scholarly journals Clotrimazole-Loaded Mediterranean Essential Oils NLC: A Synergic Treatment of Candida Skin Infections

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 231 ◽  
Author(s):  
Claudia Carbone ◽  
Maria do Céu Teixeira ◽  
Maria do Céu Sousa ◽  
Carlos Martins-Gomes ◽  
Amelia M. Silva ◽  
...  
Keyword(s):  
Essential Oils ◽  
Cell Line ◽  
Synergistic Effects ◽  
In Vitro Release ◽  
Skin Infections ◽  
Candida Spp ◽  
Drug Effectiveness ◽  
Development Of Resistance ◽  
Calorimetric Studies

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 models, confirmed the potential antimicrobial activity of the selected oils due to their interaction with membrane permeabilization. Nanoparticles provided a prolonged in vitro release of clotrimazole. In vitro studies against Candida albicans, Candida krusei and Candida parapsilosis, showed an increase of the antifungal activity of clotrimazole-loaded nanoparticles prepared with Lavandula or Rosmarinus, thus confirming nanostructured lipid carriers (NLC) containing Mediterranean essential oils represent a promising strategy to improve drug effectiveness against topical candidiasis.

scholarly journals Design and In Vitro Study of a Dual Drug-Loaded Delivery System Produced by Electrospinning for the Treatment of Acute Injuries of the Central Nervous System

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 848
Author(s):  
Luisa Stella Dolci ◽  
Rosaria Carmela Perone ◽  
Roberto Di Gesù ◽  
Mallesh Kurakula ◽  
Chiara Gualandi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Delivery System ◽  
Synergistic Effects ◽  
In Vitro Release ◽  
Health Priorities ◽  
The Central Nervous System ◽  
Vitro Release ◽  
Dual Drug

Vascular and traumatic injuries of the central nervous system are recognized as global health priorities. A polypharmacology approach that is able to simultaneously target several injury factors by the combination of agents having synergistic effects appears to be promising. Herein, we designed a polymeric delivery system loaded with two drugs, ibuprofen (Ibu) and thyroid hormone triiodothyronine (T3) to in vitro release the suitable amount of the anti-inflammation and the remyelination drug. As a production method, electrospinning technology was used. First, Ibu-loaded micro (diameter circa 0.95–1.20 µm) and nano (diameter circa 0.70 µm) fibers were produced using poly(l-lactide) PLLA and PLGA with different lactide/glycolide ratios (50:50, 75:25, and 85:15) to select the most suitable polymer and fiber diameter. Based on the in vitro release results and in-house knowledge, PLLA nanofibers (mean diameter = 580 ± 120 nm) loaded with both Ibu and T3 were then successfully produced by a co-axial electrospinning technique. The in vitro release studies demonstrated that the final Ibu/T3 PLLA system extended the release of both drugs for 14 days, providing the target sustained release. Finally, studies in cell cultures (RAW macrophages and neural stem cell-derived oligodendrocyte precursor cells—OPCs) demonstrated the anti-inflammatory and promyelinating efficacy of the dual drug-loaded delivery platform.

scholarly journals KML001, a Telomere-Targeting Drug, Sensitizes Glioblastoma Cells to Temozolomide Chemotherapy and Radiotherapy through DNA Damage and Apoptosis

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Seon Rang Woo ◽  
Yunhee Ham ◽  
Wonyoung Kang ◽  
Heekyoung Yang ◽  
Sujong Kim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Line ◽  
Synergistic Effects ◽  
Resistant Cell Line ◽  
Therapeutic Effects ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Cytotoxic Treatment ◽  
Xenograft Models

