Micro/nano hierarchical structure of titanium surface promotes MC3T3-E1 adhesion proliferation and drug loading potential evaluation / 口腔疾病防治

Objective @# To investigate the effect of micro/nano hierarchical structures on the adhesion and proliferation of MC3T3-E1 cells, evaluate the drug delivery potential of titanium surfaces, and provide a reference for the modification of selected areas of titanium surfaces to enhance drug delivery and slow drug release. @*Methods @# Pure titanium samples (10 mm in diameter and 2.5 mm in thickness) were randomly divided into a polished group (T), anodized group (TO), and micro/nano hierarchical structure group (FTO) according to the surface treatment of the titanium. The T group was polished, the TO group was treated with anodic oxidation technology, and the FTO group was treated by femtosecond laser etching combined with anodic oxidation technology. The three surface morphologies were observed by scanning electron microscopy (SEM), the wettability of the surface was measured by the contact angle, and the surface chemical composition was analyzed by X-ray energy dispersive spectroscopy (EDS). The depth of the FTO structure and the surface roughness were measured by confocal laser scanning microscopy (CLSM). MC3T3-E1 cell adhesion proliferation and differentiation on the surface of each group of samples was assessed by immunofluorescence staining, CCK-8, and semiquantitative analysis of Alizarin staining. A freeze-drying method was applied to load recombinant human bone morphogenetic protein-2 (rhBMP-2), and an enzyme-linked immunosorbent assay (ELISA) was used to assess the drug-loading potential of different surface structures. @* Results@#SEM revealed that the surface of T group titanium plates showed uniform polishing marks in the same direction. The surface of the TO group was a nanoscale honeycomb-like titanium dioxide (TiO2) nanotube structure, and the FTO group formed a regular and ordered micro/nano layered structure. The contact angle of the FTO group was the smallest at 32° ± 1.7°. Its wettability was the best. The average depth of the first-level structure circular pores was 93.6 μm, and the roughness was 1.5-2 μm. The TO and FTO groups contained a high percentage of oxygen, suggesting TiO2 nanotube formation. The FTO group had the most significant surface cell proliferation (P<0.001) and the largest cell adhesion surface area (P<0.05). rhBMP-2 was slowly released for 14 d after loading in the FTO group and promoted extracellular matrix mineralization (P<0.001). @*Conclusion @#Titanium surface microprepared hierarchical structure has the effect of promoting MC3T3-E1 cell adhesion, proliferation, and osteogenic differentiation with drug loading potential, which is a new method of titanium surface treatment.

Research progress in spatiotemporal sustained release of growth factors in bone tissue engineering / 中华创伤杂志

The spatiotemporal distribution of growth factors in bone tissue-engineered repair and reconstruction is critical. Growth factors can be used in bone tissue engineering through different encapsulation methods. Different encapsulation methods make growth factors have different release kinetics. At present, the common physical entrapment, easily degradable carrier and simple spatial structure usually result in poor sustained release of growth factors by burst release. The optimization of release methods of growth factors enables their release at different times and spaces in a biomimetric manner, which is conducive to improving the effect of tissue repair and avoiding the adverse effects of excessive factors. Starting from the necessity of spatiotemporal sustained release of growth factors, the authors summarize growth factors can attain spatiotemporal sustained release by being directly immobilized on the surface of the carrier, encapsulated in the carrier, encapsulated in the microparticles and encapsulated in the carrier by the microparticles and review the spatiotemporal sustained release of growth factors in different encapsulation methods, so as to provide a reference for optimizing spatiotemporal release of growth factor in bone tissue engineering.

