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Multicellular cyanobacteria, like Nostoc punctiforme, rely on septal junctions for cell-cell communication, which is crucial for coordinating various physiological processes including differentiation of N2-fixing heterocysts, spore-like akinetes, and hormogonia-short, motile filaments important for dispersal. In this study, we functionally characterize a protein, encoded by gene Npun_F4142, which in a random mutagenesis approach, initially showed a motility-related function. The reconstructed Npun_F4142 knockout mutant exhibits further distinct phenotypic traits, including altered hormogonia formation with significant reduced motility, inability to differentiate heterocysts and filament fragmentation. For that reason, we named the protein FraI (fragmentation phenotype). The mutant displays severely impaired cell-cell communication, due to almost complete absence of the nanopore array in the septal cell wall, which is an essential part of the septal junctions. Despite lack of communication, hormogonia in the ΔfraI mutant maintain motility and phototactic behavior, even though less pronounced than the wild type (WT). This suggests an alternative mechanism for coordinated movement beyond septal junctions. Our study underscores the significance of FraI in nanopore formation and cell differentiation, and provides additional evidence for the importance of septal junction formation and communication in various differentiation traits of cyanobacteria. The findings contribute to a deeper understanding of the regulatory networks governing multicellular cyanobacterial behavior, with implications for broader insights into microbial multicellularity. IMPORTANCE: The filament-forming cyanobacterium Nostoc punctiforme serves as a valuable model for studying cell differentiation, including the formation of nitrogen-fixing heterocysts and hormogonia. Hormogonia filaments play a crucial role in dispersal and plant colonization, providing a nitrogen source through atmospheric nitrogen fixation, thus holding promise for fertilizer-free agriculture. The coordination among the hormogonia cells enabling uniform movement toward the positive signal remains poorly understood. This study investigates the role of septal junction-mediated communication in hormogonia differentiation and motility, by studying a ΔfraI mutant with significantly impaired communication. Surprisingly, impaired communication does not abolish synchronized filament movement, suggesting an alternative coordination mechanism. These findings deepen our understanding of cyanobacterial biology and have broader implications for multicellular behavior in prokaryotes.
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BACKGROUND: Evidence on the health benefits of spending time in nature has highlighted the importance of provision of blue and green spaces where people live. The potential for health benefits offered by nature exposure, however, extends beyond health promotion to health treatment. Social prescribing links people with health or social care needs to community-based, non-clinical health and social care interventions to improve health and wellbeing. Nature-based social prescribing (NBSP) is a variant that uses the health-promoting benefits of activities carried out in natural environments, such as gardening and walking. Much current NBSP practice has been developed in the UK, and there is increasing global interest in its implementation. This requires interventions to be adapted for different contexts, considering the needs of populations and the structure of healthcare systems. METHODS: This paper presents results from an expert group participatory workshop involving 29 practitioners, researchers, and policymakers from the UK and Germany's health and environmental sectors. Using the UK and Germany, two countries with different healthcare systems and in different developmental stages of NBSP practice, as case studies, we analysed opportunities, challenges, and facilitators for the development and implementation of NBSP. RESULTS: We identified five overarching themes for developing, implementing, and evaluating NBSP: Capacity Building; Accessibility and Acceptability; Networks and Collaborations; Standardised Implementation and Evaluation; and Sustainability. We also discuss key strengths, weaknesses, opportunities, and threats for each overarching theme to understand how they could be developed to support NBSP implementation. CONCLUSIONS: NBSP could offer significant public health benefits using available blue and green spaces. We offer guidance on how NBSP implementation, from wider policy support to the design and evaluation of individual programmes, could be adapted to different contexts. This research could help inform the development and evaluation of NBSP programmes to support planetary health from local and global scales.
