RESUMO

Wearable technologies are becoming pervasive in our society, and their development continues to accelerate the untapped potential of continuous and ubiquitous sensing, coupled with big data analysis and interpretation, has only just begun to unfold. However, existing wearable devices are still bulky (mainly due to batteries and electronics) and have suboptimal skin contact. In this work, we propose a novel approach based on a sensor network produced through inkjet printing of nanofunctional inks onto a semipermeable substrate. This network enables real-time monitoring of critical physiological parameters, including temperature, humidity, and muscle contraction. Remarkably, our system operates under battery-free and wireless near-field communication (NFC) technology for data readout via smartphones. Moreover, two of the three sensors were integrated onto a naturally adhesive bioinspired membrane. This membrane, developed using an eco-friendly, high-throughput process, draws inspiration from the remarkable adhesive properties of mussel-inspired molecules. The resulting ultra-conformable membrane adheres effortlessly to the skin, ensuring reliable and continuous data collection. The urgency of effective monitoring systems cannot be overstated, especially in the context of rising heat stroke incidents attributed to climate change and high-risk occupations. Heat stroke manifests as elevated skin temperature, lack of sweating, and seizures. Swift intervention is crucial to prevent progression to coma or fatality. Therefore, our proposed system holds immense promise for the monitoring of these parameters on the field, benefiting both the general population and high-risk workers, such as firefighters.

Assuntos

RESUMO

The development of thermosensitive bioadhesive hydrogels as multifunctional platforms for the controlled delivery of microbicides is a valuable contribution for the in situ treatment of vagina infections. In this work, novel semi-interpenetrating network (s-IPN) hydrogels were prepared by the entrapment of linear poly(methyl vinyl ether-alt-maleic anhydride) (PVME-MA) chains within crosslinked 3D structures of poly(N-isopropylacrylamide) (PNIPAAm). The multifunctional platforms were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermal techniques, rheological analysis, swelling kinetic measurements, and bioadhesion tests on porcine skin. The hydrogels exhibited an interconnected porous structure with defined boundaries. An elastic, solid-like behavior was predominant in all formulations. The swelling kinetics were strongly dependent on temperature (25 °C and 37 °C) and pH (7.4 and 4.5) conditions. The s-IPN with the highest content of PVME-MA displayed a significantly higher detachment force (0.413 ± 0.014 N) than the rest of the systems. The metronidazole loading in the s-IPN improved its bioadhesiveness. In vitro experiments showed a sustained release of the antibiotic molecules from the s-IPN up to 48 h (94%) in a medium simulating vaginal fluid, at 37 °C. The thermosensitive and bioadhesive PNIPAAm/PVME-MA systems showed a promising performance for the controlled release of metronidazole in the vaginal environment.

RESUMO

As life expectancy continues to increase, the inevitable weakening and rupture of bone tissue have grown as concerns in the medical community, thus leading to the need for adhesive materials suitable for bone repair applications. However, current commercially available adhesives face certain drawbacks that prevent proper tissue repair, such as low biocompatibility, poor adhesion to wet surfaces, and the need for high polymerization temperatures. This work aims to develop an injectable and photo-responsive chitosan methacrylate/graphene oxide (ChiMA/GO) adhesive nanocomposite hydrogel of high biocompatibility that is easy to apply by simple extrusion and that offers the possibility for in situ polymer and physiological temperatures. The nanocomposite was thoroughly characterized spectroscopically, microscopically, rheologically, thermally, and through mechanical, textural, and biological assays to fully evaluate its correct synthesis and functionalization and its performance under physiological conditions that mimic those observed in vivo. In addition, a finite element analysis (FEA) simulation was used to evaluate its performance in femur fractures. Results suggest the material's potential as a bioadhesive, as it can polymerize at room temperature, shows superior stability in physiological media, and is capable of withstanding loads from body weight and movement. Moreover, the material showed remarkable biocompatibility as evidenced by low hemolytic and intermediate platelet aggregation tendencies, and high cytocompatibility when in contact with osteoblasts. The comprehensive studies presented here strongly suggest that the developed hydrogels are promising alternatives to conventional bone adhesives that might be further tested in vivo in the near future.

