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Apart from the use of sun therapy for the cure of many skin diseases and disorders of bygone days, nowadays artificial light sources of a narrowband (NB) ultraviolet-B (UV-B) have effectively revolutionized the treatment of such skin diseases. The crucial role of gadolinium (Gd3+) ions in calcium-based hosts lies in their narrowband emission spectrum, specifically at 311-315 nm, attributed to the 6P7/2 to 8S7/2 transition. Calcium-based materials, known for their chemical stability, facilitate Gd3+ embedding, enabling UV activation and express emission in the narrowband range. This emission spectrum is well-suited for skin treatments, aligning with the action spectrum of various skin diseases. Gd3+ activated host materials in fluorescent lamps are considered prime sources of NB-UVB emissions. Calcium-based host materials are proving to be popular environments for embedding of dopants for such emissions. Calcium-based phosphor materials are leading the research in phototherapy applications due to their strong UV-B emissions, especially when activated by Gd3+ ions. Applications of phosphor host materials of this nature are generally chemically and thermally stable, have a low synthesis temperature and which produce enhanced NB-UVB emissions specifically suited for phototherapy lamps. This paper is a review of calcium -based phosphor host materials in Gd3+ activated materials or through energy transfers from sensitized dopant ions for enhanced NB-UVB emissions that is pertinent for treatments of many skin diseases such as psoriasis, vitiligo, eczema, and many other skin conditions.
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Quercetin, a bioactive plant flavonoid, is an antioxidant, and as such it exhibits numerous beneficial properties including anti-inflammatory, antiallergic, antibacterial and antiviral activity. It occurs naturally in fruit and vegetables such as apples, blueberries, cranberries, lettuce, and is present in plant waste such as onion peel or grape pomace which constitute good sources of quercetin for technological or pharmaceutical purposes. The presented study focuses on the role of quercetin in prevention and treatment of dermatological diseases analyzing its effect at a molecular level, its signal transduction and metabolism. Presented aspects of quercetin potential for skin treatment include protection against aging and UV radiation, stimulation of wound healing, reduction in melanogenesis, and prevention of skin oxidation. The article discusses quercetin sources (plant waste products included), methods of its medical administration, and perspectives for its further use in dermatology and diet therapy.
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Quercetina , Enfermedades de la Piel , Quercetina/farmacología , Quercetina/uso terapéutico , Quercetina/química , Humanos , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/prevención & control , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Medicina Preventiva , Animales , Fitoquímicos/uso terapéutico , Fitoquímicos/química , Fitoquímicos/farmacología , Cicatrización de Heridas/efectos de los fármacosRESUMEN
The application of enzyme-based therapies has received significant attention in modern drug development. Lipases are one of the most versatile enzymes that can be used as therapeutic agents in basic skin care and medical treatment related to excessive sebum production, acne, and inflammation. The traditional formulations available for skin treatment, such as creams, ointments or gels, are widely applied; however, their use is not always accompanied by good drug penetration properties, stability, or patient adherence. Nanoformulated drugs offer the possibility of combining enzymatic and small molecule formulations, making them a new and exciting alternative in this field. In this study polymeric nanofibrous matrices made of polyvinylpyrrolidone and polylactic acid were developed, entrapping lipases from Candida rugosa and Rizomucor miehei and antibiotic compound nadifloxacin. The effect of the type of polymers and lipases were investigated, and the nanofiber formation process was optimized to provide a promising alternative in topical treatment. Our experiments have shown that entrapment by electrospinning induced two orders of magnitude increase in the specific enzyme activity of lipases. Permeability investigations indicated that all lipase-loaded nanofibrous masks were capable of delivering nadifloxacin to the human epidermis, confirming the viability of electrospinning as a formulation method for topical skin medications.
