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The aim of this research was to develop and characterize the chemical and cellular-viability properties of an experimental high-concentration bleaching gel (35 wt%-H2O2) containing calcium-polyphosphate particles (CaPP) at two concentrations (0.5 wt% and 1.5 wt%). The CaPP submicroparticles were synthesized by coprecipitation, keeping a Ca:P ratio of 2:1. The CaPP morphology, size, and chemical and crystal profiles were characterized through scanning and transmission electron microscopy, energy-dispersive X-ray analysis, and X-ray diffraction, respectively. The assessed bleaching gels were experimental (without CaPP); 0.5% CaPP; 1.5% CaPP; and commercial. The gels' pH values and H2O2 concentrations (iodometric titration) were determined. The odontoblast-like cell viability after a gel's exposure was assessed by the MTT assay. The pH and H2O2 concentration were compared through a repeated-measures analysis of variance (ANOVA) and a Tukey's test and the cell viability through a one-way ANOVA and a Tukey's test using a GraphPad Prism (α < 0.05). The CaPP particles were spherical (with Ca and P, 135.7 ± 80.95 nm size) and amorphous. The H2O2 concentration decreased in all groups after mixing (p < 0.001). The 0.5% CaPP resulted in more-stable pH levels and higher viability levels than the experimental one (p < 0.05). The successful incorporation of CaPP had a positive impact on the bleaching gel's chemical and cellular-viability properties when compared to the experimental gel without these particles.
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Alternative methods to the use of animals in research have been a global trend, mainly after the publication of the 3R's principle (Replacement, Reduction, and Refinement), proposed by Russel and Burch. In the cosmetic sector, safety and efficacy assessments using animals have generated controversial debates. For this reason, in vitro research techniques are widely used to assess acute toxicity; corrosivity and irritation; skin sensitization; dermal and percutaneous absorption; repeated dose toxicity; reproductive toxicity; mutagenicity and genotoxicity; carcinogenicity; toxicokinetic studies; photo-induced toxicity; and human data. Although there are many methodologies described, validated, and widely used in the cosmetic area, the evaluation of the safety of cosmetic ingredients and products is still an expanding field. It needs global collaboration among regulatory agencies, universities, and industry, to meet several unmet needs in the fields of sensitization, carcinogenicity, systemic action, among other issues involving safety of users of cosmetic products. This review article will cover the currently most relevant in vitro models regarding irritation, corrosion, sensitization, mutagenicity, genotoxicity, and phototoxicity, to help to choose the most appropriate test for evaluating the safety and toxicity of cosmetic ingredients and products.
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Cosméticos , Animais , Cosméticos/toxicidade , Humanos , PeleRESUMO
Objective: This study evaluated in vitro, the effects of carbamide peroxide 10% (CP) associated with Carbopol® (CP-ct) and Aristoflex® (CP-at) thickeners on human gingival fibroblasts (HGF) cytotoxicity and assessed in situ their effects on dental enamel. Material and methods: The cytotoxicity was analyzed using MTT - Vybrant® proliferation test. For in situ stage, 144 bovine enamel/dentin blocks were randomized into seven groups (n=12). Samples were stained, fixed in intraoral palatal devices and bleached for 4 h, during 14 days, with: Carbopol thickener (ct), Aristoflex thickener (at), CP-ct, CP-at, CP without thickener (CP-wot), Commercial CP (CP-com). The samples had their microhardness (SMH), roughness (Ra) and color analyzed using a microdurometer, a rugosimeter and a spectrophotometer, respectively. The analyses were performed at baseline and 24-h after completion of tooth bleaching. Results: Different thickeners were similar regarding their cytotoxicity. The experimental gels with Carbopol exhibited lower SMH values, while the groups treated with CP exhibited higher Ra values. For the color change results, the groups treated with CP had values above the acceptability and perceptibility limits. Conclusion: CP-at was able to promote an effective bleaching with less alterations of the tooth surface compared to the CP-ct. Hence, Aristoflex stands as a promising thickener in conjunction with CP in order to preserve the physical properties of dental enamel after home bleaching.
