Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 48
Filter
1.
ACS Appl Electron Mater ; 5(9): 5025-5031, 2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37779889

ABSTRACT

Resistive random access memories (RRAM), based on the formation and rupture of conductive nanoscale filaments, have attracted increased attention for application in neuromorphic and in-memory computing. However, this technology is, in part, limited by its variability, which originates from the stochastic formation and extreme heating of its nanoscale filaments. In this study, we used scanning thermal microscopy (SThM) to assess the effect of filament-induced heat spreading on the surface of metal oxide RRAMs with different device designs. We evaluate the variability of TiO2 RRAM devices with area sizes of 2 × 2 and 5 × 5 µm2. Electrical characterization shows that the variability indicated by the standard deviation of the forming voltage is ∼2 times larger for 5 × 5 µm2 devices than for the 2 × 2 µm2 ones. Further knowledge on the reason for this variability is gained through the SThM thermal maps. These maps show that for 2 × 2 µm2 devices the formation of one filament, i.e., hot spot at the device surface, happens reliably at the same location, while the filament location varies for the 5 × 5 µm2 devices. The thermal information, combined with the electrical, interfacial, and geometric characteristics of the device, provides additional insights into the operation and variability of RRAMs. This work suggests thermal engineering and characterization routes to optimize the efficiency and reliability of these devices.

2.
Molecules ; 28(10)2023 May 13.
Article in English | MEDLINE | ID: mdl-37241815

ABSTRACT

The emergence of multiresistant bacteria and the shortage of antibacterials in the drug pipeline creates the need to search for novel agents. Evolution drives the optimization of the structure of marine natural products to act as antibacterial agents. Polyketides are a vast and structurally diverse family of compounds that have been isolated from different marine microorganisms. Within the different polyketides, benzophenones, diphenyl ethers, anthraquinones, and xanthones have shown promising antibacterial activity. In this work, a dataset of 246 marine polyketides has been identified. In order to characterize the chemical space occupied by these marine polyketides, molecular descriptors and fingerprints were calculated. Molecular descriptors were analyzed according to the scaffold, and principal component analysis was performed to identify the relationships among the different descriptors. Generally, the identified marine polyketides are unsaturated, water-insoluble compounds. Among the different polyketides, diphenyl ethers tend to be more lipophilic and non-polar than the remaining classes. Molecular fingerprints were used to group the polyketides according to their molecular similarity into clusters. A total of 76 clusters were obtained, with a loose threshold for the Butina clustering algorithm, highlighting the large structural diversity of the marine polyketides. The large structural diversity was also evidenced by the visualization trees map assembled using the tree map (TMAP) unsupervised machine-learning method. The available antibacterial activity data were examined in terms of bacterial strains, and the activity data were used to rank the compounds according to their antibacterial potential. This potential ranking was used to identify the most promising compounds (four compounds) which can inspire the development of new structural analogs with better potency and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties.


Subject(s)
Polyketides , Xanthones , Xanthones/chemistry , Benzophenones/chemistry , Anthraquinones , Phenyl Ethers , Anti-Bacterial Agents/chemistry , Polyketides/chemistry
3.
Mar Drugs ; 20(1)2022 Jan 08.
Article in English | MEDLINE | ID: mdl-35049913

ABSTRACT

The marine environment is an important source of specialized metabolites with valuable biological activities. Xanthones are a relevant chemical class of specialized metabolites found in this environment due to their structural variety and their biological activities. In this work, a comprehensive literature review of marine xanthones reported up to now was performed. A large number of bioactive xanthone derivatives (169) were identified, and their structures, biological activities, and natural sources were described. To characterize the chemical space occupied by marine-derived xanthones, molecular descriptors were calculated. For the analysis of the molecular descriptors, the xanthone derivatives were grouped into five structural categories (simple, prenylated, O-heterocyclic, complex, and hydroxanthones) and six biological activities (antitumor, antibacterial, antidiabetic, antifungal, antiviral, and miscellaneous). Moreover, the natural product-likeness and the drug-likeness of marine xanthones were also assessed. Marine xanthone derivatives are rewarding bioactive compounds and constitute a promising starting point for the design of other novel bioactive molecules.


