RESUMO
Combination therapy has been considered one of the most promising approaches for improving the therapeutic effects of anticancer drugs. This is the first study that uses two different antioxidants in full-characterized niosomal formulation and thoroughly evaluates their synergistic effects on breast cancer cells. In this study, in-silico studies of hydrophilic and hydrophobic drugs (ascorbic acid: Asc and curcumin: Cur) interactions and release were investigated and validated by a set of in vitro experiments to reveal the significant improvement in breast cancer therapy using a co-delivery approach by niosomal nanocarrier. The niosomal nanoparticles containing surfactants (Span 60 and Tween 60) and cholesterol at 2:1 M ratio were prepared through the film hydration method. A systematic evaluation of nanoniosomes was carried out. The release profile demonstrated two phases (initial burst followed by sustained release) and a pH-dependent release schedule over 72 h. The optimized niosomal preparation displayed superior storage stability for up to 2 months at 4 °C, exhibiting extremely minor changes in pharmaceutical encapsulation efficiency and size. Free dual drugs (Asc + Cur) and dual-drug loaded niosomes (Niosomal (Asc + Cur)) enhanced the apoptotic activity and cytotoxicity and inhibited cell migration which confirmed the synergistic effect of co-encapsulated drugs. Also, significant up-regulation of p53 and Bax genes was observed in cells treated with Asc + Cur and Niosomal (Asc + Cur), while the anti-apoptotic Bcl-2 gene was down-regulated. These results were in correlation with the increase in the enzyme activity of SOD, CAT, and caspase, and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) upon treatment with the mentioned drugs. Furthermore, these anti-cancer effects were higher when using Niosomal (Asc + Cur) than Asc + Cur. Histopathological examination also revealed that Niosomal (Asc + Cur) had a lower mitosis index, invasion, and pleomorphism than Asc + Cur. These findings indicated that niosomal formulation for co-delivery of Asc and Cur would offer a promising delivery system for an effective breast cancer treatment.
Assuntos
Antineoplásicos , Neoplasias da Mama , Curcumina , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Lipossomos/química , Lipossomos/farmacologia , Lipossomos/uso terapêutico , Curcumina/farmacologia , Curcumina/química , Polissorbatos/química , Polissorbatos/uso terapêuticoRESUMO
OBJECTIVES: To develop alginate nanoparticles functionalized with polysorbate 80 (P80) as miltefosine carriers for brain targeting in the oral treatment of cryptococcal meningitis. METHODS: Miltefosine-loaded alginate nanoparticles functionalized or not with P80 were produced by an emulsification/external gelation method and the physicochemical characteristics were determined. The haemolytic activity and cytotoxic and antifungal effects of nanoparticles were assessed in an in vitro model of the blood-brain barrier (BBB). A murine model of disseminated cryptococcosis was used for testing the efficacy of oral treatment with the nanoparticles. In addition, serum biomarkers were measured for toxicity evaluation and the nanoparticle biodistribution was analysed. RESULTS: P80-functionalized nanoparticles had a mean size of â¼300 nm, a polydispersity index of â¼0.4 and zeta potential around -50 mV, and they promoted a sustained drug release. Both nanoparticles were effective in decreasing the infection process across the BBB model and reduced drug cytotoxicity and haemolysis. In in vivo cryptococcosis, the oral treatment with two doses of P80 nanoparticles reduced the fungal burden in the brain and lungs, while the non-functionalized nanoparticles reduced fungal amount only in the lungs, and the free miltefosine was not effective. In addition, the P80-functionalization improved the nanoparticle distribution in several organs, especially in the brain. Finally, treatment with nanoparticles did not cause any toxicity in animals. CONCLUSIONS: These results support the potential use of P80-functionalized alginate nanoparticles as miltefosine carriers for non-toxic and effective alternative oral treatment, enabling BBB translocation and reduction of fungal infection in the brain.