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ABSTRACT Alternative methods to the use of animals in research have been a global trend, mainly after the publication of the 3R's principle (Replacement, Reduction, and Refinement), proposed by Russel and Burch. In the cosmetic sector, safety and efficacy assessments using animals have generated controversial debates. For this reason, in vitro research techniques are widely used to assess acute toxicity; corrosivity and irritation; skin sensitization; dermal and percutaneous absorption; repeated dose toxicity; reproductive toxicity; mutagenicity and genotoxicity; carcinogenicity; toxicokinetic studies; photo-induced toxicity; and human data. Although there are many methodologies described, validated, and widely used in the cosmetic area, the evaluation of the safety of cosmetic ingredients and products is still an expanding field. It needs global collaboration among regulatory agencies, universities, and industry, to meet several unmet needs in the fields of sensitization, carcinogenicity, systemic action, among other issues involving safety of users of cosmetic products. This review article will cover the currently most relevant in vitro models regarding irritation, corrosion, sensitization, mutagenicity, genotoxicity, and phototoxicity, to help to choose the most appropriate test for evaluating the safety and toxicity of cosmetic ingredients and products.
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Humanos , Animais , Cosméticos/toxicidade , PeleRESUMO
Wound healing materials to prevent blood loss are crucial during emergency medical treatment because uncontrolled bleeding can lead to patient death. Herein, bioabsorbable fibrous architectures of thrombin-loaded poly(ethylene oxide)-PEO/thrombin-are conceptualized and accomplished via electrospinning for faster wound clotting. Membranes with average fiber diameters ranging from 188 to 264 nm are achieved, where the active thrombin is entrapped within the nanofibers. The results of in vitro and in vivo wound healing activity tests revealed that when the nanofibers with thrombin-loaded capacity are in contact with the wound, the presence of water in the skin or blood catalyzes the degradation of the membranes, thus releasing thrombin. Thrombin then accelerates the wound clotting process. In contrast to other hemostatic materials, PEO/thrombin nanofibers do not require mechanical removal after application, and the viscoelastic nature of such biomaterials enables their conformation to a variety of wound topographies. Remarkably, PEO/thrombin membranes are promising functional materials and their use is a powerful strategy for hemostatic treatment, ranging from simple first aid and sealing to a wound to small surgical procedures.
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Quitosana , Hemostáticos , Nanofibras , Óxido de Etileno , Hemostáticos/farmacologia , Humanos , Polietilenoglicóis , TrombinaRESUMO
Articaine (ATC) is one of the most widely used local anesthetics in dentistry. Despite its safety, local toxicity has been reported. This study aimed to develop an ATC-2- hydroxypropyl-ß-cyclodextrin inclusion complex (ATC HPßCD) and to assess its toxicity in vitro. The inclusion complex was performed by solubilization, followed by a fluorimetric and job plot assay to determine the complex stoichiometry. Scanning electron microscopy, DOSY- 1 H-NMR, differential scanning calorimetry (DSC), and sustained release kinetics were used to confirm the inclusion complex formation. In vitro cytotoxicity was analyzed by MTT assay and immunofluorescence in HGF cells. Fluorimetric and job plot assay determined the inclusion complex stoichiometry (ATC:HPßCD = 1:1) and complex formation time (400 min), as indicated by a strong host/guest interaction (Ka = 117.8 M - 1), complexed fraction (f = 41.4%), and different ATC and ATC HPßCD melting points (172 °C e 235 °C, respectively). The mean of cell viability was 31.87% and 63.17% for 20-mM ATC and 20-mM ATC HPßCD, respectively. Moreover, remarkable cell toxicity was observed with free ATC by immunofluorescence. These results indicate the ATC HPßCD complex could be used to improve the safety of ATC. Further research are needed to establish the anesthetic safety and effectiveness in vivo .