Subject(s)
Xanthones/chemistry , Animals , Aquatic Organisms , Drug Design , Structure-Activity Relationship
4.
Molecules ; 25(24)2020 Dec 10.
Article in English | MEDLINE | ID: mdl-33322077

ABSTRACT

Microtubule-targeting agents (MTAs) remain a gold standard for the treatment of several cancer types. By interfering with microtubules dynamic, MTAs induce a mitotic arrest followed by cell death. This antimitotic activity of MTAs is dependent on the spindle assembly checkpoint (SAC), which monitors the integrity of the mitotic spindle and proper chromosome attachments to microtubules in order to ensure accurate chromosome segregation and timely anaphase onset. However, the cytotoxic activity of MTAs is restrained by drug resistance and/or toxicities, and had motivated the search for new compounds and/or alternative therapeutic strategies. Here, we describe the synthesis and mechanism of action of the xanthone derivative pyranoxanthone 2 that exhibits a potent anti-growth activity against cancer cells. We found that cancer cells treated with the pyranoxanthone 2 exhibited persistent defects in chromosome congression during mitosis that were not corrected over time, which induced a prolonged SAC-dependent mitotic arrest followed by massive apoptosis. Importantly, pyranoxanthone 2 was able to potentiate apoptosis of cancer cells treated with nanomolar concentrations of paclitaxel. Our data identified the potential of the pyranoxanthone 2 as a new potent antimitotic with promising antitumor potential, either alone or in combination regimens.


Subject(s)
Antimitotic Agents/chemistry , Antimitotic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Pyrans/chemistry , Xanthones/chemistry , Xanthones/pharmacology , Antimitotic Agents/chemical synthesis , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Cycle Checkpoints , Cell Line, Tumor , Chemistry Techniques, Synthetic , Chromosome Aberrations/drug effects , Fluorescent Antibody Technique , Humans , M Phase Cell Cycle Checkpoints/drug effects , Microtubules/metabolism , Mitosis/drug effects , Molecular Structure , Paclitaxel/pharmacology
5.
Int J Biol Macromol ; 158: 180-188, 2020 Apr 30.
Article in English | MEDLINE | ID: mdl-32360466

ABSTRACT

Considering the potential of mucoadhesive properties of nanoparticles in oral delivery, this work describes the preparation and characterization of fucoidan/chitosan nanoparticles loaded with methotrexate (MTX) intended to lung cancer therapy. The nanoparticles were produced and characterized in terms of size, surface charge, entrapment efficiency, and morphology. The size of the developed nanoparticles was around 300 nm, the zeta potential value was negative (ca. -30 mV), revealing a low tendency to aggregate. The self-assembled fucoidan/chitosan nanoparticles were stable at acidic pH (1.6-5.2), without disintegration under pH 6-7.4, revealing resistance through the gastrointestinal tract, and were found to be mucoadhesive suggesting ability to enhance drug oral bioavailability. Lung cancer cells quickly internalized the developed nanoparticles. Moreover, MTX-loaded fucoidan/chitosan nanoparticles up to 245 µg mL-1 in polymer equivalent to 23.5 µg mL-1 of MTX were safe towards fibroblasts but hampered lung cancer cell proliferation mediated by an apoptotic process. MTX-loaded nanoparticles were 7-fold more effective in inhibiting lung cancer cells proliferation than the free drug, showing the potential of fucoidan-chitosan nanoparticles to improve the cytotoxicity of free methotrexate on A549 lung cancer cells. These results also demonstrate that fucoidan/chitosan nanoparticles may provide a suitable platform for poor-water soluble compounds' oral delivery.