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Diabetic wounds are one of the most common health problems worldwide, enhancing the demand for new management strategies. Nanotechnology, as a developing subject in diabetic wound healing, is proving to be a promising and effective tool in treatment and care. It is, therefore, necessary to ascertain the available and distinct nanosystems and evaluate their performance when topically applied to the injury site, especially in diabetic wound healing. Several active ingredients, including bioactive ingredients, growth factors, mesenchymal stem cells, nucleic acids, and drugs, benefit from improved properties when loaded into nanosystems. Given the risk of problems associated with systemic administration, the topical application should be considered, provided stability and efficacy are assured. After nanoencapsulation, active ingredients-loaded nanosystems have been showing remarkable features of biocompatibility, healing process hastening, angiogenesis, and extracellular matrix compounds synthesis stimulation, contributing to a decrease in wound inflammation. Despite limitations, nanotechnology has attracted widespread attention in the scientific community and seems to be a valuable technological ally in the treatment and dressing of diabetic wounds. The use of nanotechnology in topical applications enables efficient delivery of the active ingredients to the specific skin site, increasing their bioavailability, stability, and half-life time, without compromising their safety.
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Diabetes Mellitus , Cicatrización de Heridas , Humanos , Piel , Diabetes Mellitus/tratamiento farmacológico , NanotecnologíaRESUMEN
Despite medical advances, skin-associated disorders continue to pose a unique challenge to physicians worldwide. Skin cancer is one of the most common forms of cancer, with more than one million new cases reported each year. Currently, surgical excision is its primary treatment; however, this can be impractical or even contradictory in certain situations. An interesting potential alternative could lie in topical treatment solutions. The goal of our study was to develop novel multilayer nanofilms consisting of a combination of polyhydroxyethyl methacrylate (PHEMA), polyhydroxypropyl methacrylate (PHPMA), sodium deoxycholate (NaDOC) with incorporated superparamagnetic iron-platinum nanoparticles (FePt NPs), and the potent anticancer drug (5-fluorouracil), for theranostic skin cancer treatment. All multilayer systems were prepared by spin-coating and characterised by atomic force microscopy, infrared spectroscopy, and contact angle measurement. The magnetic properties of the incorporated FePt NPs were evaluated using magnetisation measurement, while their size was determined using transmission electron microscopy (TEM). Drug release performance was tested in vitro, and formulation safety was evaluated on human-skin-derived fibroblasts. Finally, the efficacy for skin cancer treatment was tested on our own basal-cell carcinoma cell line.
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High-intensity focused ultrasound (HIFU) transducers are proposed as a new treatment modality for dermatology. The shape and size of pressure fields generated by strongly focused transducers with an f-number equal to 0.75 operating at frequencies up to 20 MHz are analyzed analytically using the Lucas-Muir model and numerically with the wide-angle Khokhlov-Zabolotskaya-Kuznetsov method. The modeling results under quasi-linear conditions are compared against measurements performed in an acoustic tank with the aid of a fiberoptic hydrophone. The size of the focal zone expressed by their depth of focus and focal diameter is found to be directly controlled by their operating frequency and f-number. Devices manufactured for an operating frequency of 20 MHz are characterized by their 6 dB depth of focus of 490 µm and focal diameter of 80.6 µm. The devices are further studied at high power levels using a polyacrylic tissue-mimicking phantom. The devices are equipped with an optical observation system allowing simultaneous treatment and observation of the skin surface. In comparison to conventional cosmetic applications of HIFU, the devices analyzed are concluded to be ideal for treatment of precisely selected and confined layers of the human skin.
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Ultrasonido Enfocado de Alta Intensidad de Ablación , Transductores , Acústica , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Humanos , Fantasmas de Imagen , PielRESUMEN
Objectives The current study aimed to evaluate the effectiveness of plasma skin regeneration (PSR) in the treatment of cleft lip scars in cleft lip patients. Materials and methods Twenty patients, 10 females and 10 males, with a mean age of 19 years and who had a cleft lip scar, were included in the current study. All patients were treated with a plasma skin regeneration pen device in one treatment session. The thickness, relief, and pliability of the scars were assessed by external observers using a 10-point numeric rating scale (NRS). Results The thickness, relief, and pliability of the scar were significantly improved according to the observers' opinions (51.67%, 50.25%, and 46.33%, respectively). Conclusions Within the limits of this study, the PSR appeared to be safe and effective for treating cleft lip scars with minimal complications.