RESUMO

Topical administration can enable a more efficient therapy based on the improved bioavailability and patient compliance. Wounds and infections can lead to modifications of skin physiology and body protective function. Propolis (PRP) is utilized for skin protection and treatment. However, PRP extracts do not show suitable rheological characteristics and can cause irritation, pain, ulceration, and healing difficulties when they are administered on the harmed skin. Emulgels composed of Carbopol 934P (C934P) and different vegetable oils have been proposed for propolis extract release and may be a good strategy for topical delivery. The aim of this study was to investigate the bioadhesive properties, PRP release profile, skin permeation, and retention, by Franz's diffusion cell and photoacoustic spectroscopy (PS), of these emulgels. Formulations were composed of C934P and passion fruit oil (PF), sweet almond oil (SA), or andiroba oil (AO). PRP or by-product extracts were added to the systems, drug release profile was investigated, and porcine ear skin was utilized for analyses of bioadhesive properties, skin permeation, and retention. All formulations displayed similar bioadhesive force (0.05-0.07 N); PRP release was modified (prolonged), dependent on formulation composition, and mainly governed by diffusion. PS and analysis using diffusion cell showed that the systems could provide dermal permeation and retention, which was more effective for formulations containing AO. Considering the importance of propolis for many skin therapies, the emulgels containing AO for PRP delivery are worthy of biological studies and further clinical evaluation.

Assuntos

RESUMO

OBJECTIVE: The aim of the present study was to evaluate the influence of the incorporation of caffeine as a model active ingredient on the quality attributes of a bioadhesive emulgel formulation previously optimized by Quality by Design (QbD) tools. Emulgels are emerging topical drug delivery systems for cosmetic or pharmaceutical uses, which combine the advantages of both emulsions and gels. METHODS: In this work, the observed and predicted values for spreadability, phase separation by centrifugation and detachment forces performed by texturometer were compared with those of the control and active-containing emulgel formulations. In addition, rheological properties, release of caffeine and comparative in vitro/ex vivo bioadhesion properties were evaluated using human skin. RESULTS: The flow curves of emulgel formulations showed the typical pseudoplastic and no thixotropic flow with yield stress. The incorporation of active ingredient did not produce significant changes. All emulgels were uniformly spread and no significant differences in spreadability values between control and caffeine containing formulations and neither respect to those predicted values from experimental design optimization were found. Emulgel formulations showed appropriate detachment forces values and no significant differences between caffeine loading and control emulgel formulations were observed. CONCLUSION: Caffeine was successfully vehiculized in this optimized bioadhesive emulgel formulation, which showed high robustness regarding the process variability. There were no significant changes in the critical quality attributes after the incorporation of the active ingredient and a promising stability was observed for at least one year. Results suggested that the optimized emulgel is an interesting topical biodhesive delivery system for cosmetic applications, including agents for skin conditioning, not present in gels formulations.

OBJECTIF: la présente étude visait à évaluer l'influence de l'incorporation de la caféine comme une substance active modèle dans les attributs de qualité d'une préparation d'émulgel bioadhésif préalablement optimisée grâce à des outils QbD (Quality by Design, Qualité par la conception). Les émulgels sont des systèmes d'administration de médicaments topiques émergents destinés à des usages cosmétiques ou pharmaceutiques, qui associent les avantages des émulsions et des gels. MÉTHODES: dans cet étude, les valeurs observées et prédites en matière d'étalement, de séparation des phases par centrifugation et de forces de détachement par texturomètre ont été comparées à celles des préparations de contrôle et d'émulgel contenant des actifs. En outre, les propriétés rhéologiques, la libération de caféine et la comparaison des propriétés de bioadhérence in vitro / ex vivo ont été évaluées sur la peau humaine. RÉSULTATS: les courbes de débit des préparations d'émulgel révèlent un flux pseudoplastique typique et non thixotropique avec charge d'écoulement. L'incorporation de la substance active n'a pas produit de changements importants. Tous les émulgels ont été uniformément étalés et aucune différence significative dans les valeurs d'étalement entre les préparations de contrôle et celles contenant de la caféine n'a été observée. Aucune différence concernant les valeurs prédites dans l'optimisation de la conception expérimentale n'a été observée. Les préparations d'émulgel ont montré des valeurs de forces de détachement appropriées et aucune différence significative n'a été observée entre les préparations d'émulgel à base de caféine et les préparations de contrôle. CONCLUSION: la caféine a été administrée avec succès dans cette préparation optimisée d'émulgel bioadhésif, qui a affiché une grande résistance en ce qui concerne la variabilité du procédé. Il n'y a pas eu de changement significatif dans les attributs de qualité critiques après l'incorporation de la substance active et une stabilité prometteuse a été observée pendant au moins un an. Les résultats ont suggéré que l'émulgel optimisé est un système d'administration de bioadhérence topique intéressant pour les applications cosmétiques, y compris les agents de revitalisation de la peau qui ne se trouvent pas dans les préparations de gels.