6.
ChemMedChem ; 15(9): 749-755, 2020 05 06.
Article in English | MEDLINE | ID: mdl-32162478

ABSTRACT

Natural products have always been an important source of new hits and leads in drug discovery, with the marine environment being regarded as a significant source of novel and exquisite bioactive compounds. Yicathins B and C are two marine-derived xanthones that have shown antibacterial and antifungal activity. Herein, the total synthesis of these yicathins and six novel analogues is reported for the first time. As marine natural products tend to have very lipophilic scaffolds, the lipophilicity of yicathins and their analogues was evaluated in the classical octanol/water system and a biomimetic model-based system. As the xanthonic nucleus is a "privileged structure", other biological activities were evaluated, namely antitumor and anti-inflammatory activities. An interesting anti-inflammatory activity was identified for yicathin analogues that paves the way for the design of dual activity (anti-infective and anti-inflammatory) marine-inspired xanthone derivatives.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Macrophages/drug effects , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Discovery , Drug Screening Assays, Antitumor , Humans , Hydrophobic and Hydrophilic Interactions , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Molecular Structure , Stereoisomerism
7.
Nanoscale ; 11(36): 16978-16990, 2019 Sep 28.
Article in English | MEDLINE | ID: mdl-31498350

ABSTRACT

The resistive switching in metal-oxide thin films typically occurs via modulation of the oxygen content in nano-sized conductive filaments. For Ta2O5-based resistive switching devices, the two current models consider filaments composed of oxygen vacancies and those containing metallic Ta clusters. The present work tries to resolve this dispute. The filaments in Ta2O5 were formerly shown to exhibit the same electrical transport mechanisms as TaOx thin films with x∼ 1.0. In this paper, sputtered thin films of pure ß-Ta and of TaOx with different oxygen concentrations are studied and compared in terms of their structure and electrical transport. The structural analysis reveals the presence of Ta clusters in the TaOx films. Identical electrical transport characteristics were observed in the TaOx films with x∼ 1.0 and in the ß-Ta film. Both show the same transport mechanism, a carrier concentration on the order of 1022 cm-3 and a positive magnetoresistance associated with weak antilocalization at T < 30 K. It is concluded that the electrical transport in the TaOx films with x∼ 1.0 is dominated by percolation through Ta clusters. This means that the transport in the filaments is also determined by percolation through Ta clusters, strongly supporting the metallic Ta filament model.

8.
Molecules ; 24(2)2019 Jan 10.
Article in English | MEDLINE | ID: mdl-30634698

ABSTRACT

Marine organisms represent almost half of total biodiversity and are a very important source of new bioactive substances. Within the varied biological activities found in marine products, their antimicrobial activity is one of the most relevant. Infectious diseases are responsible for high levels of morbidity and mortality and many antimicrobials lose their effectiveness with time due to the development of resistance. These facts justify the high importance of finding new, effective and safe anti-infective agents. Among the variety of biological activities of marine xanthone derivatives, one that must be highlighted is their anti-infective properties. In this work, a literature review of marine xanthones with anti-infective activity, namely antibacterial, antifungal, antiparasitic and antiviral, is presented. Their structures, biological activity, sources and the methods used for bioactivity evaluation are described. The xanthone derivatives are grouped in three sets: xanthones, hydroxanthones and glycosylated derivatives. Moreover, molecular descriptors, biophysico-chemical properties, and pharmacokinetic parameters were calculated, and the chemical space occupied by marine xanthone derivatives is recognized. The chemical space was compared with marketed drugs and framed accordingly to the drug-likeness concept in order to profile the pharmacokinetic of anti-infective marine xanthone derivatives.


Subject(s)
Anti-Infective Agents/pharmacology , Aquatic Organisms/chemistry , Xanthones/chemistry , Xanthones/pharmacology , Animals , Anti-Infective Agents/chemistry , Biological Products/chemistry , Biological Products/pharmacology , Drug Design , Humans , Molecular Structure
9.
J Vasc Res ; 55(4): 203-209, 2018.
Article in English | MEDLINE | ID: mdl-30001541