Simultaneous determination of anti-diabetic drugs

A novel reverse phase, isocratic HPLC method is described to separate five anti-diabetic drugs i.e., glimepiride, metformin, sitagliptin, rosiglitazone and pioglitazone. Nucleosil C18 analytical column was used as stationary phase, while mobile phase consisted of acetonitrile:phosphate buffer: methanol (40/40/20, v/v) pH 2.0. Effluent was monitored at a flow rate 1 mL/min and detected at wavelength of 240 nm. This research produced excellent chromatography over a wide concentration range of 25-10000 ng/mL. Sepprated and well resolved quantifiable peaks were obtained and test results were linear in this range. Correlation coefficient of more than 0.9990 was witnessed as well as Low %RSD values i.e., maximum 2.0% documented excellent precision of the method. Good recoveries from pharmaecutical (99-101%), urine and plasma samples (>96%) in a range of concentrtion granted very good linearity, accuracy and precision. The projected method has satisfactory applications in quality control of these molecules as well as quantification of these molecules in urine and plasma samples.

Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles

Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, ß-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-ß-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 µg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-ß-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-ß-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates

Sutures modified by incorporation of chlorhexidine and cinnamaldehyde: anti-Candida effect, bioavailability and mechanical properties / Suturas modificadas pela incorporação de clorexidina e cinamaldeído: efeito anti-Candida, biodisponibilidade e propriedades mecânicas

Abstract Introduction Antimicrobial sutures are a therapeutic alternative for the control of oral infections. Objective Incorporate Chlorhexidine (CHX) and Cinnamaldehyde (CN) in sutures and evaluate the anti-Candida effect, release of antimicrobials and mechanical properties. Material and method Silk (S) and Polyglactin 910 (P) sutures were aseptically sectioned (20 mm) and immersed for incorporation in 0.12% CHX, 0.4% CN and 0.9% saline solutions under stirring for 60 minutes (n = 10 / group). Suspensions of 500 μL of Candida albicans (ATCC 90028/ 1 × 106 CFU/mL) were used to evaluate fungal adhesion after the 48 h period at 37°C. The release of CLX and CN were evaluated at 0, 24 and 48 hours (n=3/group) by UV-VIS spectrophotometer (275 nm). The tensile strength and displacement (n=5/group) were evaluated after incorporation (30 mm/min, 50N). Data were analyzed by Anova and Tukey (α = 5%). Result No anti-Candida effect was observed on S and P sutures incorporated with CLX and CN (p>0.05). However, progressive release was verified up to 48 after treatment with CLX (S = 0.075 / P = 0.073 μg/mL) and CN (S = 35.33 /P= 5.72 μg/mL). There was a decrease in tensile strength in S (CLX = 9.9 / CN = 9.9 N) and P (CLX = 14.4 / CN = 15.5 N) (p<0.05). No differences were observed for the displacement for S (CLX = 19.3 / CN=20.7 mm) and P (CLX = 16.2 / CN=15.8 mm) (p>0.05). Conclusion The incorporation of CLX and CN did not have a positive effect on the biological and mechanical properties of the sutures evaluated.

Resumo Introdução Fios de suturas com antimicrobianos são uma alternativa terapêutica para o controle de infecções orais. Objetivo Incorporar Clorexidina (CHX) e Cinamaldeído (CN) em fios de sutura e avaliar o efeito anti-Candida, liberação de antimicrobianos e as propriedades mecânicas. Material e método Fios de Seda (S) e Poliglactina 910 (P) foram seccionadas assepticamente (20 mm) e imersos para incorporação em CHX a 0,12%, CN a 0,4% e solução fisiológica a 0,9% sob agitação por 60 minutos (n = 10 / grupo). Suspensões de 500 μL de Candida albicans (ATCC 90028/1 × 106 UFC / mL) foram utilizadas para avaliar a aderência fúngica após o período de 48 horas a 37 ° C. A liberação de CLX e CN foi avaliada em 0, 24 e 48 horas (n = 3 / grupo) por espectrofotômetro UV-VIS (275 nm). A resistência à tração e o deslocamento (n = 5 / grupo) foram avaliados após a incorporação (30 mm / min, 50N). Os dados foram analisados ​​por Anova e Tukey (α = 5%). Resultado Não foi observado efeito anti-Candida nas suturas S e P incorporadas com CLX e CN (p> 0,05). No entanto, a liberação progressiva foi verificada até 48 após o tratamento com CLX (S = 0,075 / P = 0,073 μg / mL) e CN (S = 35,33 / P= 5,72 μg / mL). Houve uma diminuição na resistência à tração em S (CLX = 9,9 / CN = 9,9 N) e P (CLX = 14,4 / CN = 15,5 N) (p <0,05). Não foram observadas diferenças para o deslocamento para S (CLX = 19,3 / CN=20,7 mm) e P (CLX = 16,2 /CN= 15,8 mm) (p> 0,05). Conclusão A incorporação de CLX e CN não teve efeito positivo sobre as propriedades biológicas e mecânicas das suturas avaliadas.