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Dormancy and resuscitation are key to bacterial survival under fluctuating environmental conditions. In the absence of combined nitrogen sources, the non-diazotrophic model cyanobacterium Synechocystis sp. PCC 6803 enters into a metabolically quiescent state during a process termed chlorosis. This state enables the cells to survive until nitrogen sources reappear, whereupon the cells resuscitate in a process that follows a highly orchestrated program. This coincides with a metabolic switch into a heterotrophic-like mode where glycogen catabolism provides the cells with reductant and carbon skeletons for the anabolic reactions that serve to re-establish a photosynthetically active cell. Here we show that the entire resuscitation process requires the presence of sodium, a ubiquitous cation that has a broad impact on bacterial physiology. The requirement for sodium in resuscitating cells persists even at elevated CO2 levels, a condition that, by contrast, relieves the requirement for sodium ions in vegetative cells. Using a multi-pronged approach, including the first metabolome analysis of Synechocystis cells resuscitating from chlorosis, we reveal the involvement of sodium at multiple levels. Not only does sodium play a role in the bioenergetics of chlorotic cells, as previously shown, but it is also involved in nitrogen compound assimilation, pH regulation, and synthesis of key metabolites.
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Nature experiences usually lead to restorative effects, such as positive affective states and reduced stress. Even watching nature compared to urban images, which are known to differ in several image properties that are processed at early stages, can lead to such effects. One potential pathway explaining how the visual input alone evokes restoration is that image properties processed at early stages in the visual system evoke positive associations. To study these automatic bottom-up processes and the role of lower-level visual processing involved in the restoring effects of nature, we conducted two studies. First, we analyzed nature and urban stimuli for a comprehensive set of image properties. Second, we investigated implicit associations in a dichotomous set of nature and urban images in three domains, namely, valence, mood, and stress restoration. To examine the role of lower-level processing in these associations, we also used stimuli that lacked the spatial information but retained certain image properties of the original photographs (i.e., phase-scrambled images). While original nature images were associated with "good," "positive mood," and "restoration," urban images were associated with "bad" and "stress." The results also showed that image properties differ between our nature and urban images and that they contribute to the implicit associations with valence, although spatial information and therefore recognition of the environment remained necessary for positive associations. Moreover, lower-level processed image properties seem to play no or only minor roles for associations with mood and stress restoration.
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Natural environments, compared to urban environments, usually lead to reduced stress and positive body appreciation. We assumed that walks through nature and urban environments affect self- and other-perceived stress and attractiveness levels. Therefore, we collected questionnaire data and took photographs of male participants' faces before and after they took walks. In a second step, female participants rated the photographs. As expected, participants felt more restored and attractive, and less stressed after they walked in nature compared to an urban environment. A significant interaction of environment (nature, urban) and time (pre, post) indicated that the men were rated by the women as being more stressed after the urban walk. Other-rated attractiveness levels, however, were similar for both walks and time points. In sum, we showed that the rather stressful experience of a short-term urban walk mirrors in the face of men and is detectable by women.
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Emociones , Ambiente , Estrés Psicológico , Caminata , Imagen Corporal , Ciudades , Femenino , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
While the virus SARS-CoV-2 spreads all over the world, most countries have taken severe measures to protect their citizens and slow down the further spread of the disease COVID-19. These measures affect individuals, communities, cities, countries, and the entire planet. In this paper, we propose that the tremendous consequences of the corona crisis invite environmental psychology to focus more strongly on research questions that address major societal challenges from a collective psychology perspective. In particular, we stress that the corona crisis may affect how people appraise - and potentially respond to - the looming climate crisis. By consistently pointing out systemic links and their human factor, environmental psychology can become central to a scientific agenda of a sustainable 'post-corona society'. In order to provide a framework for future research towards a sustainable societal transformation, we build on the Social Identity Model of Pro-Environmental Action (SIMPEA) and extend its scope to understand people's responses following the corona crisis. The model allows predictions of previously not explicitly included concepts of place attachment, nature connectedness, basic psychological needs, and systems thinking. It may serve as a guiding framework for a better understanding of the transformation towards a sustainable future.