Assuntos
Criptococose , Meningite Criptocócica , Nanopartículas , Camundongos , Animais , Meningite Criptocócica/tratamento farmacológico , Polissorbatos/uso terapêutico , Alginatos/uso terapêutico , Distribuição Tecidual , Encéfalo , Criptococose/tratamento farmacológico , Portadores de Fármacos/uso terapêuticoRESUMO
Omalizumab can cause hypersensitivity reactions. We herein report the first case of an 18-year-old woman with refractory cough-predominant asthma that correlated with allergic reactions caused by omalizumab and the coronavirus disease 2019 (COVID-19) vaccine. The patient developed angioedema after taking omalizumab. She had previously experienced intense coughing immediately after receiving a COVID-19 vaccine. A skin prick test was positive for polysorbate 20, which was probably the cause of the allergic reactions to omalizumab and the COVID-19 vaccine. Clinicians should check for an allergic reaction, irrespective of its intensity, triggered by polysorbate and be careful when prescribing biologics to patients in order to avoid allergic reactions.
Assuntos
Angioedema , Antialérgicos , Vacinas contra COVID-19 , COVID-19 , Omalizumab , Adolescente , Feminino , Humanos , Angioedema/induzido quimicamente , Antialérgicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Coronavirus , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Omalizumab/efeitos adversos , Polissorbatos/uso terapêuticoRESUMO
The aim of this work was to design innovative nanostructured lipid carriers (NLCs) for the delivery of dexibuprofen (DXI) as an antiproliferative therapy against tumoral processes, and overcome its side effects. DXI-NLC samples were prepared with beeswax, Miglyol 812 and Tween 80 using high-pressure homogenization. A two-level factorial design 24 was applied to optimize the formulation, and physicochemical properties such as particle size, zeta potential, polydispersity index and entrapment efficiency were measured. Optimized parameters of DXI-NLCs exhibited a mean particle size of 152.3 nm, a polydispersity index below 0.2, and high DXI entrapment efficiency (higher than 99%). Moreover, DXI-NLCs provided a prolonged drug release, slower than the free DXI. DXI-NLCs were stable for 2 months and their morphology revealed that they possess a spherical shape. In vitro cytotoxicity and anticancer potential studies were performed towards prostate (PC-3) and breast (MDA-MB-468) cancer cell lines. The highest activity of DXI-NLCs was observed towards breast cancer cells, which were effectively inhibited at 3.4 µM. Therefore, DXI-NLCs constitute a promising antiproliferative therapy that has proven to be especially effective against breast cancer.
Assuntos
Neoplasias da Mama , Nanoestruturas , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Humanos , Ibuprofeno/análogos & derivados , Lipídeos/química , Masculino , Nanoestruturas/química , Tamanho da Partícula , Polissorbatos/uso terapêuticoRESUMO
Chemotherapy is a conventional treatment for glioma, but its efficacy is greatly limited due to low blood-brain barrier (BBB) permeability and lack of specificity. Herein, intelligent and tumor microenvironment (TME)-responsive folic acid (FA) derivatives and mitochondria-targeting berberine (BBR) derivatives co-modified liposome coated with Tween 80 loading paclitaxel (PTX-Tween 80-BBR + FA-Lip) was constructed. Specifically speaking, liposomes modified by FA can be effectively target ed to glioma cells. BBR, due to its delocalized positive electricity and lipophilicity, can be attracted by mitochondrial membrane potential and concentrate on mitochondria to achieve mitochondrial targeting and induce cell apoptosis. By simultaneously modifying the liposome with FA and BBR to deliver drugs, leads to a good therapeutic effect of glioma through FA-based glioma targeting and BBR-based mitochondrial targeting. In addition, the surface of the liposome was coated with Tween 80 to further improve BBB penetration. All results exhibited that PTX-Tween 80-BBR + FA-Lip can observably improve the chemotherapy therapeutic efficacy through the highly specific tumor targeting and mitochondrial targeting, which can provide new ideas and methods for the targeted therapy of glioma.
