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The skin is the largest organ of the human body and has several functions such as barrier against external agents, the maintenance of temperature and homeostatic functions. Skin ageing is a natural process that can be influenced by environmental factors, intrinsic skin factors and lifestyle. UV light plays an important role in skin ageing and can cause spots, requiring the use of depigmenting agents. Nowadays, there is a great demand for ingredients that prevent skin ageing, with natural agents occupying a promising position. Among the natural agents, polyphenols, such as resveratrol and piceatannol, found in grapes, passion fruits and other fruits, have a huge relevance. Great benefits of piceatannol have been reported, so thus, this work focuses specifically on a review of the literature regarding the application of this polyphenol in skin care products. This polyphenol can be used in a wound-healing, or as anti-ageing, antioxidant, anti-acne and skin whitening, among other effects.
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Antioxidantes , Estilbenos , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Resveratrol/farmacología , Resveratrol/uso terapéutico , Estilbenos/farmacología , Estilbenos/uso terapéutico , PielRESUMEN
CONTEXT: Nanostructured lipid carrier (NLC) dispersions present low viscosity and poor mucoadhesive properties, which reduce the pre-corneal residence time and consequently, the bioavailability of ocular drugs. OBJECTIVE: The aim of this study was to prepare thermoresponsive eyedrops based on the combination of lipid nanoparticles and a thermoresponsive polymer with mucomimetic properties (Pluronic® F-127). MATERIALS AND METHODS: NLCi dispersions were prepared based on the melt-emulsification and ultrasonication technique. Physicochemical and morphological characteristics of the colloidal dispersions were evaluated. The formulation was also investigated for potential cytotoxicity in Y-79 human retinoblastoma cells and the in vitro drug release profile of the ibuprofen was determined. RESULTS: NLCi showed a Z-average below 200 nm, a highly positive zeta potential and an efficiency of encapsulation (EE) of â¼90%. The gelification of the NLCi dispersion with 15% (w/w) Pluronic® F-127 did not cause significant changes to the physicochemical properties. The potential NLC-induced cytotoxicity was evaluated by the Alamar Blue reduction assay in Y-79 cells, and no relevant cytotoxicity was observed after exposure to 0-100 µg/mL NLC for up to 72 hours. The optimized formulations showed a sustained release of ibuprofen over several hours. DISCUSSION AND CONCLUSION: The strategy proposed in this work can be successfully used to increase the bioavailability and the therapeutic efficacy of conventional eyedrops.
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Antiinflamatorios no Esteroideos/administración & dosificación , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Ibuprofeno/administración & dosificación , Lípidos/química , Nanoestructuras/química , Poloxámero/química , Antiinflamatorios no Esteroideos/efectos adversos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada , Portadores de Fármacos/efectos adversos , Liberación de Fármacos , Estabilidad de Medicamentos , Humanos , Ibuprofeno/efectos adversos , Lípidos/efectos adversos , Gotas Lubricantes para Ojos , Nanoestructuras/efectos adversos , Soluciones Oftálmicas , Poloxámero/efectos adversos , Reología , Propiedades de Superficie , ViscosidadRESUMEN
OBJECTIVE: The aim of this study was to develop and characterize suppositories for vaginal delivery of Lactobacillus acidophilus. METHODS: Formulations were performed in order to select suitable excipients based on suppository formation feasibility and cytotoxicity. Solid body and hollow-type suppositories were prepared by melting and molding using poly(ethylene glycol) (PEG) 400 and 4000 or Witepsol (WIT) H12 as excipients. L. acidophilus was incorporated in the molten mass before molding solid body suppositories or added as suspension into the cavity of hollow-type suppositories and sealed molten excipients. Cytotoxicity of the selected excipients was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and lactate dehydrogenase assays against VK2/E6E7, HEC-1-A and HeLa cells. Suppositories were characterized regarding organoleptic characteristics, mass uniformity, disintegration, breaking strength and L. acidophilus in vitro release. RESULTS: PEG 400, PEG 4000 and WIT H12 showed the absence of toxicity when tested using three different vaginal cell lines. Obtained vaginal suppositories presented uniform and mild texture, a content of about 1 × 10(8) colony-forming units, completely disintegrated in simulated vaginal environment in less than 60 min and provided sustained in vitro release of L. acidophilus. Release studies further demonstrated that incorporation of freeze-dried bacteria did not result in significant loss of viable bacteria, thus supporting that vaginal suppositories may possess good properties to promote the replacement of the vaginal flora in situations of urinary tract infection. CONCLUSION: Hollow-type suppositories showed to be promising delivery vehicles for vaginal delivery of probiotics.