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The aim of this study was to develop a novel mucoadhesive cationic polymer by introducing primary amino groups to the polymeric backbone of starch. This newly synthesized polymer should exhibit superior properties over chitosan regarding solubility, mucoadhesiveness and cytotoxicity. Increasing amounts of sodium periodate were used to cleave and oxidize vicinal diols under aldehyde formation obtaining three different degrees of modification. In a subsequent step, primary amines were introduced via reductive amination with ammonia. Degree of amination was examined with TNBS-assay and zeta potential measurements. Mucoadhesiveness was investigated by rotating cylinder, tensile studies and rheological measurements. Primary amino groups were successfully attached to the polymer, proven by zeta potential measurements and UV-spectroscopy. Depending on the amount of periodate used in the reaction, coupling rates of up to 514⯵mol/g polymer were achieved. All synthesized derivatives showed 100% solubility in a pH range of 1-9. Aminated starch with the highest coupling rate of 514⯵mol/g showed a 9.5-fold prolonged retention time on intestinal mucosa and a 2.7-fold higher total work of adhesion on the mucosal tissue compared to chitosan. Furthermore, cytotoxic examinations of all tested polymers showed only a low impact on cell viability after 24â¯h, whereby starch derivatives possessed even less cell toxic effects than chitosan. Summarizing these results, cationic starch derivatives seem to be promising excipients for mucosal drug delivery with superior properties compared to chitosan, the most examined cationic polymer.
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Adhesivos/química , Cationes/química , Excipientes/química , Almidón/química , Adhesividad , Células CACO-2 , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Quitosano/química , Sistemas de Liberación de Medicamentos/métodos , Humanos , Mucosa Intestinal/efectos de los fármacos , Polímeros/química , Reología , Solubilidad/efectos de los fármacosRESUMEN
The excessive production and consumption of plastic has serious consequences on the environment and human health. The reduction of plastic has therefore become a major global challenge. As technical solutions might be insufficient to curb the problem, a perspective highlighting the impact of human behavior is needed. The current literature review provides an overview of the existing social-scientific literature on plastic, ranging from risk awareness, consumers' preferences, and predictors of usage behavior to political and psychological intervention strategies. By reviewing the literature, we aim to identify potential factors for future interventions to reduce plastic consumption. The 187 studies reviewed show that people much appreciate and routinely use plastic, despite a pronounced awareness of the associated problems. Habits, norms, and situational factors seem to be especially predictive for plastic consumption behavior. Both political and psychological interventions are potentially effective, although long-term effects are often uncertain. The review closes with implications for behavior-based solutions and future research, which should combine interdisciplinary approaches and take into account cultural differences.
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AIM: The aim of the study was to establish a novel type of covalently mucus-binding polymers by targeting selectively amino groups within mucus glycoproteins. METHODS: N-Hydroxysuccinimide (NHS) was attached to carboxylic groups of polyacrylic acid (PAA). The reaction was mediated by the coupling reagent N,N'-dicyclohexylcarbodiimide (DCC) achieving polymeric NHS esters being able to form amide bonds with free amino groups. The chemical structure of the obtained conjugates was characterized via FTIR- and UV spectroscopy. Reactivity towards mucosal amino groups was evaluated UV spectrometrically upon addition of L-glycine. Furthermore, tensile force evaluations on intestinal mucosa as well as rheological experiments with mucus were performed in order to prove mucoadhesive potential. RESULTS: Depending on the amount of NHS added to the synthesis, coupling rates of 876 to 1820⯵mol NHS per gram polymer were obtained. Kinetic studies of amide bond formation showed a substrate dependent reaction velocity. Rheological synergism of PAA-NHS was proven by a 7.9-fold increased mucus viscosity compared to the control polymer. In further mucoadhesion studies PAA-NHS showed a 5.5-fold improved adhesion time compared to unmodified PAA. Tensile force evaluation confirmed these results with a 1.7-fold higher maximum detachment force (MDF) and 2.7-fold increased total work adhesion (TWA) for PAA-NHS compared to the unmodified control polymer. CONCLUSION: The results of the present study provide strong evidence that coupling NHS to polymers could be a promising tool for the development of novel mucoadhesive excipients.