Assuntos
Berberina , Neoplasias Encefálicas , Glioma , Berberina/farmacologia , Berberina/uso terapêutico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Concentração de Íons de Hidrogênio , Lipossomos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Polissorbatos/uso terapêutico , Microambiente TumoralRESUMO
OBJECTIVE: Acute decompensated heart failure is often treated with a combination of loop and thiazide-like diuretics. Of these thiazide-like diuretics, two common choices are intravenous chlorothiazide or oral metolazone. Metolazone is more potent and has a longer duration of action, but since it is an oral formulation, it has a longer on-set time as compared to chlorothiazide. In addition, metolazone is poorly water-soluble, thereby rendering intravenous formulation more challenging. To address these issues, we proposed the formulation of a solvent-free metolazone emulsion for intravenous administration. METHODS: An oil-in-water emulsion containing 1 mg/mL of metolazone was formulated by homogenizing soybean oil and l-lecithin in water in the presence of optimized concentrations of glycerin with tween 80 or poloxamer 188 as surfactant. The emulsion was characterized on the basis of particle size, zeta potential, morphology and metolazone release kinetics. The diuretic effect of the metolazone emulsion was evaluated in rats. RESULTS: The 1 mg/mL metolazone emulsion prepared with 5% tween 80 displayed the best physical stability. The emulsion exhibited a hydrodynamic diameter of 157.13±1.52 nm. About 93% of metolazone was released from the formulation within 2 h. The 2 mg/kg and 4 mg/kg dose of the metolazone emulsion increased urine output in the rats by 68.9 and 134%, respectively, as compared to control rats. Furthermore, the 4 mg/kg dose exhibited a 168.8%, 25.8%, and 150.9% increase in sodium, potassium, and chloride, respectively. CONCLUSION: This metolazone emulsion was capable of increasing urine volume output and demonstrated both natriuretic and kaliuretic properties.
Assuntos
Insuficiência Cardíaca , Metolazona , Administração Intravenosa , Animais , Clorotiazida/uso terapêutico , Diuréticos/farmacologia , Diuréticos/uso terapêutico , Emulsões , Insuficiência Cardíaca/tratamento farmacológico , Metolazona/farmacologia , Metolazona/uso terapêutico , Polissorbatos/uso terapêutico , Ratos , ÁguaRESUMO
OBJECTIVES: Dalbavancin is a lipoglycopeptide with a long half-life, making it a promising treatment for infections requiring prolonged therapy, such as complicated Staphylococcus aureus bacteraemia. Free drug concentration is a critical consideration with prolonged treatment, since free concentration-time profiles may best correlate with therapeutic effect. In support of future clinical trials, we aimed to develop a reliable and reproducible assay for measuring free dalbavancin concentrations. METHODS: The ultracentrifugation technique was used to determine free dalbavancin concentrations in plasma at two concentrations (50 and 200â mg/L) in duplicate. Centrifuge tubes and pipette tips were treated for 24â h before use with Tween 80 to assess adsorption. Dalbavancin concentrations were analysed from the plasma samples (total) and middle layer samples (free) by LC/MS/MS with isotopically labelled internal standard. Warfarin served as a positive control with known high protein binding. RESULTS: Measurement of free dalbavancin was sensitive to adsorption onto plastic. Treatment of tubes and pipette tips with ≥2% Tween 80 effectively prevented drug loss during protein binding experiments. By the ultracentrifugation method, dalbavancin's protein binding was estimated to be approximately 99%. CONCLUSIONS: Dalbavancin has very high protein binding. Given dalbavancin's high protein binding, accurate measurement of free dalbavancin concentrations should be a key consideration in future exposure-response studies, especially clinical trials. Future investigations should confirm if the active fraction is best predicted by the free or total fraction.