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Excipientes/química , Lactobacillus acidophilus , Probióticos/administración & dosificación , Vagina/metabolismo , Administración Intravaginal , Línea Celular , Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos , Femenino , Células HeLa , Humanos , Polietilenglicoles/química , Probióticos/química , Probióticos/toxicidad , Supositorios , Triglicéridos/químicaRESUMEN
CONTEXT: Inclusion of antioxidants in topical formulations can contribute to minimize oxidative stress in the skin, which has been associated with photoaging, several dermatosis and cancer. OBJECTIVE: A Castanea sativa leaf extract with established antioxidant activity was incorporated into a semisolid surfactant-free formulation. The objective of this study was to perform a comprehensive characterization of this formulation. MATERIALS AND METHODS: Physical, microbiological and functional stability were evaluated during 6 months storage at 20 °C and 40 °C. Microstructure elucidation (cryo-SEM), in vitro release and in vivo moisturizing effect (Corneometer® CM 825) were also assessed. RESULTS AND DISCUSSION: Minor changes were observed in the textural and rheological properties of the formulation when stored at 20 °C for 6 months and the antioxidant activity of the plant extract remained constant throughout the storage period. Microbiological quality was confirmed at the end of the study. Under accelerated conditions, higher modifications of the evaluated parameters were observed. Cryo-SEM analysis revealed the presence of oil droplets dispersed into a gelified external phase. The release rate of the antioxidant compounds (610 ± 70 µgh(-0.5)) followed Higuchi model. A significant in vivo moisturizing effect was demonstrated, that lasted at least 4 h after product's application. CONCLUSION: The physical, functional and microbiological stability of the antioxidant formulation was established. Specific storage conditions should be recommended considering the influence of temperature on the stability. A skin hydration effect and good skin tolerance were also found which suggests that this preparation can be useful in the prevention or treatment of oxidative stress-mediated dysfunctions.
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Antioxidantes/química , Química Farmacéutica/métodos , Fagaceae , Extractos Vegetales/química , Hojas de la Planta , Tensoactivos , Administración Cutánea , Adulto , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Absorción Cutánea/efectos de los fármacos , Absorción Cutánea/fisiología , Adulto JovenRESUMEN
OBJECTIVE: We aimed to identify Portuguese women's experiences, preferences and perceptions regarding vaginal products. METHODS: A descriptive cross-sectional study was conducted (February-May 2013) among Portuguese women (aged 18 to 65 years) using an online questionnaire. Descriptive and chi-squared statistics were applied. RESULTS: Among 2529 women, 85.4% had used vaginal products, mostly to manage vulvovaginal infections (75.3%). Gels, creams and ointments (semi-solids) were the most frequently used (82%), followed by vaginal suppositories (56.5%) and tablets/capsules (41.8%), while vaginal rings were used by 10% of women. Semi-solids were preferred as an intravaginal medication both by women who had previously used them and by women who had never used an intravaginal product, while preference for vaginal rings was higher only among women who had previously used them. Even though 87.1% of all women considered vaginal drug delivery to be advantageous, the majority preferred to use oral products. Leakage (84.8%) and insertion difficulties (58.4%) were the main problems reported for vaginal products. CONCLUSIONS: Overall, semi-solids were the most used and preferred vaginal products, while vaginal rings were highly acceptable for women who had previously used them. Although they considered the vaginal route to be more efficient and safe, many women felt it to be less appealing than the oral route, particularly due to comfort issues.
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Comportamiento del Consumidor , Dispositivos Anticonceptivos Femeninos/estadística & datos numéricos , Vagina , Cremas, Espumas y Geles Vaginales/administración & dosificación , Administración Intravaginal , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Internet , Persona de Mediana Edad , Portugal , Encuestas y Cuestionarios , Enfermedades Vaginales/tratamiento farmacológico , Adulto JovenRESUMEN
The unique properties and characteristics of ocular tissues and the whole set of defence mechanisms of the ocular globe make the instillation of ocular drugs into a difficult task with a low rate of therapeutic response. One of the challenges for the new generation of ophthalmic pharmaceutical formulations is to increase the bioavailability of drugs administered by the ocular route and, therefore, their therapeutic efficacy. This can be achieved with the use of some strategies that provide an increase in the formulation pre-corneal residence time, mucoadhesion and penetration across the eye tissues. Colloidal carrier systems have been very successfully used for the selective and targeted delivery of drugs for several routes of administration. In this context, nanoparticles prepared with specific polymers or lipids and coated, dispersed or suspended in polymer solutions with mucoadhesion properties or in situ gelling properties will be an excellent strategy that deserves attention and further research. In this review, the characteristics and main properties of polymeric and lipid nanoparticles are discussed and examples and advantages of the application of these colloidal carrier systems for the ophthalmic administration of drugs are presented. The future directions of the research required in this specific field are also presented.
