Formulation, characterization and and evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement.

OBJECTIVE: To prepare aloe-emodin solid dispersion (AE-SD) and determine the metabolic process of AE and AE-SD in vivo. METHODS: AE-SD was prepared viasolvent evaporation or solvent melting using PEG-6000 and PVP-K30 as carriers. Thermogravimetric analysis, X-ray diffraction spectroscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of AE-SD. Optimal prescriptions were screened viathe dissolution degree determination method. Using Phoenix software, AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid dispersion. Acute toxicity was assessed in mice, and the physiological toxicity was used as the determination criterion for toxicity. RESULTS: AE-SD showed that AE existed in the carrier in an amorphous state. Compared with polyethylene glycol, polyvinylpyrrolidone (PVP) inhibited AE crystallization, causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug dispersion. Therefore, it was more suitable as a carrier material for AE-SD. The addition of poloxamer (POL) was more beneficial to the stability of solid dispersions and could reduce the amount of PVP. The dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1：2：2, and its dissolution effect was also optimal. Based on the pharmacokinetic comparison, the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE, the Cmax of AE-SD was greater than that of AE, and t1/2 and mean residence time of AE-SD were less than AE. The results showed that the drug metabolism in AE-SD was better, and the residence time was shorter. The toxicology study showed that both AE and AE-SD had no toxicity. CONCLUSION: This paper established that the solubility of the drug could be increased after preparing a solid dispersion, as demonstrated by in vitro dissolution experiments. In vivo pharmacokinetics studies confirmed that AE-SD could improve the bioavailability of AE in vivo, providing a new concept for the research and development of AE preparations.

Application of a novel PhysioCell apparatus for biopredictive dissolution tests of oral immediate release formulations - A case study workflow for in vitro-in vivo predictions.

Biorelevant dissolution tests of oral solid dosage forms open the gate to valid in vitro-in vivo predictions (IVIVP). A recently developed apparatus, PhysioCell, allows mimicking the fluid flow and pressure waves occurring in the human fasted stomach. In this work, we used the PhysioCell to perform IVIVP for vortioxetine immediate-release (IR) tablets: the originator (Brintellix) and generic product candidates (VORTIO). The dissolved drug was monitored in the gastric (StressCell) and intestinal (Collection Vessel) compartments that contained biorelevant media. Simulated intermittent gastric stress at 15 min and "housekeeping wave" at 30 min increased the dissolution of Brintellix formulations only. A mechanistic model that best described the observations involved the first-order tablet disintegration with a stress-induced enhancement for Brintellix, dissolution of solid particles in the StressCell, and drug transfer to the Collection Vessel. Then, a semi-mechanistic pharmacokinetic model with dissolution parameters as inputs simulated vortioxetine plasma concentrations in healthy volunteers after single and multiple dosing of Brintellix. Despite different dissolution characteristics, VORTIO provided similar concentration profiles to the originator. In conclusion, PhysioCell dissolution tests, combined with semi-mechanistic IVIVP, can be successfully used to develop IR dosage forms exhibiting gastric stress-related effects.

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.

Vitamin E Lipid-Based Nanodevices as a Tool for Ovine Sperm Protection against Oxidative Stress: Impact on Sperm Motility.