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2-Hidroxipropil-beta-Ciclodextrina/química , Anestésicos Locais/administração & dosagem , Carticaína/administração & dosagem , Gengiva/efeitos dos fármacos , Anestésicos Locais/química , Anestésicos Locais/toxicidade , Carticaína/química , Carticaína/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Imunofluorescência , Gengiva/citologia , Humanos , Testes de Toxicidade , Temperatura de TransiçãoRESUMO
BACKGROUND: Antiproliferative and cytotoxic effects of lidocaine have been reported in tumor cells. However, the use of these drugs is restricted due to their short action with rapid dispersion from the injected site. The complexation of local anesthetics in 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) is able to improve pharmacological features. OBJECTIVE: This study evaluated the antitumor effects of lidocaine and the complex HP-ß-CD-lidocaine (HP-ß-CD-lido). METHODS: In vitro;, human adenocarcinoma (HeLa) and keratinocytes (HaCaT) were exposed to lidocaine formulations and cell viability, proliferation and apoptosis induction were measured. In vivo;, Walker 256 carcinoma cells were subcutaneously injected into the plantar region of the rat right hind paw. The animals were treated with a local application of 5% lidocaine or 5% HP-ß-CD-lido. Doxorubicin (3 mg/Kg/day, intraperitoneal) was used as a positive control. Edema sizes were measured daily and the release of cytokines (TNF-α, IL-1α and CXCL-1) and prostaglandin E2 was evaluated. Histological analysis was also performed. RESULTS: HaCaT IG50 values were 846 µM and 2253 µM for lido and HP-ß-CD-lido, respectively. In HeLa cells, the IG50 was 1765 µM for lido and 2044 µM for HP-ß-CD-lido. Lidocaine formulations significantly reduced the paw edema on day 6 after Walker 256 cells inoculation. However, there were no differences in the release of inflammatory mediators in comparison to the control group. CONCLUSION: Lidocaine formulations were able to reduce the edema in vivo;, without affecting the tumor- induced inflammatory response. The antiproliferative effects of lidocaine formulations may have contributed to tumor reduction.
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2-Hidroxipropil-beta-Ciclodextrina/química , Portadores de Fármacos/química , Edema/tratamento farmacológico , Lidocaína/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Quimiocina CXCL1/metabolismo , Modelos Animais de Doenças , Composição de Medicamentos/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Edema/diagnóstico , Edema/imunologia , Edema/patologia , Células HaCaT , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Interleucina-1alfa/metabolismo , Lidocaína/farmacocinética , Masculino , Neoplasias/complicações , Neoplasias/imunologia , Neoplasias/patologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: To evaluate the effects of 10% carbamide peroxide (CP) with two different thickeners, carbopol (CPc) and natrosol (CPn), on color variation (CV), tooth sensitivity (TS), and cytotoxicity (CC). METHODS: Seventy subjects were distributed into the CPc or CPn groups (n = 35), in a parallel group, randomized, controlled, single-blind clinical trial. Bleaching gels were used by volunteers for 4 h daily for 2 weeks. Color evaluation was performed using a reflectance spectrophotometer, before bleaching treatment (BT), immediately after the first and second weeks of BT, and 1 week and 1 month after BT ended. TS was evaluated using two pain scales, before, during, and after BT. CC was evaluated using MTT after exposure of MDPC-23 cells to the bleaching gels for 4 h. Epoxy replicas of the subjects teeth were made before and after BT and analyzed using a scanning electronic microscope. The data was analyzed using statistical methods. RESULTS: CV and TS showed similar variation between both bleaching gels (p ≤ 0.05). None of the protocols affected cellular metabolism or the surface morphology of enamel. CONCLUSIONS: Bleaching gels with carbopol and natrosol as thickening agents produced similarly effective tooth bleaching and TS, but did not cause cytotoxicity. CLINICAL RELEVANCE: Natrosol could be an alternative as a thickener used in bleaching gels due to its similar bleaching effect and TS when compared with Carbopol.
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Resinas Acrílicas/química , Peróxido de Carbamida/química , Sensibilidade da Dentina , Clareadores Dentários/química , Clareamento Dental , Animais , Linhagem Celular , Cor , Feminino , Géis , Humanos , Masculino , Camundongos , Peróxidos , Método Simples-Cego , Adulto JovemRESUMO
OBJECTIVES: Modified drug delivery systems have been developed to improve pharmacological properties of local anaesthetics. However, the inflammatory potential of these formulations was not investigated. This study compared the in-vitro effects of ropivacaine (ropi) in plain, liposomal (MLV) or 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) formulations on cell viability, apoptosis and cytokine (IL-1α, TNF-α, IL-6 and IL-10) release. METHODS: Human immortalized keratinocytes (HaCaT) and human immortalized gingival fibroblasts (HGF) were exposed to 1-100 µm ropi concentrations. The cell viability was measured by XTT and LIVE/DEAD assay. Apoptosis was performed by flow cytometry, and cytokine release was measured by ELISA assay. KEY FINDINGS: Human immortalized keratinocyte viability was reduced by ropi and both drug delivery systems. However, none of the formulations induced apoptosis. Results showed a differential regulation of IL-1α TNF-α, IL-6 and IL-10 by HaCaT and HGF. Ropi-HP-ß-CD increased twofold the IL-6 release by HGF in comparison with the control, while 100 µm ropi-MLV led to an increased release of all pro-inflammatory cytokines by HGF. CONCLUSION: The loss in cell viability was not related to cellular apoptosis. Ropi complexed with HP-ß-CD showed a similar cytokine release pattern when compared to the plain formulation. Thus, the HP-ß-CD form was a better drug carrier than the MLV form for ropivacaine drug delivery.