ABSTRACT

BACKGROUND AND AIMS: Fructose intake is directly related to vascular dysfunction and it is a risk factor for the development of metabolic and cardiovascular diseases, such as obesity, diabetes, and hypertension. Selenium, a component of antioxidant enzymes, improves hyperglycemia and vascular function in diabetic animals. The aim of this study was to evaluate the effects of dietary selenium supplementation on microcirculatory and metabolic parameters of fructose-fed hamsters. METHODS AND RESULTS: Male hamsters (Mesocricetus auratus) had their drinking water substituted or not by 10% fructose solution for 60 days, during which their microcirculatory function was evaluated in the cheek pouch preparation. Blood glucose and serum insulin levels were also tested. Microcirculatory responses to acetylcholine (an endothelium-dependent vasodilator) and to sodium nitroprusside (SNP, an endothelium-independent vasodilator), and macromolecular permeability increase induced by a 30-min ischemia/reperfusion (I/R) procedure, showed that endothelium-dependent and independent vasodilatation was significantly increased in animals that had high selenium supplementation, in both the control and fructose-fed groups. Selenium supplementation protected against plasma leakage induced by I/R in all control and fructose-fed groups. CONCLUSION: Our results indicate that dietary selenium supplementation reduces microvascular dysfunction by increasing endothelial-dependent and independent dilatation and reducing macromolecular permeability increase in fructose-fed animals.


Subject(s)
Fructose/administration & dosage , Microcirculation/drug effects , Selenium/administration & dosage , Acetylcholine/pharmacology , Animals , Blood Glucose/analysis , Capillary Permeability/drug effects , Cheek/blood supply , Cricetinae , Dietary Supplements , Drinking , Endothelium, Vascular/physiology , Fructose/adverse effects , Insulin/blood , Male , Mesocricetus , Microcirculation/physiology , Nitroprusside/pharmacology , Reperfusion Injury , Vasodilation/drug effects , Vasodilator Agents/pharmacology
10.
Eur J Pharm Sci ; 115: 369-380, 2018 Mar 30.
Article in English | MEDLINE | ID: mdl-29366962

ABSTRACT

Lipophilicity is a physicochemical property of crucial importance in drug discovery and drug design. Biomimetic models, such as liposomes and micelles, constitute a valuable tool for the assessment of lipophilicity through the determination of partition coefficients (log Kp). However, the lack of standardization hampers the judgment about which model or method has the best and broadest passive drug permeation predictive capacity. This work provides a comparative analysis between the methodologies based on biomimetic models to determine the partition coefficient (log Kp). For that purpose, a set of reference substances preconized by the Organization for Economic Cooperation and Development (OECD) guidelines was used. The biomimetic models employed were liposomes and micelles composed by 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) and hexadecylphosphocholine (HePC), respectively. Both lipids were used as representative phospholipids of natural membranes. The partition coefficients between biomimetic models and aqueous phases were determined by derivative spectroscopy at physiological conditions (37 °C and pH 7.4). The partition coefficients obtained using biomimetic models are quite different and more reliable than the ones obtained using an octanol/water system. Comparing the performance of the two biomimetic models, micelles revealed to be suitable only for substances with high molar absorption coefficient and log Kp > 3, but in general liposomes are the best model for accessing lipophilicity of drugs. Furthermore, a comparison between experimental data and the partition coefficients determined by the computational method COSMOmic is also provided and discussed. As a final summarizing result, a decision tree is provided in order to guide the selection of a tool for assessing the lipophilicity of drugs.


Subject(s)
Liposomes/chemistry , Pharmaceutical Preparations/chemistry , Biomimetics/methods , Dimyristoylphosphatidylcholine/chemistry , Lipids/chemistry , Micelles , Octanols/chemistry , Phospholipids/chemistry , Water/chemistry
11.
Lasers Med Sci ; 33(1): 11-18, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28840431

ABSTRACT

Oral mucositis is an acute toxicity that occurs in patients submitted to chemoradiotherapy to treat head and neck squamous cell carcinoma. In this study, we evaluated differences in gene expression in the keratinocytes of the oral mucosa of patients treated with photobiomodulation therapy and tried to associate the molecular mechanisms with clinical findings. From June 2009 to December 2010, 27 patients were included in a randomized double-blind pilot study. Buccal smears from 13 patients were obtained at days 1 and 10 of chemoradiotherapy, and overall gene expression of samples from both dates were analyzed by complementary DNA (cDNA) microarray. In addition, samples from other 14 patients were also collected at D1 and D10 of chemoradiotherapy for subsequent validation of cDNA microarray findings by qPCR. The expression array analysis identified 105 upregulated and 60 downregulated genes in our post-treatment samples when compared with controls. Among the upregulated genes with the highest fold change, it was interesting to observe the presence of genes related to keratinocyte differentiation. Among downregulated genes were observed genes related to cytotoxicity and immune response. The results indicate that genes known to be induced during differentiation of human epidermal keratinocytes were upregulated while genes associated with cytotoxicity and immune response were downregulated in the laser group. These results support previous clinical findings indicating that the lower incidence of oral mucositis associated with photobiomodulation therapy might be correlated to the activation of genes involved in keratinocyte differentiation.