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Lípidos/química , Nanopartículas/química , Soluciones Oftálmicas/química , Preparaciones Farmacéuticas/química , Polímeros/química , Química Farmacéutica , HumanosRESUMEN
The specific interaction between cell surface receptors and corresponding antibodies has driven opportunities for developing targeted cancer therapies using nanoparticle systems. It is challenging to design and develop such targeted nanomedicines using antibody ligands, as the final nanoconjugate's specificity hinges on the cohesive functioning of its components. The multicomponent nature of antibody-conjugated nanoparticles also complicates the characterization process. Regardless of the type of nanoparticle, it is essential to perform physicochemical characterization to establish a solid foundation of knowledge and develop suitable preclinical studies. A meaningful physicochemical evaluation of antibody-conjugated nanoparticles should include determining the quantity and orientation of the antibodies, confirming the antibodies' integrity following attachment, and assessing the immunoreactivity of the obtained nanoconjugates. In this review, the authors describe the various techniques (electrophoresis, spectroscopy, colorimetric assays, immunoassays, etc.) used to analyze the physicochemical properties of nanoparticles functionalized with antibodies and discuss the main results.
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Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of nanoparticles given intravenously can reach a solid tumor. In situ-forming gels combined with nanoparticles facilitate local administration and promote drug retention at the tumor site. Injectable hydrogels based on poloxamer 407 are excellent candidates for this hybrid nanoparticle-hydrogel system because of their thermoresponsive behavior and biocompatibility. Therefore, this work aimed to develop injectable poloxamer hydrogels containing NLCs for intratumoral delivery of DTX. To ensure sterility, the obtained hydrogels were autoclaved (121 °C for 15 min) after preparation. Then, the incorporation of NLCs into the poloxamer hydrogels and the impact of steam sterilization on the nanocomposite hydrogels were evaluated concerning sol-gel transition, injectability, and physicochemical stability. All formulations were extruded through the tested syringe-needle systems with acceptable force (2.2-13.4 N) and work (49.5-317.7 N·mm) of injection. Following steam sterilization, injection became easier in most cases, and the physicochemical properties of all hydrogels remained practically unchanged according to the spectroscopical and thermal analysis. The rheological evaluation revealed that the nanocomposite hydrogels were liquid at 25 °C and underwent rapid gelation at 37 °C. However, their sterilized counterparts gelled at 1-2 °C above body temperature, suggesting that the autoclaving conditions employed had rendered these nanocomposite hydrogels unsuitable for local drug delivery.
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Hydrogels based on stimuli-responsive polymers can change their characteristics in response to small variations in environmental conditions, such as temperature, pH, and ionic strength, among others. In the case of some routes of administration, such as ophthalmic and parenteral, the formulations must meet specific requirements, namely sterility. Therefore, it is essential to study the effect of the sterilization method on the integrity of smart gel systems. Thus, this work aimed to study the effect of steam sterilization (121 °C, 15 min) on the properties of hydrogels based on the following stimuli-responsive polymers: Carbopol® 940, Pluronic® F-127, and sodium alginate. The properties of the prepared hydrogels-pH, texture, rheological behavior, and sol-gel phase transition-were evaluated to compare and identify the differences between sterilized and non-sterilized hydrogels. The influence of steam sterilization on physicochemical stability was also investigated by Fourier-transform infrared spectroscopy and differential scanning calorimetry. The results of this study showed that the Carbopol® 940 hydrogel was the one that suffered fewer changes in the studied properties after sterilization. By contrast, sterilization was found to cause slight changes in the Pluronic® F-127 hydrogel regarding gelation temperature/time, as well as a considerable decrease in the viscosity of the sodium alginate hydrogel. There were no considerable differences in the chemical and physical characteristics of the hydrogels after steam sterilization. It is possible to conclude that steam sterilization is suitable for Carbopol® 940 hydrogels. Contrarily, this technique does not seem adequate for the sterilization of alginate or Pluronic® F-127 hydrogels, as it could considerably alter their properties.