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Resinas Acrílicas/química , Sistemas de Liberación de Medicamentos/métodos , Excipientes/química , Succinimidas/química , Adhesividad , Células CACO-2 , Química Farmacéutica , Humanos , Mucosa Intestinal/metabolismo , ReologíaRESUMEN
The objective of the study was to compare poly(acrylic acid)- N-hydroxysulfosuccinimide reactive esters (PAA-Sulfo-NHS) and poly(acrylic acid)-cysteine conjugates (PAA-Cys) regarding their mucoadhesiveness. Polymer conjugates were synthesized in a water free environment and characterized by UV-vis spectroscopy and FTIR. Water uptake studies were performed, and the polymers were further examined for their mucoadhesive properties and cohesiveness using the rotating cylinder method. Tensile force measurements were conducted to define the strength of adhesion to porcine intestinal mucosa. Additionally, polymer-mucus mixtures were assessed for rheological synergism by measuring the increase in dynamic viscosity. Both modifications led to a prolonged adhesion time compared to unmodified PAA. Fast dissolution of PAA-Sulfo-NHS derivatives was monitored, whereas PAA-Cys tended to extensively swell while exhibiting high cohesive properties. Measurements of tensile force revealed up to 2.7-fold (PAA-Sulfo-NHS) and 2.3-fold (PAA-Cys) enhancement of the maximum detachment force and 7.6-fold (PAA-Sulfo-NHS) and 3.6-fold (PAA-Cys) increase in the total work of adhesion. Formation of a gel network between polymer and mucus was confirmed by a 10.8-fold (PAA-Sulfo-NHS) and 20.8-fold (PAA-Cys) increase in viscosity. Both types of polymers show high mucoadhesive properties due to the formation of covalent bonds with the mucus. As thiolated polymers are capable of forming stabilizing disulfide bonds within their polymeric network, they are advantageous over PAA-Sulfo-NHS.
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Resinas Acrílicas/química , Cisteína/análogos & derivados , Ésteres/química , Mucosa Intestinal/química , Succinimidas/química , Adhesividad , Animales , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Cisteína/síntesis química , Cisteína/química , Sistemas de Liberación de Medicamentos , Estabilidad de Medicamentos , Sinergismo Farmacológico , Ésteres/síntesis química , Hemólisis/efectos de los fármacos , Humanos , Hidrólisis , Moco/fisiología , Porcinos , Resistencia a la Tracción , ViscosidadRESUMEN
The aim of this study was the synthesis and in vitro characterization of aminated cellulose as alternative excipient to chitosan. The aldehyde form of cellulose was generated via the oxidative cleavage of vicinal diols by the addition of increasing concentrations of sodium periodate. The insertion of primary amines was achieved by reductive amination with ammonia. The degree of substitution was calculated via primary amino group quantification using a 2,4,6-trinitrobenzenesulfonic acid assay. Mucoadhesiveness was examined by adopting the rotating-cylinder method and tensile studies using porcine intestinal mucosa. Hydration was evaluated at pH 2-11. The successful formation of aldehydes as well as a subsequent introduction of up to 311.61 micromoles per gram of primary amines were proven to correlate with the amount of added periodate. There was a 3- to 14-fold prolongation in the mucosal residence time of the new polymer in comparison to chitosan, as measured by the rotating-cylinder method. Although cationic cellulose did not reach the maximum detachment force of chitosan, the total work of adhesion of the newly synthesized cellulose derivate was higher than that of chitosan. The higher the degree of amination, the higher the degree of hydration in neutral and alkaline aqueous media was. Compared to chitosan, the novel cationic cellulose derivative displays improved mucoadhesive properties as well as sufficient hydration at physiological pH. Therefore, aminated cellulose is a promising alternative to the cationic polymers, such as chitosan, used thus far.