Assuntos

RESUMO

Objetivo: Desarrollar una nueva técnica para la transferencia de cianometacrilato de muy baja densidad sobre las superficies internas y externas del corazón. Material y métodos: Se combinó el cianometacrilato curado por luz ultravioleta de muy baja densidad con colorante comercial para demostrar su capacidad de transferencia sobre las superficies externas e internas de un modelo de corazón in vitro. Se mezclaron 0,5 ml de cianometacrilato con 0,2 ml tinta, y el material se inyectó sobre la superficie del corazón en aire seco, lo que permite su fijación durante 2-3 seg. A continuación, toda la preparación se sumergió en solución salina y se agitó vigorosamente para eliminar el compuesto no ligado. Se realizó un experimento similar sin cianometacrilato y con cianometacrilato de alta viscosidad (3000 cps). Se comprobó visualmente después del lavado que una cantidad significativa del compuesto se liga a las superficies del corazón en comparación con la tinta sola. Luego, se investigó la transferencia efectiva del compuesto a las superficies internas y externas del corazón después de haber sumergido el tejido en solución salina. Entre diversas técnicas, la de pincelado fue la más efectiva para la transferencia orientada del compuesto. Mediante esta técnica fue muy fácil transferir el compuesto sobre las superficies endocárdica y epicárdica. También otras áreas específicas, como la orejuela auricular izquierda, las superficies internas del ventrículo izquierdo en el origen del músculo papilar y el ápex ventricular izquierdo, fueron investigadas exitosamente. La fuente de luz ultravioleta fue un dispositivo en forma de lapicera basado en un diodo emisor de luz. Luego del tratamiento con luz ultravioleta, se observó cierta precipitación del compuesto en algunas zonas. El experimento se repitió con tres muestras para determinar el resultado. Conclusiones: La transferencia de cianometacrilato de muy baja viscosidad curado por luz ultravioleta es potencialmente útil para el estudio de las superficies internas y externas del corazón. Esta técnica podría servir para la transferencia de factor de crecimiento.

Background: Cyan methacrylate is a compound with remarkable adhesion properties used in different specific areas, including medicine, where it can be applied in some entities and is also subject of research in the field of cardiology Objective: The aim of this study was to develop a novel technique for the transfer of very-low viscosity cyan methacrylate on the inner and outer surfaces of the heart. Methods: Very-low viscosity ultraviolet curable cyan methacrylate was mixed with commercially available dye to demonstrate its ability of transfer on the inner and outer surfaces of an in-vitro heart model. Cyan methacrylate (0.5 ml) was mixed with 0.2 ml of ink, and the material was injected on the surface of the heart in dry air, allowing its fixation for 2-3 seconds. Subsequently, the whole preparation was immersed in saline, and was vigorously shaken to remove the unbound compound. A similar experi-ment was performed without cyan methacrylate, and with high viscosity cyan methacrylate (3000 cps). A significant amount of the compound was visually found to attach to the surfaces of the heart compared with ink alone. Then, after soaking the tissue in saline solution, effective transfer of the compound was assessed on the inner and the outer surfaces of the heart. Results: Among various techniques, the paintbrush technique was the most effective one for the targeted transfer of the com-pound. With this specific areas, such as instead of specific areas, as technique, it was easier to transfer the compound on the epicardial and endocardial surfaces. Also, other specific areas, as the left atrial appendage, the left ventricular inner surfaces at the origin of the papillary muscle and the left ventricular apex were successfully investigated. The ultraviolet light source was a pen-shaped device based on a light emission diode. Some compound precipitation was observed in some areas following ultraviolet treatment. The experiment was repeated with three different samples to determine the results. Conclusions: Very-low viscosity ultraviolet curable cyan methacrylate transfer is potentially useful to study the inner and outer surfaces of the heart. This technique could be useful for growth factor transfer.