The advent of nanotechnology in the field of animal reproduction has led to the development of safer and more efficient therapies. The use of nanotechnology allows us to avoid the detrimental effects of certain traditional antioxidants, such as Vitamin E. Its hydrophobic nature makes mandatory the use of organic solvents, which are toxic to sperm cells. This study aims to evaluate the efficiency of vitamin E nanoemulsions (NE) on ram (Ovis aries) spermatozoa. For this purpose, the effect of three NE concentrations (6, 12, and 24 mM) were assessed on sperm of 10 mature rams of the Manchega breed. Sperm samples were collected by artificial vagina, pooled, and diluted in Bovine Gamete Medium. The samples were stored at 37 °C and assessed at 0, 4, 8, and 24 h under oxidative stress conditions (100 µM Fe2+/ascorbate). Motility (CASA), viability (YO-PRO/IP), acrosomal integrity (PNA-FITC/IP), mitochondrial membrane potential (Mitotracker Deep Red 633), lipoperoxidation (C11 BODIPY 581/591), intracellular reactive oxygen species (ROS) production and DNA status (SCSA®®) were assessed. A linear mixed-effects models were used to analyze the effects of time, NE, and oxidant (fixed factors) on sperm parameters, and a random effect on the male was also included in the model with Tukey's post hoc test. Protection of ram spermatozoa with NE resulted in a more vigorous motility under oxidative stress conditions with respect Control and Free vitamin E, while preventing the deleterious effects of oxidative stress coming from the production of free radicals and lipid peroxidation. These results ascertain the high relevance of the use of delivery systems for sperm physiology preservation in the context of assisted reproduction techniques.

Putting midodrine on the MAP: An approach to liberation from intravenous vasopressors in vasodilatory shock.

PURPOSE: Prolonged duration of intravenous (IV) vasopressor dependence in critically ill adult patients with vasodilatory shock results in increased length of stay in both the intensive care unit (ICU) and hospital, translating to higher risk of infection, delirium, immobility, and cost. Acceleration of vasopressor liberation can aid in reducing these risks. Midodrine is an oral α 1-adrenergic receptor agonist that offers a potential means of liberating patients from IV vasopressor therapy. This clinical review summarizes primary literature and proposes a clinical application for midodrine in the recovery phase of vasodilatory shock. SUMMARY: Five studies with a total of over 1,000 patients conducted between 2011 and 2021 were identified. In observational studies, midodrine administration was demonstrated to lead to faster time to liberation from IV vasopressor therapy and shorter ICU length of stay in patients recovering from vasodilatory shock. These findings were not replicated in a prospective, multicenter, randomized controlled trial. In this review, literature evaluating midodrine use for IV vasopressor liberation is summarized and study limitations are discussed. CONCLUSION: On the basis of this review of current literature, recommendations are provided on selecting appropriate candidates for adjunctive midodrine in the recovery phase of vasodilatory shock and considerations are discussed for safely and effectively initiating, titrating, and discontinuing therapy.

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.

Synthesis and Characterization of Nanoporous Carbon Carriers for Losartan Potassium Delivery.

Losartan potassium is most commonly used for the treatment of hypertension. In recent years, new applications of this drug have emerged, encouraging the design of novel nanoporous carriers for its adsorption and release. The purpose of this study was to synthesize ordered mesoporous carbon vehicles via a soft-templating method altered with the use of nitrogen precursors and via a hard-templating method followed by chitosan functionalization. As a result, the materials obtained differed in nitrogen content as well as in the number of total surface functional groups. The impact of the modification on the physicochemical properties of carbon carriers and their interaction with losartan potassium during adsorption and release processes was examined. The materials were characterized by various morphologies, specific surface areas (101-1180 m2 g-1), and the amount of acidic/basic oxygen-containing functional groups (1.26-4.27 mmol g-1). These features, along with pore sizes and volumes, had a key effect on the sorption capacity of carbon carriers towards losartan potassium (59-161 mg g-1). Moreover, they contributed to the differential release of the drug (18.56-90.46%). Losartan potassium adsorption onto the surface of carbonaceous materials was mainly based on the formation of hydrogen bonds and π-π interactions and followed the Langmuir type isotherm. It has been shown that the choice of the method of carbon carriers' synthesis and their modification allows for the precise control of the kinetics of the losartan potassium release from their surface, resulting in rapid or sustained drug liberation.

Towards functional characterization of excipients for oral solid dosage forms using UV-vis imaging. Liberation, release and dissolution.