Assuntos
Bacteriemia , Infecções Estafilocócicas , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Polissorbatos/uso terapêutico , Ligação Proteica , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Espectrometria de Massas em Tandem , Teicoplanina/análogos & derivados , Teicoplanina/uso terapêuticoRESUMO
It is generally recognized that dysregulation of the immune system plays a critical role in many diseases, including autoimmune diseases and cancer. T cells play a crucial role in maintaining self-tolerance, while loss of immune tolerance and T cell activation can lead to severe inflammation and tissue damage. T cell responses have a key role in the effectiveness of vaccination strategies and immunomodulating therapies. Immunomonitoring methods have the ability to elucidate immunological processes, monitor the development of disease and assess therapeutic effects. In this respect, it is of particular interest to evaluate antigen (Ag)-specific T cells by determining their frequency, type and functionality in cellular assays. Nevertheless, Ag-specific T cells are detected infrequently in most diseases using current techniques. Many efforts have been made to develop more sensitive, reproducible, and reliable methods for Ag-specific T cell detection. It has been found that analysis of cellular proliferation can be a useful tool to determine the presence and frequency of Ag-specific T cell and to provides insight into modulation of the T cell response by a specific antigen or therapy. However, the selection of a cut-off value for a positive response and therefore a more accurate interpretation of the data, continues to be a major concern. Here, we provide guidelines to select a proper cut-off for monitoring of Ag-specific CD4+ T cell responses. In vitro Ag-stimulation has been assessed with two methods; a dye-based proliferation assay and 3H-thymidine-based assay. Two cut-off approaches are compared; mean and variance of control wells, and the stimulation index. By evaluating the proliferative response to the in vitro Ag-stimulation using these two methods, we demonstrate the importance of taking into consideration the variability of the control wells to distinguish a positive from a false positive response.
Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Citometria de Fluxo , Corantes Fluorescentes , Fatores Imunológicos/uso terapêutico , Vacinas contra Influenza/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Timidina/metabolismo , Trítio , Adjuvantes Imunológicos/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/imunologia , Polissorbatos/uso terapêutico , Cintilografia , Reprodutibilidade dos Testes , Esqualeno/uso terapêuticoAssuntos
Alérgenos/imunologia , Anafilaxia/diagnóstico , Asma/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Hipersensibilidade/diagnóstico , Polissorbatos/efeitos adversos , Adulto , Alérgenos/uso terapêutico , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/complicações , Feminino , Humanos , Omalizumab/efeitos adversos , Omalizumab/uso terapêutico , Polissorbatos/uso terapêuticoRESUMO
Due to the complexity and fragility of biological drug products, several challenges exist in their formulation development. Excipients are added to increase product stability, maintain tonicity, and facilitate drug delivery. The potential implications of these additive substances merit clinical consideration. We assessed the safety risk of excipients on the basis of their type and variability through an assessment framework, which quantifies excipient complexity in 230 biological formulations, and identifies excipient-related adverse events through published case reports. A biologic on average contained 4.45 excipients, half of that found in oral medications. The frequency distribution was heavily skewed towards the most commonly occurring excipients: water (40.4%), sodium chloride (38.3%), polysorbate 80 (28.7%), sucrose (24.4%), and mannitol (20.9%), with 44.4% of formulations not listing the concentration of the most commonly occurring inactive ingredients. A literature search revealed only 17 case reports of excipient-related adverse events, suggesting the need for more clarity for clinicians on the safety of chemical additives. These cases included injection site reactions, anaphylaxis, hyperglycemia, and acute renal failure. With the expansion of the biopharmaceutical market, it is important to consider the safety data of biologic excipients, so that therapy can be tailored appropriately for a specific patient.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Anafilaxia/induzido quimicamente , Excipientes/efeitos adversos , Hiperglicemia/induzido quimicamente , Química Farmacêutica , Excipientes/uso terapêutico , Humanos , Manitol/efeitos adversos , Manitol/uso terapêutico , Polissorbatos/efeitos adversos , Polissorbatos/uso terapêutico , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/uso terapêutico , Sacarose/efeitos adversos , Sacarose/uso terapêutico , Água/efeitos adversosRESUMO
Polysorbate 80, a sorbitan derivate, is a surfactant used as an emulsifier in some foods in concentrations of up to 0.5%. It was recently shown in vitro that polysorbate 80 decreases the minimum bactericidal concentrations of clarithromycin and metronidazole and may also revert antibiotic resistance. We report the case of an adult man, suffering from symptomatic Helicobacter pylori (HP) infection resistant to two courses of treatment with PPI plus amoxicillin and clarithromycin, and PPI plus clarithromycin and metronidazole. He was treated with a further antibiotic approach consisting of two-week administration of clarithromycin, metronidazole, PPI and polysorbate 80 as an add on therapy. Eradication of infection was confirmed by 13C-urea breath test two and five months after completion of the treatment course. Complete regression of symptoms was also achieved. To our knowledge, this is the first case of HP infection eradicated with a combination therapy based on polysorbate 80 added to antibiotics.