Subject(s)
Chemoradiotherapy , DNA, Complementary/genetics , Keratinocytes/metabolism , Low-Level Light Therapy , Microarray Analysis/methods , Mouth Mucosa/radiation effects , Double-Blind Method , Female , Gene Expression Profiling , Gene Expression Regulation , Humans , Male , Middle Aged , Pilot Projects , Stomatitis/etiology , Stomatitis/genetics
12.
Oral Oncol ; 71: 11-15, 2017 08.
Article in English | MEDLINE | ID: mdl-28688677

ABSTRACT

BACKGROUND: The impact of low-level laser therapy (LLLT) to prevent oral mucositis in patients treated with exclusive chemoradiation therapy remains unknown. This study evaluated the overall, disease-free and progression-free survival of these patients. METHODS: Overall, disease-free and progression-free survival of 94 patients diagnosed with oropharynx, nasopharynx, and hypopharynx cancer, who participated on a phase III study, was evaluated from 2007 to 2015. The patients were subjected to conventional radiotherapy plus cisplatin every 3weeks. LLLT was applied with an InGaAlP diode (660nm-100mW-1J-4J/cm2). RESULTS: With a median follow-up of 41.3months (range 0.7-101.9), patients receiving LLLT had a statistically significant better complete response to treatment than those in the placebo group (LG=89.1%; PG=67.4%; p=0.013). Patients subjected to LLLT also displayed increase in progression-free survival than those in the placebo group (61.7% vs. 40.4%; p=0.030; HR:1:93; CI 95%: 1.07-3.5) and had a tendency for better overall survival (57.4% vs. 40.4%; p=0.90; HR:1.64; CI 95%: 0.92-2.91). CONCLUSION: This is the first study to suggest that LLLT may improve survival of head and neck cancer patients treated with chemoradiotherapy. Further studies, with a larger sample, are necessary to confirm our findings.


Subject(s)
Chemoradiotherapy , Head and Neck Neoplasms/therapy , Low-Level Light Therapy , Stomatitis/prevention & control , Female , Humans , Male , Middle Aged , Survival Analysis
13.
Hum Psychopharmacol ; 32(3)2017 05.
Article in English | MEDLINE | ID: mdl-28657190

ABSTRACT

OBJECTIVE: "Krokodil" is the street name for an impure homemade drug mixture used as a cheap substitute for heroin, containing desomorphine as the main opioid. Abscesses, gangrene, thrombophlebitis, limb ulceration and amputations, jaw osteonecrosis, skin discoloration, ulcers, skin infections, and bleeding are some of the typical reported signs in humans. This study aimed to understand the toxicity of krokodil using Wistar male rats as experimental model. METHODS: Animals were divided into seven groups and exposed subcutaneously to NaCl 0.9% (control), krokodil mixture free of psychotropic substances (blank krokodil), pharmaceutical grade desomorphine 1 mg/kg, and four different concentrations of krokodil (containing 0.125, 0.25, 0.5, and 1 mg/kg of desomorphine) synthesized accordingly to a "domestic" protocol followed by people who inject krokodil (PWIK). Daily injections for five consecutive days were performed, and animals were sacrificed 24 hr after the last administration. Biochemical and histological analysis were carried out. RESULTS: It was shown that the continuous use of krokodil may cause injury at the injection area, with formation of necrotic zones. The biochemical results evidenced alterations on cardiac and renal biomarkers of toxicity, namely, creatine kinase, creatine kinase-MB, and uric acid. Significant alteration in levels of reduced and oxidized glutathione on kidney and heart suggested that oxidative stress may be involved in krokodil-mediated toxicity. Cardiac congestion was the most relevant finding of continuous krokodil administration. CONCLUSIONS: These findings contribute notably to comprehension of the local and systemic toxicological impact of this complex drug mixture on major organs and will hopefully be useful for the development of appropriate treatment strategies towards the human toxicological effects of krokodil.