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Cutaneous homeostasis can be modulated by sleep. Although there is little evidence about the efficacy of medications topically applied in the morning compared to those administered in the evening, they are commonly prescribed to be used overnight. Poor sleep may affect the tegument, but its repercussion on dermatological therapy is not clear. This communication aims to carry out an overview on the relationship between sleep and the skin, particularly in respect of the effectiveness of topical substances during the night versus the day; and the possible impact of sleep dysregulation on these treatments. Features related to this external organ, involving hydration, blood flow, and the permeability of the superficial barrier have physiological variations in sleep period. Our hypothesis is that sleep loss could alter drug absorption in the dermis and impair the success of the treatment. This can depend on the integrity of the mechanical skin barrier, and the enzymatic process after drug penetration, which may be influenced by the circadian rhythm. We raise the role of sleep disturbance in relation to skin aging and the cutaneous microbiota. The organ integrity and local immunology can be guided by sleep distress, which can modify the control of dermatological diseases. Future comparative analyses are warranted to explore the possible changes of the integumentary system influenced by circadian rhythm, and interference in response to topical dermal treatments. We emphasize the importance of sufficient sleep to improve the clinical management of several dermatosis and cosmetic complaints that need percutaneous therapeutics.
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Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Humanos , Regeneración , Piel , Sueño/fisiología , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Trastornos del Sueño-Vigilia/etiologíaRESUMEN
Matrix metalloproteinases (MMPs) are the family of proteases that are mainly responsible for degrading extracellular matrix (ECM) components. In the skin, the overexpression of MMPs as a result of ultraviolet radiation triggers an imbalance in the ECM turnover in a process called photoaging, which ultimately results in skin wrinkling and premature skin ageing. Therefore, the inhibition of different enzymes of the MMP family at a topical level could have positive implications for photoaging. Considering that the MMP catalytic region is mostly conserved across different enzymes of the MMP family, in this study we aimed to design a virtual screening (VS) workflow to identify broad-spectrum MMP inhibitors that can be used to delay the development of photoaging. Our in silico approach was validated in vitro with 20 VS hits from the Specs library that were not only structurally different from one another but also from known MMP inhibitors. In this bioactivity assay, 18 of the 20 compounds inhibit at least one of the assayed MMPs at 100 µM (with 5 of them showing around 50% inhibition in all the tested MMPs at this concentration). Finally, this VS was used to identify natural products that have the potential to act as broad-spectrum MMP inhibitors and be used as a treatment for photoaging.
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Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Metaloproteinasas de la Matriz/química , Piel/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Productos Biológicos/química , Dominio Catalítico , Pruebas de Enzimas , Ensayos Analíticos de Alto Rendimiento , Humanos , Inhibidores de la Metaloproteinasa de la Matriz/química , Metaloproteinasas de la Matriz/metabolismo , Simulación del Acoplamiento Molecular , Unión Proteica , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , Sensibilidad y Especificidad , Piel/enzimología , Piel/patología , Piel/efectos de la radiación , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Bibliotecas de Moléculas Pequeñas/química , Electricidad Estática , Relación Estructura-Actividad , Rayos Ultravioleta/efectos adversos , Interfaz Usuario-ComputadorRESUMEN
A low and stable impedance at the skin-electrode interface is key to high-fidelity acquisition of biosignals, both acutely and in the long term. However, recording quality is highly variable due to the complex nature of human skin. Here, we present an experimental and modeling framework to investigate the interfacial impedance behavior, and describe how skin interventions affect its stability over time. To illustrate this approach, we report experimental measurements on the skin-electrode impedance using pre-gelled, clinical-grade electrodes in healthy human subjects recorded over 24 h following four skin treatments: (i) mechanical abrasion, (ii) chemical exfoliation, (iii) microporation, and (iv) no treatment. In the immediate post-treatment period, mechanical abrasion yields the lowest initial impedance, whereas the other treatments provide modest improvement compared to untreated skin. After 24 h, however, the impedance becomes more uniform across all groups (<20 kΩ at 10 Hz). The impedance data are fitted with an equivalent circuit model of the complete skin-electrode interface, clearly identifying skin-level versus electrode-level contributions to the overall impedance. Using this model, we systematically investigate how time and treatment affect the impedance response, and show that removal of the superficial epidermal layers is essential to achieving a low, long-term stable interface impedance.