Assuntos
Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Polissorbatos/uso terapêutico , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Combinação de Medicamentos , Humanos , Masculino , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Polissorbatos/administração & dosagemRESUMO
AIM: Fosaprepitant, an intravenous neurokinin-1 receptor antagonist for chemotherapy-induced nausea and vomiting, contains polysorbate 80, which is associated with infusion-site adverse events (ISAEs) and hypersensitivity systemic reactions (HSRs). This study investigated ISAEs/HSRs following fosaprepitant with anthracycline-containing chemotherapy. PATIENTS & METHODS: This retrospective chart review noted ISAEs/HSRs following the anthracycline doxorubicin+cyclophosphamide and a three-drug fosaprepitant regimen, via peripheral line. RESULTS: 35/127 patients (28%) developed ISAEs/HSRs with chemotherapy and antiemetic therapy: 32 developed 137 individual ISAEs, primarily erythema, pain and catheter-site swelling; 16 developed 50 individual HSRs, primarily edema/swelling, erythema or dermatitis (no anaphylaxis). CONCLUSION: Fosaprepitant is associated with a significant ISAE/HSR rate following anthracycline-containing chemotherapy via peripheral line. Polysorbate 80-free intravenous neurokinin-1 receptor antagonist may provide a safer chemotherapy-induced nausea and vomiting prophylaxis option.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Morfolinas/efeitos adversos , Náusea/fisiopatologia , Antagonistas dos Receptores de Neurocinina-1/efeitos adversos , Vômito/fisiopatologia , Administração Intravenosa , Adulto , Idoso , Antraciclinas/efeitos adversos , Antraciclinas/uso terapêutico , Antieméticos/efeitos adversos , Antieméticos/uso terapêutico , Aprepitanto/efeitos adversos , Aprepitanto/uso terapêutico , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/uso terapêutico , Náusea/induzido quimicamente , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Polissorbatos/efeitos adversos , Polissorbatos/uso terapêutico , Vômito/induzido quimicamenteRESUMO
Polysorbate 80 is a synthetic nonionic surfactant used as an excipient in drug formulation. Various products formulated with polysorbate 80 are used in the oncology setting for chemotherapy, supportive care, or prevention, including docetaxel, epoetin/darbepoetin, and fosaprepitant. However, polysorbate 80, like some other surfactants, is not an inert compound and has been implicated in a number of systemic and injection- and infusion-site adverse events (ISAEs). The current formulation of intravenous fosaprepitant has been associated with an increased risk of hypersensitivity systemic reactions (HSRs). Factors that have been associated with an increased risk of fosaprepitant-related ISAEs include the site of administration (peripheral vs. central venous), coadministration of anthracycline-based chemotherapy, number of chemotherapy cycles or fosaprepitant doses, and concentration of fosaprepitant administered. Recently, two polysorbate 80-free agents have been approved: intravenous rolapitant, which is a neurokinin 1 (NK-1) receptor antagonist formulated with the synthetic surfactant polyoxyl 15 hydroxystearate, and intravenous HTX-019, which is a novel NK-1 receptor antagonist free of synthetic surfactants. Alternative formulations will obviate the polysorbate 80-associated ISAEs and HSRs and should improve overall management of chemotherapy-induced nausea and vomiting.Funding Heron Therapeutics, Inc.
Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Polissorbatos/uso terapêutico , Vômito/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Vômito/etiologiaRESUMO
The aim of the present study was to compare the efficacy of chitosan and MTAD for the smear layer removal from the root canal through a scanning electron microscope (SEM). Thirty teeth were randomly divided into three groups according to the final irrigants: 0.2% chitosan, MTAD, saline (control group). After the mechanical preparation, the samples were irrigated with saline (control group), 0.2% chitosan and MTDA respectively. Then, the samples were split and the smear layer at the apical, middle, and coronal thirds of each root canal was imaged using SEM. The statistical analysis was performed using the Kruskal-Wallis test and the Mann-Whitney U test (α = 5%). The difference between chitosan and MTDA was statistically significant in the apical region (p < 0.05), no significant difference was obtained in the coronal and middle regions in these two experiment groups (p > 0.05). The control group exhibited the lowest efficacy in smear layer removal in all regions. Thus, from the result of the present study, we may conclude that chitosan was more effective in smear layer removal than MTAD especially in the apical third. CONTEXT: Irrigation, which serves a variety of purposes including antibacterial action, tissue dissolution, cleaning and chelating, plays a centric role in the final success of root canal treatment. Thus, more and more attention has been put on the improvement and development of various irrigation techniques or systems. AIMS: The aim of the present study was to compare the efficacy of chitosan and MTAD for the smear layer removal from the root canal through scanning electron microscopy (SEM). SETTINGS AND DESIGN: Thirty single-canal premolars were instrumented with rotary-files and then, randomly assigned to test groups which were irrigated with chitosan and MTDA, and control group was treated with saline. Thereafter, the efficacy of smear layer removal was evaluated by SEM. MATERIALS AND METHODS: Thirty teeth were randomly divided into three groups according to the final irrigants: 0.2% chitosan, MTAD, saline (control group). After the mechanical preparation, the samples were irrigated with saline (control group), 0.2% chitosan and MTDA respectively. Then, the samples were split and the smear layer at the apical, middle, and coronal thirds of each root canal was imaged using SEM. STATISTICAL ANALYSIS USED: Kruskal-Walli test and Mann-Whitney U test Results: The difference between chitosan and MTDA was statistically significant in the apical regions (p < 0.05), no significant difference was obtained in the coronal and middle regions in these two experiment groups (p > 0.05). The control group exhibited the lowest efficacy in smear layer removal in all regions. CONCLUSION: Thus, from the result of present study, we may conclude that chitosan was more effective in smear layer removal than MTAD, especially in the apical third.
Assuntos
Quitosana/uso terapêutico , Ácido Cítrico/uso terapêutico , Doxiciclina/uso terapêutico , Polissorbatos/uso terapêutico , Camada de Esfregaço/tratamento farmacológico , Dente Pré-Molar , Humanos , Microscopia Eletrônica de Varredura , Distribuição Aleatória , Irrigantes do Canal Radicular/uso terapêutico , Preparo de Canal Radicular/métodos , Tratamento do Canal Radicular , Camada de Esfregaço/diagnóstico por imagemRESUMO
OBJECTIVE: Influenza is an important health problem due to the mortality it can cause directly or indirectly as well as the complications and the economic and social costs it produces. Influenza epidemics are being addressed through vaccination campaigns aimed at preventing cases and complications, and the vaccine is officially recommended, as in the case of Spain, for certain risk groups, such as older people, chronic diseases and institutionalized population. The adjuvanted influenza vaccine with MF59, indicated for population over 65 years, has been shown to be more immunogenic than conventional influenza vaccines. The objective of this study is to assess the impact on the national and regional budget of the seasonal vaccination campaigns carried out in Spain using the MF59 adjuvanted vaccine compared to a conventional vaccine in a population older than 65 years. METHODS: We analyzed the budgetary impact of the use of the MF59-adjuvanted vaccine in the national territory and by Autonomous Communities through a modeling of two alternatives, conventional vaccination versus adjuvant vaccination with MF59 in a population older than 65 years. The cases of avoided influenza, avoided complications and avoided costs, as well as the economic impact of the vaccination program have been calculated. RESULTS: With the available information, the budgetary impact of using the influenza vaccine with MF59 in all the over 65 years, amounts to 6,967,288.10 , avoiding for the national set a cost of 89.5 million Euros, which represents a potential savings of 82 million Euros and a cost-benefit ratio of 12.83. CONCLUSIONS: The use of the influenza vaccine with the MF59 adjuvant to all those over 65 years would mean an increase in the efficiency of the vaccination programs currently proposed in all the Autonomous Communities and in the Spanish state.