RESUMO

Dental caries, mainly caused by the adhesion of Streptococcus mutans to pellicle-coated tooth surfaces, is an important public health problem worldwide. A synthetic peptide (p1025) corresponding to residues 1025-1044 of the adhesin can inhibit this binding. Peptides are particularly susceptible to the biological environment; therefore, a p1025 peptide-loaded liquid crystalline system (LCS) consisting of tea tree oil as the oil phase, polyoxypropylene-(5)-polyoxyethylene-(20)-cetyl alcohol as the surfactant, and water or 0.5% polycarbophil polymer dispersions as the aqueous phase was employed as a drug delivery platform. This system exhibited anticaries and bioadhesive properties and provided a protective environment to p1025 at the site of action, thereby modulating its action, prolonging its contact with the teeth, and decreasing the frequency of administration. LCSs were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), and rheological, texture, and bioadhesive tests. PLM and SAXS revealed the presence of hexagonal liquid crystalline phases and microemulsions. Rheological analyses demonstrated that the addition of polymer dispersions favored characteristics such as shear thinning and thixotropy, hence improving buccal application. Bioadhesion tests showed that polymer dispersions contributed to the adhesion onto the teeth. Taken together, LCS could provide a novel pharmaceutical nanotechnology platform for dental caries treatment.

Assuntos

RESUMO

Se desarrollaron sistemas poliméricos bioadhesivos del tipo película polimérica y comprimido empleando el biopolímero pullulan, para el transporte de digluconato de clorhexidina, el cual es un principio activo utilizado como alternativa terapéutica en el tratamiento de la gingivitis y de la enfermedad periodontal. Inicialmente, se evaluó la capacidad del polímero para formar películas y tabletas, luego, fueron propuestas formulaciones de cada uno de los sistemas. A las películas y comprimidos obtenidos se les determinaron propiedades mecánicas y de transporte, actividad antiséptica, caracterización de las microestructuras obtenidas, además, se comprobó la liberación del fármaco desde los sistemas estudiados. Con las formulaciones seleccionadas se determinó su capacidad mucoadhesiva in vitro, empleando como sustrato mucosa oral porcina.

As a therapeutic alternative in the transport of active substances in treatment of gingivitis and periodontal disease, bioadhesive polymeric systems type polymeric film and tablet were developed using the biopolymer pullulan. First, the ability of pullulan polymer to form films and tablets was evaluated and formulations were proposed for each system. Mechanical and transport properties, as well as antiseptic activity and microstructures characteristics were determined for these polymeric systems. Drug release behavior in the studied systems was also verified. The in vitro mucoadhesive capacity was determined with the formulations selected, using porcine oral mucous membrane like substrate.

RESUMO

We evaluated the histological dental pulp state in vivo after indirect pulp capping using sildenafil or LG-nitro-L-arginine (L-NAME), incorporated into a new bioadhesive thermoresponsive system (BTS). Male Wistar rats were subjected to an upper and lower first molar class I cavity preparation followed by indirect pulp capping with sildenafil or L-NAME. Calcium hydroxide (CaOH2) was used as a control. The teeth and surrounding bone were properly dissected and processed for Nissl's staining. Pulp state was evaluated considering the morphological aspects of the inflammatory response, type of inflammatory infiltrate, organization of the odontoblast layer, blood vessel condition, and presence of abscesses or necrosis. The results were expressed as average of observations. The most intense inflammatory response was observed 3 days after the cavity preparation. No identified changes were detected in the dental pulp response of the molars treated with L-NAME compared with those treated with CaOH2. A dual effect was observed in the teeth treated with sildenafil. While low sildenafil concentration (0.015% w w-1) promoted effects comparable to CaOH2, at a higher concentration (0.15% w w-1), sildenafil caused a severe inflammatory response and pulp necrosis. This pioneering suggest that NO pathway activity may be a determinant in the process of dental pulp healing.

Avaliou-se o estado histológico da polpa dental in vivo após capeamento pulpar indireto usando sildenafil ou LG-nitro-L-arginine (L-NAME), incorporados num novo sistema bioadesivo termorresponsivo (BTS). Ratos Wistar machos foram sujeitos ao preparo cavitário, classe I nos primeiros molares superiores e inferiores, seguido de capeamento pulpar indireto com sildenafil ou L-NAME incorporados em BTS. Hidróxido de cálcio (CaOH2) foi usado como controle positivo. Os dentes e tecidos adjacentes foram adequadamente dissecados e processados para a coloração de Nissl. O estado da polpa foi avaliado quanto aos aspectos morfológicos e tipo do infiltrado inflamatório, organização da camada de odontoblastos, condições dos vasos sanguíneos e presença de abcesso ou necrose. A reposta inflamatória mais intensa foi observada três dias após o preparo cavitário. Nenhuma alteração foi detectada na polpa dental dos molares tratados com L-NAME comparados com aqueles tratados com CaOH2. Um efeito dual foi observado nos dentes tratados com sildenafil. Enquanto baixas concentrações de sildenafil (0.015% v v-1) promoveram efeitos comparáveis com o CaOH2, altas concentrações (0.15% v v-1) causaram uma severa resposta inflamatória e necrose pulpar. Este estudo pioneiro sugere que a atividade da via do NO pode ser determinante no processo de cicatrização.