The purpose of this study was to investigate whole-dosage form UV-vis imaging as a potential tool for functional characterization of excipients used in solid oral dosage forms. To this end, tablets (average mass 260.0 mg, 224.5 mg and 222.1 mg) containing theophylline anhydrate (20 % w/w), 1% (w/w) magnesium stearate, and 79 % (w/w) of either microcrystalline cellulose (MCC, Avicel PH 101) or hydroxypropyl methylcellulose (HPMC, Methocel K15 M or K100 M) were prepared as model systems. Drug liberation from tablets was studied in 0.01 M HCl at 37 °C using a Sirius SDi2 equipped with a USP IV type flow cell comprising a UV-vis imaging detector operating at 255 nm and 520 nm. The effluent from the flow cell was passed through a downstream spectrophotometer, and UV-vis spectra in the wavelength range 200-800 nm were recorded every 2 min. The erosion and swelling behavior of the MCC tablets and HPMC K15 M and K100 M tablets were visualized in real time. The swelling of HPMC K15 M and K100 M containing tablets was assessed quantitatively as changes in tablet diameter measured at 520 nm, and was clearly distinguished from the swelling of the MCC tablets. Namely, an increment of 2.5 mm in diameter was determined for the HPMC tablets while the MCC tablets increased by 0.5-1 mm in diameter. Gel layers of variable thickness were observed only for the HPMC K15 M and K100 M tablets. In addition, a relatively high initial liberation rate of theophylline was found for the MCC tablets as compared to the HPMC tablets. UV-vis imaging revealed features of liberation not revealed by simply measuring drug concentration in the dissolution media or by visual assessment. It may be sufficiently sensitive to be further developed for functional characterization of excipients and provide insights into drug-excipient interactions likely to be useful in formulation development.

Albumin and functionalized albumin nanoparticles: production strategies, characterization, and target indications.

The inherent properties of albumin facilitate its effective use as a raw material to prepare a nanosized drug delivery vehicles. Because of the enhanced surface area, biocompatibility, and extended half-life of albumin nanoparticles, a number of drugs have been incorporated in albumin matrices in recent years. Furthermore, its ability to be conjugated to various receptor ligands makes albumin an ideal candidate for the increased delivery of drugs to specific sites. The present review provides an in-depth discussion of production strategies for the preparation of albumin and conjugated albumin nanoparticles and for the targeting of these formulations to specific organs and cancer cells. This review also provides insights into drug loading, release patterns, and cytotoxicity of various drug-loaded albumin nanoparticles.

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.

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.

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

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.

Intraoral Device for Optimal Antifungal Delivery in a Rat Model.

BACKGROUND: Antifungal agents incorporated into temporary denture resilient liners as drug carriers and delivery have been suggested as an alternative treatment for denture stomatitis. However, to test the in vivo biocompatibility of this protocol, standardization of an intraoral device for optimal drug delivery is required. OBJECTIVE: Standardized criteria were produced to adjust an acrylic intraoral device (IOD) for rats feasible for denture stomatitis treatment by sustained drug-delivery based on minimal inhibitory drug concentrations (MICs) of antifungals for Candida albicans biofilm. METHOD: Adjustments methodological involved diet, impression technique, type of retention device to the palate and histopathological analysis. 115 Wistar rats were tested without IOD, with devices without relining or relined with temporary resilient material (Trusoft) modified or not by drugs at MICs (nystatin-0.032g/mL; chlorhexidine diacetate-0.064g/mL; ketoconazole-0.128g/mL). The animals were sacrificed after 7 or 14 days from the IOD installation. RESULTS: Paste diet enabled the best animal survival conditions. The IODs that most satisfactorily remained in position were those designed only to the posterior palatal mucosa and cement-retained in molars, being all obtained from impressions highly detained and individual. In both periods, Trusoft without/with drugs showed good performance. Only histological samples from hard/soft tissues were considered appropriate for region of interest-RI determination (n=12), which corresponded to the area restricted to the first molars between the palatal neurovascular bundles. Final samples of all groups allowed a standardized descriptive histopathological analysis in both periods. CONCLUSION: The methodological standardization of this rat model resulted in IODs for optimal antifungal delivery for denture stomatitis treatment.

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)