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The widespread push to invest in local cancer therapies comes from the need to overcome the limitations of systemic treatment options. In contrast to intravenous administration, local treatments using intratumoral or peritumoral injections are independent of tumor vasculature and allow high concentrations of therapeutic agents to reach the tumor site with minimal systemic toxicity. Injectable biodegradable hydrogels offer a clear advantage over other delivery systems because the former requires no surgical procedures and promotes drug retention at the tumor site. More precisely, in situ gelling systems based on poloxamers have garnered considerable attention due to their thermoresponsive behavior, biocompatibility, ease of preparation, and possible incorporation of different anticancer agents. Therefore, this review focuses on the use of injectable thermoresponsive hydrogels based on poloxamers and their physicochemical and biological characterization. It also includes a summary of these hydrogel applications in local cancer therapies using chemotherapy, phototherapy, immunotherapy, and gene therapy.
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The blood-brain barrier (BBB) restricts the access of therapeutic agents to the brain, complicating the treatment of neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), glioma, etc. To overcome this limitation and improve drug delivery to the central nervous system (CNS), the potential of nanocarriers, including lipid-based nanosystems, has been explored. Through active targeting, the surface of the nanocarriers can be modified with ligands that interact with the BBB, enhancing their uptake and penetration across the brain endothelium by different physiological mechanisms, such as receptor- or transporter-mediated transcytosis. This review seeks to provide an overview of active targeting in brain delivery, while highlighting the potential of functionalized lipid nanocarriers to treat brain diseases. Therefore, in the first sections, we discuss the importance of active targeting in CNS drug delivery, present the different ligands commonly used for functionalization, as well as summarize the state of the art of the most recent and relevant studies of surface-modified lipid nanosystems developed for neurological disorders. Lastly, challenges hindering clinical translation are discussed, and critical insights and future perspectives outlined. Although some limitations have been identified, it is expected that in the upcoming years these nanosystems will be an established approach.
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Enfermedad de Alzheimer , Nanopartículas , Humanos , Barrera Hematoencefálica , Ligandos , LípidosRESUMEN
Nanotechnology takes the lead in providing new therapeutic options for cancer patients. In the last decades, lipid-based nanoparticles-solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, and lipid-polymer hybrid nanoparticles-have received particular interest in anticancer drug delivery to solid tumors. To improve selectivity for target cells and, thus, therapeutic efficacy, lipid nanoparticles have been functionalized with antibodies that bind to receptors overexpressed in angiogenic endothelial cells or cancer cells. Most papers dealing with the preclinical results of antibody-conjugated nanoparticles claim low systemic toxicity and effective tumor inhibition, which have not been successfully translated into clinical use yet. This review aims to summarize the current "state-of-the-art" in anticancer drug delivery using antibody-functionalized lipid-based nanoparticles. It includes an update on promising candidates that entered clinical trials and some explanations for low translation success.
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Proteins and peptides are potential therapeutic agents, but their physiochemical properties make their use as drug substances challenging. Hydrogels are hydrophilic polymeric networks that can swell and retain high amounts of water or biological fluids without being dissolved. Due to their biocompatibility, their porous structure, which enables the transport of various peptides and proteins, and their protective effect against degradation, hydrogels have gained prominence as ideal carriers for these molecules' delivery. Particularly, stimuli-responsive hydrogels exhibit physicochemical transitions in response to subtle modifications in the surrounding environment, leading to the controlled release of entrapped proteins or peptides. This review is focused on the application of these hydrogels in protein and peptide delivery, including a brief overview of therapeutic proteins and types of stimuli-responsive polymers.
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Topical drug treatment aims at providing high concentrations of drugs at the site of application so as to avoid adverse systemic effects associated with oral administration. Smart polymers, or stimuli-responsive polymers, are able to respond to a stimulus by showing physical or chemical changes in their behaviour as, for example, the delivery of the drug carried by them. The thermo-responsive nature of Pluronic® F-127 (Basf, Ludwigshafen, Germany) makes it an excellent candidate for the delivery of drugs at various application sites. In recent years, PF-127, and later, Pluronic lecithin organogels (PLO), have attracted particular interest in the design of dermal and transdermal delivery systems with a view to promoting, improving or retarding drug permeation through the skin, bearing in mind that for topical delivery systems, accumulation in the skin with minimal permeation is desired, while for systemic delivery, the opposite behaviour is preferred. In this review, we discuss the properties and characteristics of PF-127 and Pluronic lecithin organogels (PLO), and present many examples and advantages of the application of these polymeric systems in topical and transdermal administration of drugs. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
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Lecitinas/administración & dosificación , Lecitinas/química , Poloxámero/administración & dosificación , Poloxámero/química , Piel/metabolismo , Administración Cutánea , Animales , Sistemas de Liberación de Medicamentos/métodos , HumanosRESUMEN
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood-brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94-98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 µM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain.