Standard treatment for glioblastoma comprises surgical resection, chemotherapy with temozolomide, and radiotherapy. Nevertheless, majority of glioblastoma patients have recurrence from resistance to the cytotoxic conventional therapies. We examined combinational effects of KML001, an arsenic compound targeting telomeres of chromosomes with temozolomide or irradiation, in glioblastoma cell lines and xenograft models, to overcome the therapeutic limitation of chemoradiation therapy for glioblastoma. Although KML001 alone showed little effects onin vitrosurvival of glioblastoma cells, cell death byin vitrotemozolomide treatment or irradiation was synergistically potentiated by combination with KML001. Since phosphorylatedγ-H2AX, cleaved casepase-3, and cleaved PARP were dramatically increased by KML001, the synergistic effects would be mediated by increased DNA damage and subsequent tumor cell apoptosis. Combinatorial effects of KML001 were observed not only in chemo- and radiosensitive glioblastoma cell line, U87MG, but also in the resistant cell line, U251MG. In the U87MG glioblastoma xenograft models, KML001 did not have systemic toxicity but showed synergistic therapeutic effects in combination with temozolomide or irradiation to reduce tumor volumes significantly. These data indicated that KML001 could be a candidate sensitizer to potentiate therapeutic effects of conventional cytotoxic treatment for glioblastoma.

scholarly journals Essential oils against Candida spp: in vitro antifungal activity of Origanum vulgare

2013 ◽  
Vol 7 (20) ◽  
pp. 2245-2250 ◽  
Author(s):  
Brum Cleff Marlete ◽  
Madrid Isabel ◽  
Raquel Meinerz Ana ◽  
Carlos Arauacute jo Meireles Maacute rio ◽  
Roberto Braga de Mello Joatilde o ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Essential Oils ◽  
Origanum Vulgare ◽  
Candida Spp ◽  
In Vitro Antifungal Activity

scholarly journals The Splenic Microenvironment Is a Novel Site of Relapse Following ABT-199 Treatment

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3800-3800
Author(s):  
Alessandra Di Grande ◽  
Sofie Piers ◽  
Pieter Van Vlierberghe ◽  
Triona Ni Chonghaile
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Poor Prognosis ◽  
Hematologic Malignancy ◽  
Xenograft Model ◽  
Clinical Importance ◽  
Development Of Resistance ◽  
A Site

T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive hematologic malignancy arising from the transformation of immune T-cell lymphocytes. Early T-cell progenitor (ETP-ALL) is a subgroup particularly associated with a poor prognosis and a high risk for relapse. While the leukaemia initially develops in the thymus it spreads in the blood to the bone marrow, lymph nodes and often the spleen. Interestingly, splenomegaly was previously associated with a poor prognosis in leukemic patients. Recently, it was shown that ETP-ALL is dependent on the expression of the anti-apoptotic protein BCL-2, and is sensitive to inhibition with ABT-199, a BCL-2 specific BH3 mimetic. However, one issue with targeted agents, like ABT-199, is the development of resistance to treatment. Our aim was to determine potential in vivosites of resistance/relapse following ABT-199 treatment using a xenograft model of ETP-ALL. We confirmed that the ETP-ALL LOUCY cell line is BCL-2 dependent and then labelled it with luciferase to enable visualisation of the leukaemia in vivo. Following establishment of the leukaemia in NOD/SCID gamma mice, as assessed by hCD45+, the mice were randomised to receive vehicle control or 50 mg/kg ABT-199 by oral gavage daily for two weeks. While the mice were initially sensitive to ABT-199, the leukaemia started to progress while on treatment. Interestingly, there appeared to be a selective redistribution of the leukaemia to the spleen following ABT-199 treatment. Indeed, LOUCY cells isolated from the spleen of the mice had a reduced BCL-2 dependence, as assessed by BH3 profiling. The reduced BCL-2 dependence correlated with reduced BCL-2 expression at both the mRNA and protein level. Next, we confirmed that human splenic fibroblasts (HSF) co-cultured with the LOUCY cell line in vitro also altered BCL-2 dependence and expression using BH3 profiling and Western blotting. To identify potential splenic cytokines involved in the regulation of BCL-2 protein expression in ETP-ALL we performed a screening cytokine array. Upon co-culture of the LOUCY cells with HSF there was an increased expression of IL-6, this was confirmed using ELISA. Using an IL-6 receptor antibody we confirmed that blocking IL-6 receptor reversed the change in BCL-2 dependence in the presence of the splenic microenvironment. Lastly, we confirmed in a T-ALL patient-derived xenograft, that is BCL-2 dependent, that the splenic microenvironment alters the mitochondrial apoptotic threshold. Currently, there are reports in the literature of ETP-ALL patients being treated with ABT-199. While there have been numerous studies lately describing cell autonomous events leading to ABT-199 resistance, our novel finding that the splenic microenvironment is a site of relapse is potentially of great clinical importance for BCL-2 dependent leukemia's. Disclosures Ni Chonghaile: AbbVie: Research Funding.