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Amidas/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Sistemas de Liberação de Medicamentos/efeitos adversos , Fibroblastos/metabolismo , Queratinócitos/metabolismo , 2-Hidroxipropil-beta-Ciclodextrina , Apoptose/efeitos dos fármacos , Células Cultivadas , Humanos , Interleucina-10/metabolismo , Interleucina-1alfa/metabolismo , Interleucina-6/metabolismo , Lipossomos/efeitos adversos , Ropivacaina , Fator de Necrose Tumoral alfa/metabolismo , beta-Ciclodextrinas/efeitos adversosRESUMO
Objetivos: Determinar la actividad hipocolesterolémica y antioxidante del consumo crónico del extracto hidroalcohólico atomizado del maíz morado (Zea mays L) en ratas hipercolesterolémicas. Materiales y métodos: Se utilizaron cincogrupos de seis ratas Holtzmann cada uno, uno sin hipercolesterolemia (control negativo), y cuatro con hipercolesterolemia inducida por consumo de colesterol puro vía oral durante 60 días: control positivo y tres para las dosis de 250, 500 y 1000 mg/kg, respectivamente. En el día 60 se determinaron los niveles séricos de colesterol total, triglicéridos ycolesterol HDL (mg/dL), así como de malondialdehido (mmol/L) para determinar la actividad antioxidante. Se comparó la diferencias de medias con ANOVA y test de Tukey. Resultados: Se observó una disminución del colesterol total en las ratas hipercolesterolémicas que consumieron dosis de 250 y 500 mg/kg en relación con el grupo control positivo (reducción de 21,5 y 11,2 por ciento respectivamente, p menor que 0,01). No se observaron diferencias significativas sobre los niveles de triglicéridos y colesterol HDL. A mayor dosis se maíz morado se encontró una mayor reducción de radicales libres, conla dosis de 1000 mg/kg se redujo en 56,4 por ciento los niveles de malondialdehido (p menor que menor que 0,01). Conclusiones: En condiciones experimentales, el consumo crónico del extracto hidroalcohólico atomizado de maíz morado disminuye los niveles decolesterol total y aumenta la capacidad antioxidante.
Objetives: To determine the hypocholesterolemic antioxidant activity of the Andean purple corn (Zea mays L)hydroalcoholic extract atomized chronic consumption in hypercholesterolemic rats. Material and methods: Five groupsof six Holtzmann rats each were used, one without hypercholesterolemia (negative control), and four with inducedhypercholesterolemia by oral intake of pure cholesterol by 60 days: positive control and three for doses of 250, 500 y1000 mg/kg, respectively. In 60 day were determin the seric levels of total cholesterol, triglycerides and HDL cholesterol (mg/dL), as well as malondialdehyde (mmol/L) to determine the antioxidant activity. We compared the mean differneceswith ANOVA and Tukey test. Results: We observed a decrease in total cholesterol in hypercholesterolemic rats thatconsumed Andean purple corn doses of 250 and 500 mg/kg in compared whit positive control group (reduction of 21,5y 11,2 percentage respectively, pminor than 0,01). No significant differences in levels of triglycerides and HDL cholesterol were observed. A higher dose is purple corn was a further reduction of free radicals, with a dose of 1000 mg/kg decreased by 56.4 porcentage, levels of malondialdehyde (p minor than 0,01). Conclusions: In experimental conditions, the chronic consumption of the hydroalcoholic atomized extract of Andean purple corn decreased total cholesterol and increased the antioxidant capacity.