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This study investigates the fabrication and characterization of electrospun poly (ε-caprolactone)/poly (vinyl pyrrolidone) (PCL/PVP) fibers integrated with a nanocomposite of chitosan, silver nanocrystals, and graphene oxide (ChAgG), aimed at developing advanced wound dressing materials. The ChAgG nanocomposite, recognized for its antimicrobial and biocompatible properties, was incorporated into PCL/PVP fibers through electrospinning techniques. We assessed the resultant fibers' morphological, physicochemical, and mechanical properties, which exhibited significant enhancements in mechanical strength and demonstrated effective antimicrobial activity against common bacterial pathogens. The findings suggest that the PCL/PVP-ChAgG fibers maintain biocompatibility and facilitate controlled therapeutic delivery, positioning them as a promising solution for managing chronic and burn-related wounds. This study underscores the potential of these advanced materials to improve healing outcomes cost-effectively, particularly in settings plagued by high incidences of burn injuries. Further clinical investigations are recommended to explore these innovative fibers' full potential and real-world applicability.
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Vendajes , Quitosano , Grafito , Nanocompuestos , Poliésteres , Plata , Cicatrización de Heridas , Nanocompuestos/química , Cicatrización de Heridas/efectos de los fármacos , Grafito/química , Grafito/farmacología , Quitosano/química , Plata/química , Plata/farmacología , Poliésteres/química , Povidona/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Nanopartículas del Metal/química , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Quemaduras/tratamiento farmacológico , Quemaduras/terapia , Nanofibras/química , Pruebas de Sensibilidad MicrobianaRESUMEN
This study evaluates the antimicrobial efficacy of chitosan nanoparticles (CNPs), varying in size, against clinical isolates of Mycobacterium tuberculosis (MTB), E. coli, S. aureus, E. faecalis, and C. albicans, as well as the antimicrobial effects of aqueous extracts and lyophilized powders of Allium (garlic) species. CNPs were synthesized through ionotropic gelation and characterized by Z potential, hydrodynamic diameter (dynamic light scattering, DLS), and SEM. Aqueous garlic extracts were prepared via decoction. We assessed antimicrobial activity using disk diffusion and broth microdilution methods; in addition, a modified agar proportion method in blood agar was used for antimicrobial activity against MTB. CNPs inhibited MTB growth at 300 µg for 116.6 nm particles and 400 µg for 364.4 nm particles. The highest antimicrobial activity was observed against E. faecalis with nanoparticles between 200 and 280 nm. Allium sativum extract produced inhibition for C. albicans at 100 µg. The results indicate that CNPs possess significant antimicrobial properties against a range of pathogens, including MTB, at high concentrations. On the other hand, aqueous Allium sativum extracts exhibited antimicrobial activity. Nonetheless, due to their instability in solution, the use of lyophilized Allium sativum powder is preferable.
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Biomaterials, biodevices, and tissue engineering represent the cutting edge of medical science, promising revolutionary solutions to some of humanity's most pressing health challenges (Figure 1) [...].
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We synthesized seven (Z)-benzylidene-2-(E)-styryloxazol-5(4H)-ones derivatives of cinnamic acid and evaluated the ability of these compounds to inhibit human acetylcholinesterase (hAChE). The most potent compound was evaluated for cognitive improvement in short-term memory. The seven compounds reversibly inhibited the hAChE between 51 and 75% at 300 µM, showed an affinity (Ki) from 2 to 198 µM, and an IC50 from 9 to 246 µM. Molecular docking studies revealed that all binding moieties are involved in the non-covalent interactions with hAChE for all compounds. In addition, in silico pharmacokinetic analysis was carried out to predict the compounds' blood-brain barrier (BBB) permeability. The most potent inhibitor of hAChE significantly improved cognitive impairment in a modified Y-maze test (5 µmol/kg) and an Object Recognition Test (10 µmol/kg). Our results can help the rational design of hAChE inhibitors to work as potential candidates for treating cognitive disorders.