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Piel , Impedancia Eléctrica , Electrodos , HumanosRESUMEN
Exosomes are nano-sized cargos with a lipid bilayer structure carrying diverse biomolecules including lipids, proteins, and nucleic acids. These small vesicles are secreted by most types of cells to communicate with each other. Since exosomes circulate through bodily fluids, they can transfer information not only to local cells but also to remote cells. Therefore, exosomes are considered potential biomarkers for various treatments. Recently, studies have shown the efficacy of exosomes in skin defects such as aging, atopic dermatitis, and wounds. Also, exosomes are being studied to be used as ingredients in commercialized skin treatment products. In this review, we discussed the need for exosomes in skin therapy together with the current challenges. Moreover, the functional roles of exosomes in terms of skin treatment and regeneration are overviewed. Finally, we highlighted the major limitations and the future perspective in exosome engineering.
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The current study aims to evaluate the dependence of laser-induced optical breakdown (LIOB) on skin types by using 1064 nm picosecond laser with micro-lens arrays (MLA) and diffractive optical elements (DOE). Both black and white skin tissues were examined to comparatively assess the LIOB effects in the skin in terms of laser-induced vacuolization. The black skin irradiated at 3.0 J/cm2 demonstrated that MLA yielded a deeper distribution (180-400 µm) of laser-induced vacuoles with a size of 67 µm, compared to DOE (180-280 µm; 40 µm in size). However, the white skin presented that MLA created larger vacuoles (134 µm in size) in a smaller number at deeper distributions (125-700 µm) than MLA with the black skin. DOE generated no laser-induced vacuolization in the white skin. The white skin tissue with inherent higher scattering could be responsible for deeper vacuolization after the picosecond laser treatment. Further investigations are expected to determine the optimal treatment conditions for various skin types.
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Láseres de Estado Sólido , Lentes , Terapia por Luz de Baja Intensidad , Luz , PielRESUMEN
Pearl powder is a well-known traditional Chinese medicine for a variety of indications from beauty care to healthcare. While used for over a thousand years, there has yet to be an in-depth understanding and review in this area. The use of pearl powder is particularly growing in the biomedical area with various benefits reported due to the active ingredients within the pearl matrix itself. In this review, we focus on the emerging biomedical applications of pearl powder, touching on applications of pearl powder in wound healing, bone repairing, treatment of skin conditions, and other health indications.
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Skin, the most significant protective organ in the body, may face serious problems, including cancer, infectious diseases, etc., requiring different drugs for the treatment. However, most of these drugs have poor chemical and physical stability, and insufficient penetration through the skin layers. In recent years, with the development of nanotechnology, it has been possible to load a variety of drugs into nanocarriers, to effectively targeted drug delivery. The unique structure of niosome presents an effective novel drug delivery system with the ability to load both hydrophilic and lipophilic drugs, having many potential therapeutic applications including skin treatment. However, surveying and discussing these recent, rapidly growing reported studies, along with their theoretical principals, are required for the full understanding and exploring the great potential of this approach in skin diseases and cosmetic treatments. To this aim, an emphasis has been given to the factors affecting the penetration of niosome into the skin and their laboratory measurements and dependency on the niosome composition. In sum, longer tail surfactants for storing hydrophobic drugs and intracellular passing and surfactants with a large head group for penetrating hydrophilic drugs are more suitable. Cholesterol and oleic acid are commonly used lipids to gain more stability and permeability, respectively. The ionic component in the niosome interrupts cellular connectivity, thus making it more permeable, but it may cause relative cell toxicity. Herbal oils have been used in the structure to make the nanoparticles elastic and allow them to pass through pores without changing the size of the particles.