Subject(s)
Analgesics, Opioid/toxicity , Codeine/analogs & derivatives , Heart/drug effects , Illicit Drugs/toxicity , Kidney/drug effects , Skin Diseases/chemically induced , Analgesics, Opioid/administration & dosage , Animals , Codeine/administration & dosage , Codeine/toxicity , Humans , Injections, Subcutaneous , Kidney/pathology , Liver/drug effects , Liver/pathology , Lung/drug effects , Lung/pathology , Male , Necrosis/chemically induced , Necrosis/pathology , Organ Size/drug effects , Organ Size/physiology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Rats , Rats, Wistar , Skin Diseases/pathology , Tissue Distribution/drug effects , Tissue Distribution/physiology
14.
Carbohydr Polym ; 153: 212-221, 2016 Nov 20.
Article in English | MEDLINE | ID: mdl-27561489

ABSTRACT

In the present work composite nanoparticles with a magnetic core and a chitosan-based shell were produced as drug delivery systems for doxorubicin (DOX). The results show that composite nanoparticles with a hydrodynamic diameter within the nanometric range are able to encapsulate more DOX than polymeric nanoparticles alone corresponding also to a higher drug release. Moreover the synthesis method of the iron oxide nanoparticles influences the total amount of DOX released and a high content of iron oxide nanoparticles inhibits DOX release. The modelling of the experimental results revealed a release mechanism dominated by Fickian diffusion.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Chitosan/chemistry , Doxorubicin/administration & dosage , Drug Carriers/chemistry , Drug Liberation , Ferric Compounds/chemistry , Metal Nanoparticles/chemistry , Antibiotics, Antineoplastic/chemistry , Diffusion , Doxorubicin/chemistry , Drug Carriers/chemical synthesis , Hydrogen-Ion Concentration , Models, Theoretical , Nanocomposites/chemistry , Particle Size , Theranostic Nanomedicine
15.
Carbohydr Polym ; 149: 382-90, 2016 09 20.
Article in English | MEDLINE | ID: mdl-27261762

ABSTRACT

Chitosan is a biopolymer widely used for biomedical applications such as drug delivery systems, wound healing, and tissue engineering. Chitosan can be used as coating for other types of materials such as iron oxide nanoparticles, improving its biocompatibility while extending its range of applications. In this work iron oxide nanoparticles (Fe3O4 NPs) produced by chemical precipitation and thermal decomposition and coated with chitosan with different molecular weights were studied. Basic characterization on bare and chitosan-Fe3O4 NPs was performed demonstrating that chitosan does not affect the crystallinity, chemical composition, and superparamagnetic properties of the Fe3O4 NPs, and also the incorporation of Fe3O4 NPs into chitosan nanoparticles increases the later hydrodynamic diameter without compromising its physical and chemical properties. The nano-composite was tested for magnetic hyperthermia by applying an alternating current magnetic field to the samples demonstrating that the heating ability of the Fe3O4 NPs was not significantly affected by chitosan.


Subject(s)
Chitosan/chemistry , Magnetic Phenomena , Magnetite Nanoparticles/chemistry , Temperature , Molecular Weight
16.
Carbohydr Polym ; 147: 304-312, 2016 08 20.
Article in English | MEDLINE | ID: mdl-27178936

ABSTRACT

In the present work, two drug delivery systems were produced by encapsulating doxorubicin into chitosan and O-HTCC (ammonium-quaternary derivative of chitosan) nanoparticles. The results show that doxorubicin release is independent of the molecular weight and is higher at acidic pH (4.5) than at physiological pH. NPs with an average hydrodynamic diameter bellow 200nm are able to encapsulate up to 70% and 50% of doxorubicin in the case of chitosan and O-HTCC nanoparticles, respectively. O-HTCC nanoparticles led to a higher amount of doxorubicin released than chitosan nanoparticles, for the same experimental conditions, although the release mechanism was not altered. A burst effect occurs within the first hours of release, reaching a plateau after 24h. Fitting mathematical models to the experimental data led to a concordant release mechanism between most samples, indicating an anomalous or mixed release, which is in agreement with the swelling behavior of chitosan described in the literature.