scholarly journals In Vitro and In Vivo Anti-Candida spp. Activity of Plant-Derived Products

Plants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 494 ◽  
Author(s):  
Reginaldo dos Santos Pedroso ◽  
Brenda Lorena Balbino ◽  
Géssica Andrade ◽  
Maria Cecilia Pereira Sacardo Dias ◽  
Tavane Aparecida Alvarenga ◽  
...  
Keyword(s):  
Essential Oil ◽  
Essential Oils ◽  
Gallic Acid ◽  
Antifungal Drugs ◽  
Citrus Limon ◽  
Cupressus Sempervirens ◽  
Candida Spp ◽  
Fungistatic Activity

Candidiasis therapy, especially for candidiasis caused by Candida non-albicans species, is limited by the relatively reduced number of antifungal drugs and the emergence of antifungal tolerance. This study evaluates the anticandidal activity of 41 plant-derived products against Candida species, in both planktonic and biofilm cells. This study also evaluates the toxicity and the therapeutic action of the most active compounds by using the Caenorhabditis elegans–Candida model. The planktonic cells were cultured with various concentrations of the tested agents. The Cupressus sempervirens, Citrus limon, and Litsea cubeba essential oils as well as gallic acid were the most active anticandidal compounds. Candida cell re-growth after treatment with these agents for 48 h demonstrated that the L. cubeba essential oil and gallic acid displayed fungistatic activity, whereas the C. limon and C. sempervirens essential oils exhibited fungicidal activity. The C. sempervirens essential oil was not toxic and increased the survival of C. elegans worms infected with C. glabrata or C. orthopsilosis. All the plant-derived products assayed at 250 µg/mL affected C. krusei biofilms. The tested plant-derived products proved to be potential therapeutic agents against Candida, especially Candida non-albicans species, and should be considered when developing new anticandidal agents.

scholarly journals In Vitro Antifungal Activity of Silver Nanoparticles Biosynthesized with Beech Bark Extract

Plants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2153
Author(s):  
Anca Delia Mare ◽  
Cristina Nicoleta Ciurea ◽  
Adrian Man ◽  
Mihai Mareș ◽  
Felicia Toma ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Antifungal Activity ◽  
Germ Tube ◽  
Synergistic Effects ◽  
Bark Extract ◽  
Synergistic Activity ◽  
Tube Production ◽  
Candida Spp ◽  
Biofilm Production

Biosynthesis is a green method for the synthesis of silver nanoparticles (AgNPs). This study aimed to assess the antifungal activity of two silver nanoparticle solutions, synthesized using beech bark extract (BBE) and acetate and nitrate silver salts (AgNP Acetate BBE and AgNP Nitrate BBE), their influence on biofilm production, their potential synergistic effects with fluconazole, on different Candida spp., and their influence on virulence factors of C. albicans (germ tube production, gene expression for ALS3, SAP2, HSP70). Both the AgNP BBEs presented different minimum inhibitory concentrations for all the studied Candida spp., but biofilm production was inhibited only for C. albicans and C. guilliermondii. The growth rates of all the studied Candida spp. were inhibited in the presence of both AgNP BBEs, except for C. auris. Synergistic activity was observed for C. parapsilosis and C. guilliermondii, for different combinations of fluconazole with both the AgNP BBEs. The germ tube production of C. albicans was slightly inhibited by the AgNP BBEs. Only AgNP Acetate BBE was able to down-regulate the expression of SAP2. Overall, we can conclude that, even if more studies are necessary, AgNPs synthesized with beech bark extract might be an interesting alternative to classic antifungal treatments.