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Celulosa/química , Quitosano/química , Excipientes , Mucosa Intestinal/fisiología , Polímeros/química , Adhesividad , Aminación , Animales , Células CACO-2 , Supervivencia Celular , Células HEK293 , Humanos , Porcinos , Resistencia a la TracciónRESUMEN
Most recent studies in experimental aesthetics have focused on the cognitive processing of visual artworks. In contrast, the perception of formal compositional features of artworks has been studied less extensively. Here, we investigated whether fast and automatic processing of artistic image composition can lead to a stable and consistent aesthetic evaluation when cognitive processing is minimized or absent. To this aim, we compared aesthetic ratings on abstract artworks and their shuffled counterparts in a gist experiment. Results show that exposure times as short as 50 ms suffice for the participants to reach a stable and consistent rating on how ordered and harmonious the abstract stimuli were. Moreover, the rating scores for the 50 ms exposure time exhibited similar dependencies on image type and self-similarity and a similar pattern of correlations between different rating terms, as the rating scores for the long exposure time (3,000 ms). Ratings were less consistent for the term interesting and inconsistent for the term pleasing. Our results are compatible with a model of aesthetic experience, in which the early perceptual processing of the formal aspects of visual artworks can lead to a consistent aesthetic judgment, even if there is no cognitive contribution to this judgment.
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We studied low-level image properties of face photographs and analyzed whether they change with different emotional expressions displayed by an individual. Differences in image properties were measured in three databases that depicted a total of 167 individuals. Face images were used either in their original form, cut to a standard format or superimposed with a mask. Image properties analyzed were: brightness, redness, yellowness, contrast, spectral slope, overall power and relative power in low, medium and high spatial frequencies. Results showed that image properties differed significantly between expressions within each individual image set. Further, specific facial expressions corresponded to patterns of image properties that were consistent across all three databases. In order to experimentally validate our findings, we equalized the luminance histograms and spectral slopes of three images from a given individual who showed two expressions. Participants were significantly slower in matching the expression in an equalized compared to an original image triad. Thus, existing differences in these image properties (i.e., spectral slope, brightness or contrast) facilitate emotion detection in particular sets of face images.
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Reconocimiento Facial , Fotograbar , Adulto , Emociones , Expresión Facial , Femenino , Humanos , MasculinoRESUMEN
The aim of this study was to develop a self-emulsifying drug delivery system (SEDDS) containing the fluoroquinolone antibiotic ciprofloxacin (CIP) exhibiting highly mucus permeating properties and antimicrobial activity in in vitro models. Various SEDDS formulations were developed and evaluated regarding droplet size, polydispersity index, zeta potential and formulation stability. Furthermore, SEDDS permeating properties were investigated in porcine intestinal mucus, as well as in cystic fibrosis (CF) sputum freshly collected from CF patients using Transwell® setup and single particle tracking (SPT), respectively. In order to evaluate antibacterial activity in an in vitro model against Staphylococcus aureus and other pathogens, minimum inhibitory concentrations (MIC) and time-kill curves were determined. In addition, in vitro release of ciprofloxacin and cytotoxicity studies were conducted. The preselected formulations F1 and F11 exhibited a mean droplet size of 79â¯nm and 25â¯nm, respectively, and a negative zeta potential. SEDDS containing CIP exhibit improved ability to permeate porcine intestinal mucus and CF sputum. After 4â¯h, F1-CIP formulation resulted in a 1.6 - fold and F11-CIP a 2.0 - fold higher amount of permeated ciprofloxacin through the sputum layer with respect to free CIP. Moreover, the antimicrobial activity of F11-CIP against S. aureus was higher than that of free CIP. According to these results, SEDDS formulations should be taken into consideration as promising delivery systems for the treatment of pulmonary infections accompanied by mucus dysfunction.