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This study aims to design and characterize Nanostructured lipid carriers (NLC) and Nanostructured lipid carrier-based hydrogels with Passiflora edulis seeds oil, a by-product from Madeira Island food industry. NLC were prepared by the ultrasonication technique, using passion fruit seeds oil as a liquid lipid and glyceryl distearate as a solid lipid. These NLC were then gelled with Poly (acrylic acid). Long-term stability studies were conducted with NLC and NLC-based hydrogels stored for 12 months. The following tests were performed: morphology, encapsulation efficiency, particle size analysis, polydispersity index analysis, zeta potential, pH measurement, color analysis, viscosity studies, texture analysis, in vitro occlusion test, ex vivo skin penetration study, tyrosinase inhibition activity, in vitro skin permeation experiments and in vitro cytotoxicity studies. The developed NLC had spherical shape and narrow particle sizes distribution with mean sizes in the range of 150 nm and PDI below 0.3, Zeta potential values around -30 mV and high Encapsulation efficiency. The tyrosinase inhibitory activity and skin retention of the nanoparticles was superior to that of the non-encapsulated oil. The developed formulations did not show cytotoxicity towards HaCat cells and presented suitable viscosity and texture properties for skin application, proving to be good candidates as depigmenting agent.
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Nanoestructuras , Passiflora , Portadores de Fármacos , Hidrogeles , Lípidos , Tamaño de la Partícula , Absorción CutáneaRESUMEN
Neurodegenerative diseases (NDs) bear a lot of weight in public health. By studying the properties of the blood-brain barrier (BBB) and its fundamental interactions with the central nervous system (CNS), it is possible to improve the understanding of the pathological mechanisms behind these disorders and create new and better strategies to improve bioavailability and therapeutic efficiency, such as nanocarriers. Microfluidics is an intersectional field with many applications. Microfluidic systems can be an invaluable tool to accurately simulate the BBB microenvironment, as well as develop, in a reproducible manner, drug delivery systems with well-defined physicochemical characteristics. This review provides an overview of the most recent advances on microfluidic devices for CNS-targeted studies. Firstly, the importance of the BBB will be addressed, and different experimental BBB models will be briefly discussed. Subsequently, microfluidic-integrated BBB models (BBB/brain-on-a-chip) are introduced and the state of the art reviewed, with special emphasis on their use to study NDs. Additionally, the microfluidic preparation of nanocarriers and other compounds for CNS delivery has been covered. The last section focuses on current challenges and future perspectives of microfluidic experimentation.
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Recently, studies on the by-products from the food industry, such as passion fruit seeds, have significantly increased, as these can have an added value, due to their properties, such as potential antioxidant activity. This study was conducted to determine the presence of piceatannol and resveratrol in various extracts of passion fruit (Passiflora edulis) seeds from Madeira Island and a commercial passion fruit oil was used as reference. The commercial oil and the extracts that were obtained by traditional Soxhlet method with ethanol and acetone did not reveal the presence of the two stilbenes, piceatannol and resveratrol. However, the extracts that were obtained by the ultrasound method showed significant amounts of piceatannol and resveratrol when compared with the commercial oil. The presence of these compounds indicates that this oil could have potential application in cosmetic and pharmaceutical industries, due to their proven antioxidant and anti-aging properties.
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The objective of this work was to investigate the main theological features of vaginal hydrophilic polymer gels and to elucidate about the relationship between these characteristics and gels composition, and their general influence in therapeutic/usage purpose. Flow and dynamic oscillatory properties of four commercially available (Conceptrol, Gynol II, RepHresh, and Replens) and two investigational vaginal gels were determined by cone-and-plate rheometry, at body temperature. Several parameters (apparent viscosity, complex viscosity, storage modulus, loss modulus, critical oscillatory stress, tan delta, thixotropy and yield stress) were measured and/or calculated. Gels presented non-Newtonian, pseudoplastic, thixotropic behavior, with yield stress. Overall viscosities varied between 13500 Pa.s and approximately 80 Pa.s within a biologically relevant shear rate interval (0.01-100 s(-1)). Yield stress values were variable between different determination methods but coherent in terms of ranking. Also, tested gels showed viscoelastic properties, being characterized by predominant elastic solid-like behavior. Rheological behavior of vaginal gels strongly depended on the type of gelling agent used, which potentially influences their spreading and retention properties when administered in the vaginal canal. Small variations in gels composition can result in substantial changes in their features, namely viscosity, yield stress and thixotropy. Rheological properties of tested gels appeared to be correlated with their therapeutic/usage purpose.