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Acetilcolinesterasa , Enfermedad de Alzheimer , Animales , Ratones , Humanos , Acetilcolinesterasa/metabolismo , Simulación del Acoplamiento Molecular , Oxazolona , Inhibidores de la Colinesterasa/química , Modelos Animales de Enfermedad , Cognición , Relación Estructura-ActividadRESUMEN
Nanofibers, which are formed by the electrospinning process, are used in a variety of applications. For this purpose, a specific diameter suited for each application is required, which is achieved by varying a set of parameters. This parameter adjustment process is empirical and works by trial and error, causing high input costs and wasting time and financial resources. In this work, an artificial neural network model is presented to predict the diameter of polyethylene nanofibers, based on the adjustment of 15 parameters. The model was trained from 105 records from data obtained from the literature and was then validated with nine nanofibers that were obtained and measured in the laboratory. The average error between the actual results was 2.29%. This result differs from those taken in an evaluation of the dataset. Therefore, the importance of increasing the dataset and the validation using independent data is highlighted.
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The primary mechanism for neuron death after an ischemic stroke is excitotoxic injury. Excessive depolarization leads to NMDA-mediated calcium entry to the neuron and, subsequently, cellular death. Therefore, the inhibition of the NMDA channel has been proposed as a neuroprotective measure in ischemic stroke. The high morbimortality associated with stroke warrants new therapies that can improve the functional prognosis of patients. Memantine is a non-competitive NMDA receptor antagonist which has gained attention as a potential drug for ischemic stroke. Here we analyze the available preclinical and clinical evidence concerning the use of memantine following an ischemic stroke. Preclinical evidence shows inhibition of the excitotoxic cascade, as well as improved outcomes in terms of motor and sensory function with the use of memantine. The available clinical trials of high-dose memantine in patients poststroke have found that it can improve patients' NIHSS and Barthel index and help patients with poststroke aphasia and intracranial hemorrhage. These results suggest that memantine has a clinically relevant neuroprotective effect; however, small sample sizes and other study shortcomings limit the impact of these findings. Even so, current studies show promising results that should serve as a basis to promote future research to conclusively determine if memantine does improve the outcomes of patients' post-ischemic stroke. We anticipate that future trials will fill current gaps in knowledge, and these latter results will broaden the therapeutic arsenal for clinicians looking to improve the prognosis of patients poststroke.
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Nanomedicine is a new discipline resulting from the combination of nanotechnology and biomedicine. Nanomedicine has contributed to the development of new and improved treatments, diagnoses, and therapies. In this field, nanoparticles have notable importance due to their unique properties and characteristics, which are useful in different applications, including tissue engineering, biomarkers, and drug delivery systems. Electrospinning is a versatile technique used to produce fibrous mats. The high surface area of the electrospun mats makes them suitable for applications in fields using nanoparticles. Electrospun mats are used for tissue engineering, wound dressing, water-treatment filters, biosensors, nanocomposites, medical implants, protective clothing materials, cosmetics, and drug delivery systems. The combination of nanoparticles with nanofibers creates hybrid systems that acquire properties that differ from their components' characteristics. By utilizing nanoparticles and nanofibers composed of dissimilar polymers, the two synergize to improve the overall performance of electrospinning mats and nanoparticles. This review summarizes the hybrid systems of polymeric nanoparticles and polymeric nanofibers, critically analyzing how the combination improves the properties of the materials and contributes to the reduction of some disadvantages found in nanometric devices and systems.
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OBJECTIVE: the aim of the present article was to test a self-care model explained by the relationship between self-efficacy, body image, obsessive-compulsive disorder, and depression in people with bariatric surgery in the city of Tijuana, Baja California, Mexico. METHOD: this was a correlational cross-sectional study carried out between August and December 2020. Validated instruments were administered to 102 participants to measure their self-care capacity, general self-efficacy, psychopathological symptoms, and body image perception and satisfaction. The variables of interest were analyzed using descriptive statistics and the Pearson and Spearman correlation coefficients were used to develop a model using path analysis. RESULT: a significant model was obtained with adequate goodness-of-fit indicators (chi-square χ2 (8) = 11.451, p = .177; root mean square error of approximation (RMSEA)= 0.000; goodness-of-fit index (GFI)= 0.965; comparative fit index (CFI)= 0.985; parsimonious normed fit index (PNFI)= 0.509, and Akaike information criterion (AIC)= 37.451). Self-efficacy (Zß=0.294) and body image dissatisfaction (So= -0.376) were shown to influence self-care abilities while psychopathological symptoms influenced body dissatisfaction: obsessive-compulsive disorder (Zß=0.370) and depression (Zß=0.320). CONCLUSION: adequate levels of self-efficacy and body satisfaction predict a high capacity for self-care.