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Antibacterianos/administración & dosificación , Ciprofloxacina/administración & dosificación , Sistemas de Liberación de Medicamentos , Staphylococcus aureus/efectos de los fármacos , Animales , Antibacterianos/farmacocinética , Química Farmacéutica/métodos , Ciprofloxacina/farmacocinética , Fibrosis Quística/metabolismo , Estabilidad de Medicamentos , Emulsiones , Humanos , Absorción Intestinal , Mucosa Intestinal/metabolismo , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Especificidad de la Especie , Esputo/metabolismo , PorcinosRESUMEN
AIM: The purpose of this study was to develop a novel thiolated starch polymer with improved mucoadhesive properties by conjugation of cysteamine to starch as a natural polymer of restricted mucoadhesive properties. METHODS: Aldehyde substructures were integrated into starch via oxidative cleavage of vicinal diols by increasing amounts of sodium periodate followed by covalent attachment of cysteamine to oxidized starch via reductive amination. Thiol groups were quantified via Ellman's reaction and their impact on mucoadhesion was analyzed by rheological investigations, the rotating cylinder method and tensile studies on porcine mucosa. RESULTS: The total amount of immobilized thiol groups revealed a correlation between degree of oxidation and thiolation. Modified starch demonstrated an up to 1.66-fold increase in water uptake in comparison to native starch. Modification of starch resulted in greatly improved cohesive properties and improvement in mucoadhesion. Rheological investigations revealed a 2- to 4-fold rise in viscosity of mucus. Tensile studies revealed a linear correlation between degree of oxidation/thiolation and enhancement of maximum detachment force and total work adhesion. CONCLUSION: In terms of these results, thiolated starch is a new, promising, polymer in the field of mucoadhesive drug delivery systems.
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Cisteamina/química , Mucosa Intestinal/química , Almidón/química , Adhesividad , Aldehídos/química , Animales , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Cisteamina/farmacología , Humanos , Reología , Almidón/farmacología , Porcinos , Resistencia a la TracciónRESUMEN
In complex abstract art, image composition (i.e., the artist's deliberate arrangement of pictorial elements) is an important aesthetic feature. We investigated whether the human brain detects image composition in abstract artworks automatically (i.e., independently of the experimental task). To this aim, we studied whether a group of 20 original artworks elicited a visual mismatch negativity when contrasted with a group of 20 images that were composed of the same pictorial elements as the originals, but in shuffled arrangements, which destroy artistic composition. We used a passive oddball paradigm with parallel electroencephalogram recordings to investigate the detection of image type-specific properties. We observed significant deviant-standard differences for the shuffled and original images, respectively. Furthermore, for both types of images, differences in amplitudes correlated with the behavioral ratings of the images. In conclusion, we show that the human brain can detect composition-related image properties in visual artworks in an automatic fashion.