Evaluación de la intercambiabilidad in vitro de diferentes marcas de tabletas de diclofenaco sódico disponibles en el mercado colombiano / In vitro evaluation of the interchangeability of different brands of diclofenac sodium tablets available in the Colombian market

Introducción. El diclofenaco sódico se clasifica como un antiinflamatorio no esteroide. Dado que es de venta libre, el paciente no tiene ningún seguimiento por parte de los equipos de salud, y como sus fuentes son múltiples, es necesario establecer la equivalencia entre ellas en estudios in vitro, que son los más prácticos y plantean un menor compromiso ético. Objetivos. Determinar la intercambiabilidad de diferentes marcas comerciales de diclofenaco sódico comparadas con el producto innovador mediante un estudio in vitro de tabletas comerciales de 50 mg, según los lineamientos del Sistema de Clasificación Biofarmacéutica (SCB). Materiales y métodos. Se desarrollaron pruebas físicas y químicas siguiendo las indicaciones de laedición 39 de la United States Pharmacopeia (USP). Para la cuantificación, se validó una metodología analítica según lo establecido en la mencionada farmacopea y la guía Q2 del International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Los perfiles de disolución y sus análisis se rigieron por lo establecido por la Organización Mundial de la Salud y las normas nacionales. Resultados. Todos los productos aprobaron las pruebas físicas. En cuanto a la disolución, la etapa ácida también fue superada por todas las marcas, pero una marca falló en la etapa alcalina. El análisis de similitud reveló que solo un producto fue equivalente al innovador y tres fueron supradisponibles, aunque dichas marcas también podrían considerarse equivalentes al producto innovador. Conclusiones. De las ocho marcas evaluadas, tres no cumplieron totalmente con la prueba de valoración del principio activo y del porcentaje de disolución; solo una marca fue intercambiable con el producto innovador y tres fueron supradisponibles comparadas con este, por lo cual no constituyen un riesgo para el paciente.

Introduction: Diclofenac sodium is classified as a non-steroidal anti-inflammatory drug. As diclofenac is an over-the-counter drug, its use among patients cannot be monitored by health teams in follow-up sessions. Given the multiple sources of diclofenac sodium, their interchangeability must be investigated, particularly in the form of in vitro studies, which are the most practical research type and entail minimal ethical commitment. Objectives: To determine the interchangeability of the different commercial brands of diclofenac sodium relative to the innovative product, this work carries out an in vitro study of eight commercial products of diclofenac sodium (50 mg) following the guidelines of the Biopharmaceutical Classification System. Materials and methods: Physical and chemical tests were developed following the guidelines of the 39th edition of the United States Pharmacopoeia. An analytical methodology was validated for the quantification of diclofenac according to the current pharmacopoeia and the Q2 guideline ofthe International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Dissolution profiles and their analyseswere governed by the regulations established by the World Health Organization and the national regulations. Results: All the products passed the physical tests. In the dissolution assays, the acid stage was overcome by all brands, but in the alkaline stage, one brand failed. The analysis of the similarities revealed that only one product was equivalent to the innovator and that three were supra-available, although these brands could also be considered equivalent to the innovator. Conclusions: Of the eight brands evaluated, three failed the test forthe active principle and the percentage of dissolution. Only one brand was found to be interchangeable with the innovator, and three were identified to besupra-availableand, thus, they do not present a risk for patients.

