.


Assuntos
Antiulcerosos/administração & dosagem , Sistemas de Liberação de Medicamentos , Úlcera Péptica/tratamento farmacológico , Administração Oral , Animais , Antiulcerosos/farmacocinética , Disponibilidade Biológica , Mucosa Gástrica/patologia , Humanos , Úlcera Péptica/etiologia , Úlcera Péptica/patologia , Fatores de Proteção , Fatores de Risco
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