Assuntos
Vacinas contra Influenza/economia , Vacinas contra Influenza/uso terapêutico , Influenza Humana/economia , Influenza Humana/prevenção & controle , Polissorbatos/economia , Polissorbatos/uso terapêutico , Esqualeno/economia , Esqualeno/uso terapêutico , Vacinação/economia , Adjuvantes Imunológicos , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Feminino , Nível de Saúde , Humanos , Masculino , Espanha/epidemiologiaRESUMO
Nanoemulsions are feasible delivery systems of lipophilic compounds, showing potential as edible coatings with enhanced functional properties. The aim of this work was to study the effect of emulsifier type (stearic acid (SA), Tween 80 (T80) or Tween 80/Span 60 (T80/S60)) and emulsification process (homogenization, ultrasound or microfluidization) on nanoemulsion formation based on oxidized corn starch, beeswax (BW) and natural antimicrobials (lauric arginate and natamycin). The response variables were physicochemical properties, rheological behavior, wettability and antimicrobial activity of BW-starch nanoemulsions (BW-SN). The BW-SN emulsified using T80 and microfluidized showed the lowest droplet size (77.6 ± 6.2 nm), a polydispersion index of 0.4 ± 0.0 and whiteness index (WI) of 31.8 ± 0.8. This BW-SN exhibited a more negative ζ-potential: -36 ± 4 mV, and Newtonian flow behavior, indicating great stability. BW-SN antimicrobial activity was not affected by microfluidization nor the presence of T80, showing inhibition of the deteriorative fungi R. stolonifer, C. gloeosporioides and B. cinerea, and the pathogenic bacterium S. Saintpaul. In addition, regardless of emulsifier type and emulsification process, BW-SN applied on the tomato surface exhibited low contact angles (38.5° to 48.6°), resulting in efficient wettability (-7.0 mN/m to -8.9 mN/m). These nanoemulsions may be useful to produce edible coatings to preserve fresh-produce quality and safety.
Assuntos
Anti-Infecciosos/uso terapêutico , Sistemas de Liberação de Medicamentos , Nanocompostos/química , Ceras/química , Anti-Infecciosos/química , Emulsões/química , Emulsões/uso terapêutico , Hexoses/química , Hexoses/uso terapêutico , Humanos , Nanocompostos/uso terapêutico , Polissorbatos/química , Polissorbatos/uso terapêutico , Amido/química , Amido/uso terapêutico , Ácidos Esteáricos/química , Ácidos Esteáricos/uso terapêuticoRESUMO
Traumatic brain injury (TBI) is the leading cause of death and disability in children and young adults, yet there are currently no treatments available that prevent the secondary spread of damage beyond the initial insult. The chronic progression of this secondary injury is in part caused by the release of reactive oxygen species (ROS) into surrounding normal brain. Thus, treatments that can enter the brain and reduce the spread of ROS should improve outcome from TBI. Here a highly versatile, reproducible, and scalable method to synthesize core-cross-linked nanoparticles (NPs) from polysorbate 80 (PS80) using a combination of thiol-ene and thiol-Michael chemistry is described. The resultant NPs consist of a ROS-reactive thioether cross-linked core stabilized in aqueous solution by hydroxy-functional oligoethylene oxide segments. These NPs show narrow molecular weight distributions and have a high proportion of thioether units that reduce local levels of ROS. In a controlled cortical impact mouse model of TBI, the NPs are able to rapidly accumulate and be retained in damaged brain as visualized through fluorescence imaging, reduce neuroinflammation and the secondary spread of injury as determined through magnetic resonance imaging and histopathology, and improve functional outcome as determined through behavioral analyses. Our findings provide strong evidence that these NPs may, upon further development and testing, provide a useful strategy to help improve the outcome of patients following a TBI.