Biocompatibilidade in vivo de material resiliente temporário para base de prótese modificado por antimicrobianos para tratamento da estomatite protética / Biocompatibility in vivo of temporary soft denture liner for denture base modified by antimicrobials agents for denture stomatitis treatment

Reembasadores resilientes temporários contendo fármacos antifúngicos foram sugeridos como um tratamento adjunto para estomatite protética. No entanto, antes de utilizar clinicamente estes reembasadores modificados em humanos, é importante avaliar a sua biocompatibilidade em modelos animais. Este estudo avaliou a biocompatibilidade in vivo de um reembasador resiliente temporário para base de prótese (Trusoft) modificado por agentes antimicrobianos em suas mínimas concentrações inibitórias (MCIs) para biofilme de Candida albicans. Dispositivos acrílicos intra-orais (DIOs) foram confeccionados individualmente para 60 ratos Wistar. Os ratos foram divididos em 6 grupos (n=5): 3 grupos controle (Negativo: sem DIO; Geral: DIO sem reembasamento; Positivo: DIO reembasado com Trusoft sem fármacos) e 3 grupos experimentais (DIOs reembasados com Trusoft modificados por fármacos em suas respectivas MCIs: 0,032 g de nistatina, 0,064 g de diacetato de clorexidina e 0,128 g de cetoconazol). Os ratos com ou sem os DIOs foram eutanasiados após 7 e 14 dias de avaliação. A análise histopatológica qualitativa foi realizada comparando-se fotomicrografias de secções histológicas, que foram obtidas utilizando um microscópio óptico que abrangeu transversalmente a região intermolares. As alterações morfológicas no epitélio e queratina foram analisadas quantitativamente através da realização de planimetria computadorizada. Os dados quantitativos foram analisados utilizando ANOVA 2-fatores e teste de Tukey (=0,05). A análise quantitativa mostrou que apenas o grupo com DIO contendo cetoconazol diminuiu significativamente a espessura e a área do estrato córneo em comparação com os outros grupos (p<0,05), que não apresentaram diferenças significativas entre si (p>0,05). Estes resultados estiveram de acordo com os obtidos para análise qualitativa. A incorporação de MCIs de nistatina e diacetato de clorexidina no Trusoft não induziram alterações histopatológicas na mucosa palatina de ratos, sugerindo a biocompatibilidade in vivo deste protocolo para o tratamento de estomatite protética.(AU)

Temporary resilient denture liners containing antifungal drugs have been suggested as an adjunct treatment for denture stomatitis. However, before clinically using these modified liners in humans, it is important to assess their biocompatibility in animal models. This study evaluated the in vivo biocompatibility of a temporary soft denture liner (Trusoft) modified by antimicrobial agents at their minimum inhibitory concentrations (MICs) for biofilm formation by Candida albicans. Methods: Acrylic intraoral devices (IODs) were individually made for 60 Wistar rats. The rats were divided into the following 6 groups (n=5): 3 control groups (Negative: without IOD; General: IOD without relining; Positive: IOD relined with Trusoft without drugs) and 3 experimental groups (IOD relined with Trusoft modified by drugs at MICs: 0.032 g for nystatin, 0.064 g for chlorhexidine diacetate, and 0.128 g for ketoconazole). The rats with or without the IODs were sacrificed after 7 or 14 days of evaluation. Histopathological qualitative analysis was performed by comparing photomicrographs of histological sections, which were obtained using an optical microscope that transversely covered the inter-molar region. Morphological changes in the epithelium and keratin were quantitatively analyzed by performing computerized planimetry. Quantitative data were analyzed using 2-way ANOVA and Tukey's test (=0.05). Quantitative analysis showed that only the group with IOD containing ketoconazole significantly decreased the thickness and area of the stratum corneum compared with the other groups (p<0.05), which showed no significant differences between each other (p>0.05). These results were in accordance with those obtained for qualitative analysis. Incorporation of MICs of nystatin and chlorhexidine diacetate in Trusoft did not induce histopathological changes in the palatal mucosa of rats, suggesting the in vivo biocompatibility of this protocol for treating denture stomatitis.(AU)