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Cirugía Bariátrica , Imagen Corporal , Adulto , Estudios Transversales , Humanos , México , Reproducibilidad de los Resultados , Autocuidado , Encuestas y CuestionariosRESUMEN
The spontaneous interaction between human papillomavirus type 16 (HPV16) L1 virus-like particles (VLPs) and non-functionalized gold nanoparticles (nfGNPs) interferes with the nfGNPs' salt-induced aggregation, inhibiting the red-blue color shift in the presence of NaCl. Electron microscopy and competition studies showed that color-shift inhibition is a consequence of direct nfGNP-VLP interaction and, thus, may produce a negative impact on the virus entry cell process. Here, an in vitro infection system based on the HPV16 pseudovirus (PsV) was used to stimulate the natural infection process in vitro. PsVs carry a pseudogenome with a reporter gene, resulting in a fluorescent signal when PsVs infect a cell, allowing quantification of the viral infection process. Aggregation assays showed that nfGNP-treated PsVs also inhibit color shift in the presence of NaCl. High-resolution microscopy confirmed nfGNP-PsV complex formation. In addition, PsVs can interact with silver nanoparticles, suggesting a generalized interaction of metallic nanoparticles with HPV16 capsids. The treatment of PsVs with nfGNPs produced viral infection inhibition at a higher level than heparin, the canonical inhibitor of HPV infection. Thus, nfGNPs can efficiently interfere with the HPV16 cell entry process and may represent a potential active component in prophylactic formulations to reduce the risk of HPV infection.
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Nanopartículas del Metal , Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Proteínas de la Cápside/genética , Oro/farmacología , Oro/uso terapéutico , Papillomavirus Humano 16/genética , Humanos , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/virología , Infecciones por Papillomavirus/prevención & control , Plata , Cloruro de Sodio/farmacologíaRESUMEN
Augmenting bacterial growth is of great interest to the biotechnological industry. Hence, the effect of poly (caprolactone) fibrous scaffolds to promote the growth of different bacterial strains of biological and industrial interest was evaluated. Furthermore, different types of carbon (glucose, fructose, lactose and galactose) and nitrogen sources (yeast extract, glycine, peptone and urea) were added to the scaffold to determinate their influence in bacterial growth. Bacterial growth was observed by scanning electron microscopy; thermal characteristics were also evaluated; bacterial cell growth was measured by ultraviolet-visible spectrophotometry at 600-nm. Fibers produced have an average diameter between 313 to 766 nm, with 44% superficial porosity of the scaffolds, a glass transition around ~64 °C and a critical temperature of ~338 °C. The fibrous scaffold increased the cell growth of Escherichia coli by 23% at 72 h, while Pseudomonas aeruginosa and Staphylococcus aureus increased by 36% and 95% respectively at 48 h, when compared to the normal growth of their respective bacterial cultures. However, no significant difference in bacterial growth between the scaffolds and the casted films could be observed. Cell growth depended on a combination of several factors: type of bacteria, carbon or nitrogen sources, casted films or 3D scaffolds. Microscopy showed traces of a biofilm formation around 3 h in culture of P. aeruginosa. Water bioremediation studies showed that P. aeruginosa on poly (caprolactone)/Glucose fibers was effective in removing 87% of chromium in 8 h.
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Resumo Objetivo: testar um modelo de autocuidado explicado pela relação entre autoeficácia, imagem corporal, transtorno obsessivo-compulsivo e depressão em pessoas com cirurgia bariátrica na cidade de Tijuana, no México. Método: estudo transversal correlacional realizado entre agosto e dezembro de 2020. Instrumentos validados foram aplicados a 102 participantes para medir sua capacidade de autocuidado, autoeficácia geral, sintomas psicopatológicos, e percepção e satisfação com a imagem corporal. As variáveis de interesse foram analisadas utilizando estatísticas descritivas e correlações de Pearson e Spearman para finalmente desenvolver um modelo utilizando a análise de caminho (path analysis). Resultados: foi obtido um modelo significativo com bons indicadores de bondade de ajuste (qui-quadrado χ 2 (8)= 11,451, p = 0,177; raiz quadrada da média do erro de aproximação (RMSEA)= 0,000; índice de bondade de ajuste (GFI)= 0,965; índice de ajuste comparativo (CFI)= 0,985; índice de ajuste normalizado parcimonioso (PNFI)= 0,509 e critério de informação de Akaike (AIC)= 37,451). A autoeficácia (Zβ= 0,294) e a insatisfação com a imagem corporal (Zβ= -0,376) demonstraram ter um efeito sobre as capacidades de autocuidado, enquanto os sintomas psicopatológicos influenciam a insatisfação corporal: transtorno obsessivo-compulsivo (Zβ= 0,370) e depressão (Zβ= 0,320). Conclusão: níveis adequados de autoeficácia e satisfação corporal predizem uma alta capacidade de autocuidado.