Assuntos
Antioxidantes/uso terapêutico , Lesões Encefálicas Traumáticas/terapia , Nanopartículas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Sulfetos/uso terapêutico , Animais , Antioxidantes/química , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Modelos Animais de Doenças , Inflamação/metabolismo , Inflamação/patologia , Inflamação/terapia , Camundongos , Camundongos Endogâmicos C57BL , Nanomedicina/métodos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Polissorbatos/química , Polissorbatos/uso terapêutico , Células RAW 264.7 , Sulfetos/químicaRESUMO
Development of self-nanoemulsifying drug delivery systems (SNEDDS) of polypeptide-k (PPK) is reported with the aim to achieve its oral delivery. Box-Behnken design (BBD) was adopted to develop and optimize the composition of SNEDDS. Oleoyl polyoxyl-6 glycerides (A), Tween 80 (B), and diethylene glycol monoethyl ether (C) were used as oil, surfactant and co-surfactant, respectively as independent variables. The effect of variation in their composition was observed on the mean droplet size (y1), polydispersity index (PDI) (y2), % drug loading (y3) and zeta potential (y4). As per the optimal design, seventeen SNEDDS prototypes were prepared. The optimized composition of SNEDDS formulation was 25% v/v Oleoyl polyoxyl-6 glycerides, 37% v/v Tween 80, 38% v/v diethylene glycol monoethyl ether, and 3% w/v PPK. The optimized formulation revealed values of y1, y2, y3, and y4 as 31.89nm, 0.16, 73.15%, and -15.65mV, respectively. Further the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, disintegration and dissolution properties. Both, liquid and solid-SNEDDS have shown release of >90% within 10min. The formulation was found stable with change in pH, dilution, temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline PPK was observed in amorphous state in solid SNEDDS when characterized through DSC and PXRD studies. The biochemical, hematological and histopathological results of streptozotocin induced diabetic rats shown promising antidiabetic potential of PPK loaded in SNEDDS at its both the doses (i.e. 400mg/kg and 800mg/kg) as compared to its naïve form at both the doses. The study revealed successful formulation of SNEDDS for oral delivery of PPK.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Nanoestruturas/administração & dosagem , Peptídeos/administração & dosagem , Administração Oral , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Química Farmacêutica , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Emulsões , Etilenoglicóis/administração & dosagem , Etilenoglicóis/química , Etilenoglicóis/uso terapêutico , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Peptídeos/química , Peptídeos/uso terapêutico , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico , Polissorbatos/administração & dosagem , Polissorbatos/química , Polissorbatos/uso terapêutico , Ratos Wistar , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
AIM: To develop NB-201, a nanoemulsion compound, as a novel microbicidal agent against methicillin-resistant Staphylococcus aureus (MRSA) infection, which is a common threat to public health but with limited therapeutic options. MATERIALS & METHODS: NB-201 was tested in in vitro and in vivo murine and porcine models infected with MRSA. RESULTS: Topical treatment of MRSA-infected wounds with NB-201 significantly decreased bacterial load and had no toxic effects on healthy skin tissues. NB-201 attenuated neutrophil sequestration in MRSA-infected wounds and inhibited epidermal and deep dermal inflammation. The levels of proinflammatory cytokines were reduced in NB-201-treated MRSA-infected wounds. CONCLUSION: NB-201 can greatly reduce inflammation characteristic of infected wounds and has antimicrobial activity that effectively kills MRSA regardless of the genetic basis of antibiotic resistance.
Assuntos
Antibacterianos/uso terapêutico , Compostos de Benzalcônio/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Polissorbatos/uso terapêutico , Óleo de Soja/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Compostos de Benzalcônio/farmacologia , Citocinas/análise , Combinação de Medicamentos , Feminino , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Polissorbatos/farmacologia , Óleo de Soja/farmacologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Suínos , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologiaRESUMO
The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29±3.36nm) with very high encapsulation efficiency (74.51±1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems was maintained for 48h as compared to 8h antipsychotic action of pure Olanzapine solution. The weight gain studies for 28days demonstrated a significant inhibition in weight gain for Olanzapine-loaded nanoparticulate systems as compared to the pure Olanzapine. The present research findings indicate that OLN-loaded nanoparticulate systems may be highly promising for effective delivery of Olanzapine with better efficacy and minimum adverse effects.