Subject(s)
Chitosan/chemistry , Doxorubicin/administration & dosage , Drug Carriers/chemistry , Nanoparticles/chemistry , Drug Delivery Systems , Models, Chemical
17.
Oral Oncol ; 52: 85-90, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26559740

ABSTRACT

BACKGROUND: Oral mucositis is a major event increasing treatment costs of head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiation (CRT). This study was designed to estimate the cost-effectiveness of low-level laser therapy (LLLT) to prevent oral mucositis in HNSCC patients receiving CRT. METHODS: From June 2007 to December 2010, 94 patients with HNSCC of nasopharynx, oropharynx, and hypopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial. CRT consisted of conventional radiotherapy (RT: 70.2 Gy, 1.8 Gy/d, 5 times/wk)+concurrent cisplatin (100mg/m2) every 3 weeks. An InGaAlP (660 nm-100 mW-4J/cm2) laser diode was used for LLLT. RESULTS: From the perspective of Brazil's public health care system (SUS), total costs were higher in Placebo Group (PG) than Laser Group (LG) for opioid use (LG=US$ 9.08, PG=US$ 44.28), gastrostomy feeding (LG=US$ 50.50, PG=US$ 129.86), and hospitalization (PG=US$ 77.03). In LG, the cost was higher for laser therapy only (US$ 1880.57). The total incremental cost associated with the use of LLLT was US$ 1689.00 per patient. The incremental cost-effectiveness ratio (ICER) was US$ 4961.37 per grade 3-4 OM case prevented compared to no treatment. CONCLUSIONS: Our results indicate that morbidity was lower in the Laser Group and that LLLT was more cost-effective than placebo up to a threshold of at least US$ 5000 per mucositis case prevented. CLINICAL TRIAL INFORMATION: NCT01439724.


Subject(s)
Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/adverse effects , Cost-Benefit Analysis , Head and Neck Neoplasms/therapy , Low-Level Light Therapy/economics , Mucositis/prevention & control , Aged , Brazil , Carcinoma, Squamous Cell/economics , Chemoradiotherapy/economics , Double-Blind Method , Female , Head and Neck Neoplasms/economics , Humans , Male , Middle Aged , Mucositis/economics , Prospective Studies , Treatment Outcome
18.
Nanotechnology ; 26(42): 425704, 2015 Oct 23.
Article in English | MEDLINE | ID: mdl-26421876

ABSTRACT

Iron oxide nanoparticles (NPs) have been extensively studied in the last few decades for several biomedical applications such as magnetic resonance imaging, magnetic drug delivery and hyperthermia. Hyperthermia is a technique used for cancer treatment which consists in inducing a temperature of about 41-45 °C in cancerous cells through magnetic NPs and an external magnetic field. Chemical precipitation was used to produce iron oxide NPs 9 nm in size coated with oleic acid and trisodium citrate. The influence of both stabilizers on the heating ability and in vitro cytotoxicity of the produced iron oxide NPs was assessed. Physicochemical characterization of the samples confirmed that the used surfactants do not change the particles' average size and that the presence of the surfactants has a strong effect on both the magnetic properties and the heating ability. The heating ability of Fe3O4 NPs shows a proportional increase with the increase of iron concentration, although when coated with trisodium citrate or oleic acid the heating ability decreases. Cytotoxicity assays demonstrated that both pristine and trisodium citrate Fe3O4 samples do not reduce cell viability. However, oleic acid Fe3O4 strongly reduces cell viability, more drastically in the SaOs-2 cell line. The produced iron oxide NPs are suitable for cancer hyperthermia treatment and the use of a surfactant brings great advantages concerning the dispersion of NPs, also allowing better control of the hyperthermia temperature.