scholarly journals Chemical composition of essential oils from the apiaceae family, cytotoxicity, and their antifungal activity in vitro against candida species from oral cavity

2019 ◽  
Vol 79 (3) ◽  
pp. 432-437 ◽  
Author(s):  
J. N. Vieira ◽  
C. L. Gonçalves ◽  
J. P. V. Villarreal ◽  
V. M. Gonçalves ◽  
R. G. Lund ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Antifungal Activity ◽  
Essential Oils ◽  
Inhibitory Concentration ◽  
Anethum Graveolens ◽  
Candida Spp ◽  
Foeniculum Vulgare ◽  
Main Components ◽  
L929 Mouse

Abstract The aims of this research were: evaluate the chemical composition and the cytotoxicity of the Cuminum cyminum (cumin), Anethum graveolens (dill), Pimpinella anisum (anise) and Foeniculum vulgare (fennel) essential oils, as well as their antifungal activity in vitro against ten Candida spp. isolates. The chemical composition of the oils was analyzed by means of gas chromatography coupled with mass spectrometry (GC/MS). The cytotoxicity assays were performed, using the cell proliferation reagent WST-1 in L929 mouse fibroblasts (20x103 well-1). The determinate the Minimum Inhibitory Concentration (MIC), was performed through the Broth Microdilution technique (CLSI). The chemical main components were the cuminaldehyde (32.66%) for cumin, carvone (34.89%) for the dill, trans-anethole (94.01%) for the anise and anethole (79.62%) for the fennel. Anise and fennel did not were cytotoxic in all the tested concentrations, however the cumin oil was cytotoxic in the concentration of 20 mg.mL-1 and the dill in the concentrations of 20 and 8 mg.mL-1. All yeasts were susceptible against the evaluated essential oils. Cumin presented the lowest MIC against yeasts. We concluded that all the essential oils presented inhibitory action against Candida spp., and C . cyminum, P. anisum and F. vulgare were not cytotoxic in the same minimum inhibitory concentrations for the fungi.

scholarly journals Chitosan-Stabilized Ag Nanoparticles with Superior Biocompatibility and Their Synergistic Antibacterial Effect in Mixtures with Essential Oils

Nanomaterials ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 826 ◽  
Author(s):  
Ludmila Cinteza ◽  
Cristina Scomoroscenco ◽  
Sorina Voicu ◽  
Cristina Nistor ◽  
Sabina Nitu ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Essential Oils ◽  
Metallic Nanoparticles ◽  
Synergistic Effects ◽  
Medical Application ◽  
Colloidal Dispersion ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Promising Alternative

Silver nanoparticles (AgNPs) are considered a promising alternative to the use of antibiotics in fighting multidrug-resistant pathogens. However, their use in medical application is hindered by the public concern regarding the toxicity of metallic nanoparticles. In this study, rationally designed AgNP were produced, in order to balance the antibacterial activity and toxicity. A facile, environmentally friendly synthesis was used for the electrochemical fabrication of AgNPs. Chitosan was employed as the capping agent, both for the stabilization and to improve the biocompatibility. Size, morphology, composition, capping layer, and stability of the synthesized nanoparticles were characterized. The in vitro biocompatibility and antimicrobial activities of AgNPs against common Gram-negative and Gram-positive bacteria were evaluated. The results revealed that chitosan-stabilized AgNPs were nontoxic to normal fibroblasts, even at high concentrations, compared to bare nanoparticles, while significant antibacterial activity was recorded. The silver colloidal dispersion was further mixed with essential oils (EO) to increase the biological activity. Synergistic effects at some AgNP–EO ratios were observed, as demonstrated by the fractionary inhibitory concentration values. Our results reveal that the synergistic action of both polymer-stabilized AgNPs and essential oils could provide a significant efficiency against a large variety of microorganisms, with minimal side effects.

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