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Laboratorios , Liposomas , Administración Cutánea , Sistemas de Liberación de Medicamentos , PielRESUMEN
The aim of the present study was to develop innovative patches for dermo-cosmetic applications based on dissolvable hyaluronic acid (HA) microneedles (MNs) combined with bacterial nanocellulose (BC) as the back layer. HA was employed as an active biomacromolecule, with hydrating and regenerative properties and volumizing effect, whereas BC was used as support for the incorporation of an additional bioactive molecule. Rutin, a natural antioxidant, was selected as the model bioactive compound to demonstrate the effectiveness of the system. The obtained HA-MNs arrays present homogenous and regular needles, with 200 µm in base width, 450 µm in height and 500 µm tip-to-tip distance, and with sufficient mechanical force to withstand skin insertion with a failure force higher than 0.15 N per needle. The antioxidant activity of rutin was neither affected by its incorporation in the MNs system nor by their storage at room temperature for 6 months. Preliminary in vivo studies in human volunteers unveiled their safety and cutaneous compatibility, as no significant changes in barrier function, stratum corneum hydration nor redness were detected. These results confirm the potentiality of this novel system for skin applications, e.g. cosmetics, taking advantage of the recognized properties of HA and the capacity of BC to control the release of bioactive molecules.
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Sistemas de Liberación de Medicamentos , Ácido Hialurónico , Administración Cutánea , Humanos , Agujas , PielRESUMEN
BACKGROUND: Due to both intrinsic and extrinsic damage, the skin is where easily noticable signs of aging manifest. OBJECTIVE: We sought to assess the effects of two complex novel topical formulations, L'Unique Miracular Facial Serum (LMFS) and L'Unique Skin Essence (LSE) (Nourishing Biologicals LLC, St. Augustine, Florida) on hydration, firmness, elasticity, wrinkling, and pore size of facial skin after initial application and then after four, eight, and 12 weeks of use. METHODS: An open-label study was conducted on subjects (N=32) between the ages of 45 and 65 years (mean: 57 years). Subjects were treated with a twice-daily application of LMFS and LSE for a total of 12 weeks following a one-week washout period. The test products were gently applied in a circular motion to the face each morning and evening. Measurements of skin hydration, transepidermal water loss (TEWL), and skin elasticity and firmness and three-dimensional skin surface evaluations were performed at each visit. Skin lift and pore size assessments were also completed using clinical photography. Subjective outcomes were assessed by a posttreatment product efficiency survey at the end of each visit. RESULTS: Objective instrumental measurements showed statistically significant improvements in skin hydration (20.19%), TEWL (25.96% at 15 minutes), firmness (24.77%), skin elasticity (11.40%), and skin lift (5.41%) with product use. Improvements in pore size and wrinkle depth were not statistically significant. CONCLUSION: Use of the test products produced significant improvements in skin hydration, TEWL, firmness, and skin elasticity with associated improvements in facial skin appearance.
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The utilization of natural compounds, such as phenolic acids and biopolymers, in the healthcare domain is gaining increasing attention. In this study, bacterial nanocellulose (BC) membranes were loaded with ionic liquids (ILs) based on phenolic acids. These ionic compounds, with improved solubility and bioavailability, were prepared by combining the cholinium cation with anions derived from caffeic, ellagic and gallic acids. The obtained BC-ILs membranes were homogeneous, conformable and their swelling ability agreed with the solubility of each IL. These membranes revealed a controlled ILs dissolution rate in the wet state and high antioxidant activity. In vitro assays performed with Raw 264.7 macrophages and HaCaT keratinocytes revealed that these novel BC-ILs membranes are non-cytotoxic and present relevant anti-inflammatory properties. Diffusion studies with Hanson vertical diffusion cells showed a prolonged release profile of the ILs from the BC membranes. Thus, this work, successfully demonstrates the potential of BC-ILs membranes for skin treatment.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Celulosa/química , Líquidos Iónicos/farmacología , Administración Cutánea , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Antioxidantes/administración & dosificación , Antioxidantes/química , Ácidos Cafeicos/administración & dosificación , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacología , Línea Celular , Colina/administración & dosificación , Colina/química , Colina/farmacología , Liberación de Fármacos , Módulo de Elasticidad , Ácido Elágico/administración & dosificación , Ácido Elágico/química , Ácido Elágico/farmacología , Femenino , Ácido Gálico/administración & dosificación , Ácido Gálico/química , Ácido Gálico/farmacología , Humanos , Líquidos Iónicos/administración & dosificación , Líquidos Iónicos/química , Membranas Artificiales , Ratones , Nanoestructuras/química , Piel/efectos de los fármacosRESUMEN