Subject(s)
Colloids/chemistry , Magnetite Nanoparticles/chemistry , Surface-Active Agents/chemistry , Animals , Cell Survival/drug effects , Chlorocebus aethiops , Colloids/toxicity , Hot Temperature , Magnetite Nanoparticles/toxicity , Vero Cells
19.
PLoS One ; 10(8): e0134740, 2015.
Article in English | MEDLINE | ID: mdl-26244369

ABSTRACT

Fructose, an everyday component of western diet associated to chronic hyperglycemia and enhanced free radical production, impairs endothelial function and supplementation with antioxidants might improve it. In this study we investigated if vitamin E could reverse the microvascular damage elicited by fructose. Male Syrian golden hamsters drank either 10% fructose solution (F) or filtered water (C), combined with three concentrations of vitamin E in their chows [zero, normal (VE) or 5X (5XVE)] during 60 days. Microvascular reactivity in response to topical application of acetylcholine (Ach; endothelium-dependent vasodilator) or sodium nitroprusside (SNP; endothelium-independent vasodilator) and macromolecular permeability increase induced by either 30 min ischemia followed by reperfusion (I/R) or topical application of histamine (5 µM) were assessed using the cheek pouch preparation. Compared to controls (drinking filtered water), fructose-drinking animals showed decreased vasodilatation to acetylcholine in all concentrations tested (-56.2% for 10-9M, -53.9% for 10-7M and -43.7% for 10-5M). On the other hand, vitamin E supplementation resulted in increased responses for both water and fructose drinking groups (177.4% for F vs. F/5XVE and 241.6% for C vs. C/5XVE for 10-5M Ach). Endothelial-independent vasodilatation explored by topical application of SNP was restored and even enhanced with the supplementation of 5X vitamin E in both groups (80.1% for F vs. F/5XVE; 144.2% for C vs. C/5XVE; 3.4% of difference for C/5XVE vs. F/5XVE on 10-5M SNP). The number of leaky sites after I/R and histamine stimuli in vitamin E supplemented animals decreased (-25.1% and -15.3% for F vs. F/5XVE; and -21.7% and -16% of leaky sites comparing C vs. C/5XVE, respectively for I/R and histamine stimuli) pointing to tightening of the endothelial barrier for macromolecular permeability. Our results strongly suggest that vitamin E could improve the endothelial function and permeability barrier and also reverse impairments elicited by sugar overload.


Subject(s)
Antioxidants/pharmacology , Capillary Permeability/drug effects , Fructose/adverse effects , Microcirculation/drug effects , Sweetening Agents/adverse effects , alpha-Tocopherol/pharmacology , Animals , Antioxidants/administration & dosage , Cricetinae , Male , Vasodilation/drug effects , alpha-Tocopherol/administration & dosage
20.
J Colloid Interface Sci ; 419: 46-51, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-24491328

ABSTRACT

Iron oxide nanoparticles are having been extensively investigated for several biomedical applications such as hyperthermia and magnetic resonance imaging. However, one of the biggest problems of these nanoparticles is their aggregation. Taking this into account, in this study the influence of three different surfactants (oleic acid, sodium citrate and Triton X-100) each one with various concentrations in the colloidal solutions stability was analyzed by using a rapid and facile method, the variation in the optical absorbance along time. The synthesized nanoparticles through chemical precipitation showed an average size of 9 nm and a narrow size distribution. X-ray diffraction pattern and Fourier Transform Infrared analysis confirmed the presence of pure magnetite. SQUID measurements showed superparamagnetic properties with a blocking temperature around 155 K. In addition it was observed that neither sodium citrate nor Triton X-100 influences the magnetic properties of the nanoparticles. On the other hand, oleic acid in a concentration of 64 mM decreases the saturation magnetization from 67 to 45 emu/g. Oleic acid exhibits a good performance as stabilizer of the iron oxide nanoparticles in an aqueous solution for 24h, for concentrations that lead to the formation of the double layer.


Subject(s)
Contrast Media/chemistry , Ferric Compounds/chemistry , Magnetic Fields , Nanoparticles/chemistry , Surface-Active Agents/chemistry , Colloids , Contrast Media/pharmacology , Ferric Compounds/pharmacology , Fever/drug therapy , Magnetic Resonance Imaging/methods , Surface-Active Agents/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...