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Arte , Electroencefalografía , Estética/psicología , Adulto , Potenciales Evocados/fisiología , Femenino , Humanos , Masculino , Estimulación Luminosa , Percepción Visual , Adulto JovenRESUMEN
BACKGROUND: The aim of the study was to develop an oral self-emulsifying drug delivery system (SEDDS) for exenatide and to evaluate its in vivo efficacy. METHODS: Exenatide was lipidised via hydrophobic ion pairing with sodium docusate (DOC) and incorporated in SEDDS consisting of 35% Cremophor EL, 25% Labrafil 1944, 30% Capmul-PG 8 and 10% propylene glycol. Exenatide/DOC was characterized in terms of lipophilicity evaluating the octanol/water phase distribution (logP). Exenatide/DOC SEDDS were characterized via droplet size analysis, drug release characteristics (log DSEDDS/release medium determination) and mucus permeation studies. Furthermore, the impact of orally administered exenatide/DOC SEDDS on blood glucose level was investigated in vivo on healthy male Sprague-Dawley rats. RESULTS: Hydrophobic ion pairing in a molar ratio of 1:4 (exenatide:DOC) increased the effective logP of exenatide from -1.1 to 2.1. SEDDS with a payload of 1% exenatide/DOC had a mean droplet size of 45.87⯱â¯2.9â¯nm and a Log DSEDDS/release medium of 1.9⯱â¯0.05. Permeation experiments revealed 2.7-fold improved mucus diffusion for exenatide/DOC SEDDS compared to exenatide in solution. Orally administered exenatide/DOC SEDDS showed a relative bioavailability (versus s.c.) of 14.62%⯱â¯3.07% and caused a significant (pâ¯<â¯.05) 20.6% decrease in AUC values of blood glucose levels. CONCLUSION: According to these results, hydrophobic ion pairing in combination with SEDDS represents a promising tool for oral peptide delivery.
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Sistemas de Liberación de Medicamentos/métodos , Emulsionantes/metabolismo , Exenatida/metabolismo , Administración Oral , Animales , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Emulsionantes/administración & dosificación , Exenatida/administración & dosificación , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/metabolismo , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The use of mucus permeating drug carrier systems being able to overcome the mucus barrier can lead to a remarkable enhancement in bioavailability. One promising approach is the design of mucolytic enzyme decorated carrier systems (MECS). These systems include micro- and nanoparticles as well as self-emulsifying drug delivery systems (SEDDS) decorated with mucin cleaving enzymes such as papain (PAP) or bromelain (BRO). MECS are able to cross the mucus barrier in a comparatively efficient manner by cleaving mucus substructures in front of them on their way to the epithelium. Thereby these enzymes hydrolyze peptide bonds of mucus glycoproteins forming tiny holes or passages through the mucus. In various in vitro and in vivo studies MECS proved to be superior in their mucus permeating properties over nanocarriers without enzyme decoration. PAP decorated nanoparticles, for instance, remained 3h after oral administration to an even 2.5-fold higher extend in rat small intestine than the corresponding undecorated nanoparticles permeating the intestinal mucus gel layer to a much lower degree. As MECS break up the mucus network only locally without destroying its overall protective barrier function, even long term treatments with such systems seem feasible. Within this review article we address different drug carrier systems decorated with various types of enzymes, their particular pros and cons and potential applications.
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Portadores de Fármacos/metabolismo , Enzimas/metabolismo , Moco/metabolismo , Animales , Portadores de Fármacos/química , Humanos , Nanopartículas/química , Nanopartículas/metabolismoRESUMEN
The aim of the study was to create a self-emulsifying drug delivery system (SEDDS) with mucolytic properties based on incorporated papain for improved mucus permeation. In order to increase the lipophilicity of the enzyme and to dissolve it in SEDDS, hydrophobic ion pairing with sodium deoxycholate in a molar ratio of 20:1 (surfactant: enzyme) was performed. The yield of precipitated papain was 86.8±2.7% and the ion pair was loaded into the formulations to 1% (m/m). Suitable formulations were chosen according to their properties to dissolve the ion pair and characterized regarding droplet size and polydispersity index. Prepared emulsions were in a droplet size range between 50 and 120nm. Enzyme activity assay of complex and loaded SEDDS was conducted to ensure proteolytic qualities for following permeation and diffusion studies. SEDDS loaded with the ion pair showed an almost 2-fold increase in mucus permeation compared to the control without complex. Furthermore, 3-fold enhanced mucus diffusion could be confirmed in a second assay and an increase of mucosal residence on porcine intestinal mucosa up to 3- and 5-fold was observed as against the blank formulations. Consequently the incorporation of enzymes exhibiting proteolytic properties in self-emulsifying drug delivery systems may be considered as a promising strategy to enhance mucus permeation and overcome intestinal barriers.