BACKGROUND: Adhesive pads should reduce the action of the local muscle contraction on the skin leading to a decrease in the depth of existing wrinkles and the formation of new dynamic wrinkles. AIM OF THE WORK: This study aims at assessing the antiwrinkles action of adhesive pads during time, and the temporary improvement of facial skin appearance by reducing the vision of linear wrinkles and improving skin elasticity. PATIENTS AND METHODS: Thirty-nine subjects participated to a placebo-controlled study. In the short-term test, the measurements were taken 15, 30, and 60 minutes following 30 minutes application of the product; in the long-term test, the measurements were taken after wearing pads every night for 4 weeks. The roughness parameter of the skin surface was calculated by using a profilometry software 3D MEX® . RESULTS: In the short- and long-term tests, analyzing the average of the elastomeric measurements, no significant change was observed in any of the parameters analyzed after 15, 30, and 60 minutes. The adhesive pad decreased significantly all roughness skin parameters 15 minutes after short-term application and until 60 minutes after long-term application. These changes did not occur in the contralateral untreated zone. CONCLUSIONS: The use of topical adhesive pads improves wrinkles in the crow's feet area in the first hour after use. However, patient self-evaluation indicated that the use of topical adhesive pads for 3 weeks may offer subjective improvement in crow's feet zone over a 2 hour period. Topical adhesive pads are safe to use and tolerable for most users.
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Elasticidad , Envejecimiento de la Piel , Adhesivos , Adulto , Ojo , Femenino , Humanos , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Método Simple Ciego , Factores de TiempoRESUMEN
Clay minerals are layered materials with a number of peculiar properties, which find many relevant applications in various industries. Since they are easily found everywhere, they are particularly attractive due to their economic viability. In the cosmetic industry, clay minerals are often used as excipients to stabilize emulsions or suspensions and to modify the rheological behavior of these systems. They also play an important role as adsorbents or absorbents, not only in cosmetics but also in other industries, such as pharmaceuticals. This reviewer believes that since this manuscript is presented as covering topical applications that include pharmaceuticals, some types of clay minerals should be considered as a potential material to be used as drug delivery systems. We review several applications of clay minerals to dermocosmetic products, relating them to the underlying properties of these materials and exemplifying with a number of clay minerals available in the market. We also discuss the use of clay minerals in topically-applied products for therapeutic purposes, specially for skin treatment and protection.
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Silicatos de Aluminio/química , Minerales/química , Adsorción , Arcilla , Sistemas de Liberación de Medicamentos/métodos , Emulsiones/química , Excipientes/química , Humanos , Suspensiones/químicaRESUMEN
PURPOSE: The purpose of this work is to validate the Acuros BV dose calculation algorithm for high-dose-rate (HDR) brachytherapy superficial mold treatments in the absence of full scatter conditions and compare this with TG-43 dose calculations. We also investigate the impact of additional back scatter material (bolus) applied above surface molds to the dose distributions under the mold. METHODS AND MATERIALS: The absorbed dose at various depths was compared for simulations performed using either TG-43 or Acuros BV dose calculations. Parameter variations included treatment area, thickness of the bolus, and surface shape (flat or spherical). Film measurements were carried out in a flat phantom. RESULTS: Acuros BV calculations and film measurements agreed within 1.5% but were up to 15% lower than TG-43 dose calculations when no bolus was applied above the treatment catheters. The difference in dose at the prescription depth (1 cm below the central catheter) increased with increasing treatment area: 3.3% difference for a 3 × 3.5 cm2 source loading area, 7.4% for 8 × 9 cm2, and 13.4% for 18 × 19 cm2. The dose overestimation of the TG-43 model decreased when bolus was added above the treatment catheters. CONCLUSIONS: The TG-43 dosimetry formalism cannot model surface mold treatments in the absence of full scatter conditions within 5% for loading areas larger than approximately 5 × 5 cm2. The TG-43 model results in an overestimation of the delivered dose, which increases with treatment area. This confirms the need for model-based dose calculation algorithms as discussed in TG-186.