Assuntos

RESUMO

INTRODUCTION: The use of bioadhesive hydrogels for skin care presents important advantages such as long residence times on the application site and reduced product administration frequency. OBJECT: The aim of the present work was to develop bioadhesive hydrogels for skin application, using caffeine as a model active ingredient. METHODS: Eight hydrogels were formulated using binary combinations of a primary polymer (carbomer homopolymer type C (Carbopol(®) 980) or kappa carrageenan potassium salt (Gelcarin(®) GP-812 NF)) and a secondary polymer (carbomer copolymer type B (Pemulen(™) TR-1), xanthan gum or guar gum). Hydrogels were characterized by means of physico-chemical (dynamic rheological measurements, spreadability and adhesion measurements) and sensory methods (projective mapping in combination with a check-all-that-apply (CATA) question). Caffeine hydrogels were formulated using two of the most promising formulations regarding adhesion properties and sensory characteristics. In vitro active ingredient release studies were carried out. RESULTS: Hydrogel formulations showed a prevalently elastic rheological behaviour. Complex viscosity of carbomer homopolymer type C hydrogels was higher than that of the kappa carrageenan hydrogels. Besides, complex viscosity values were dependent on the secondary polymer present in the formulation. Significant differences among hydrogels were found in detachment force, work of adhesion and spreading diameter results. Association of projective mapping with CATA allowed to determine similarities and dissimilarities among samples. Cluster analysis associated the samples in two groups. Two hydrogels were selected to study the release of caffeine. Both hydrogels presented similar release profiles which were well described by the Higuchi model. Caffeine release was exclusively controlled by a diffusive process. CONCLUSION: Physico-chemical and sensory techniques enabled the identification of bioadhesive hydrogel formulations with positive characteristics for cosmetic applications. Formulations which combined carbomer homopolymer type C with xanthan gum or with carbomer copolymer type B were the most promising for bioadhesive skin products. Caffeine release profiles of selected formulations were not statistically different. Both hydrogels gradually released the active ingredient, reaching approximately 80% within the first 5 h, and their profiles were well described by the Higuchi model. In this context, it could be concluded that the selected hydrogels are suitable bioadhesive hydrogel formulations for cosmetic application on the skin.

Assuntos

RESUMO

New hyaluronic acid (HA)-itaconic acid (IT) films have been previously synthesized and used as potential topical drug delivery systems (DDS) for ocular administration. In this study we explored homogeneous and heterogeneous crosslinking reactions of HA using glutaraldehyde (GTA) and polyethylene glycol diglycidyl ether (PEGDE) in the presence of IT, a naturally occurring compound that is non-toxic and readily biodegradable. We have studied the morphology, mechanical properties and in vitro biocompatibility between these new materials and ocular surface cells (human corneal epithelial cell line) and evaluated the biopharmaceutical performance of the designed formulations. Although all the synthesized materials exhibited good mechanical properties, the PEGDE modified films exhibited the best biocompatibility, with in vivo assays showing good adhesive performance and minimal irritation. PEGDE films were also tested for their effects in the treatment of intraocular pressure (IOP) in rabbits using timolol maleate (TM) as the model drug. These results may be useful for further design of novel bioadhesive matrix containing drugs by topical application in ophthalmology.

Assuntos

RESUMO

The purpose of this study was formulation and in vitro evaluation of floating-bioadhesive tablets to lengthen the stay of glipizide in its absorption area. Effervescent tablets were made using chitosan (CH), hydroxypropyl methylcellulose (HPMC), carbopolP934 (CP), polymethacrylic acid (PMA), citric acid, and sodium bicarbonate. Tablets with 5 percent effervescent base had longer lag time than 10 percent. The type of polymer had no significant effect on the floating lag time. All tablets floated atop the medium for 23-24 hr. Increasing carbopolP934 caused higher bioadhesion than chitosan (p < 0.05). All formulations showed a Higuchi, non-Fickian release mechanism. Tablets with 10 percent effervescent base, 80 percent CH/20 percent HPMC, or 80 percent CP/20 percent PMA seemed desirable.