Abstract Objective: the aim of the present article was to test a self-care model explained by the relationship between self-efficacy, body image, obsessive-compulsive disorder, and depression in people with bariatric surgery in the city of Tijuana, Baja California, Mexico. Method: this was a correlational cross-sectional study carried out between August and December 2020. Validated instruments were administered to 102 participants to measure their self-care capacity, general self-efficacy, psychopathological symptoms, and body image perception and satisfaction. The variables of interest were analyzed using descriptive statistics and the Pearson and Spearman correlation coefficients were used to develop a model using path analysis. Result: a significant model was obtained with adequate goodness-of-fit indicators (chi-square χ2 (8) = 11.451, p = .177; root mean square error of approximation (RMSEA)= 0.000; goodness-of-fit index (GFI)= 0.965; comparative fit index (CFI)= 0.985; parsimonious normed fit index (PNFI)= 0.509, and Akaike information criterion (AIC)= 37.451). Self-efficacy (Zβ=0.294) and body image dissatisfaction (So= -0.376) were shown to influence self-care abilities while psychopathological symptoms influenced body dissatisfaction: obsessive-compulsive disorder (Zβ=0.370) and depression (Zβ=0.320). Conclusion: adequate levels of self-efficacy and body satisfaction predict a high capacity for self-care.
Resumen Objetivo: probar un modelo de autocuidado explicado por la relación entre autoeficacia, imagen corporal, obsesión-compulsión y depresión en personas con cirugía bariátrica de la ciudad de Tijuana, B.C. Método: estudio transversal correlacional realizado entre agosto y diciembre de 2020. Se aplicaron instrumentos validados a 102 participantes para medir su capacidad de autocuidado, autoeficacia general, síntomas psicopatológicos, percepción y satisfacción de la imagen corporal. Las variables de interés fueron analizadas mediante estadística descriptiva y correlaciones de Pearson y Spearman para finalmente elaborar un modelo mediante análisis de ruta (Path Analysis). Resultados: se obtuvo un modelo significativo con buenos indicadores de bondad de ajuste (chi-cuadrado χ 2 (8)= 11.451, p = .177; error de aproximación raíz-media-cuadrada (RMSEA)= 0.000; índice de bondad de ajuste (GFI)= 0.965; índice de ajuste comparativo (CFI)= 0.985; índice de ajuste normado parsimonioso (PNFI)= 0.509 y criterio de información de Akaike (AIC)= 37.451). Se demostró que la autoeficacia (Zβ= 0.294) y la insatisfacción de la imagen corporal (Zβ= -0.376) tienen un efecto sobre las capacidades de autocuidado mientras que los síntomas psicopatológicos influyen sobre la insatisfacción corporal: obsesión-compulsión (Zβ= 0.370) y depresión (Zβ= 0.320). Conclusión: los niveles adecuados de autoeficacia y satisfacción corporal predicen una alta capacidad de autocuidado.
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Humanos , Masculino , Femenino , Adulto , Autocuidado , Imagen Corporal/psicología , Autoeficacia , Cirugía Bariátrica/psicología , MéxicoRESUMEN
BACKGROUND AND OBJECTIVES: Micronutrient deficiencies are common among bariatric patients; this study aimed to determine whether a cognitive dissonance-based virtual program improved adherence to multivitamin use in bariatric patients from northern Mexico. METHODS AND STUDY DESIGN: A randomized controlled trial of the supplementation strategy was conducted over three months. The participants were randomized to an intervention or waitlisted control group and received two psycho-educative and four cognitive dissonance virtual sessions. Multiple linear regression was used to determine standardized estimates of associations between the intervention and dependent variables. Two path analyses were evaluated considering baseline and post-test measurements. RESULTS: Intervention was associated with higher concentrations of Hb (ß=0.758, p<0.001), vitamin D (ß=0.577, p<0.001), iron (ß=0.523, p<0.001), folate (ß=0.494, p<0.01), calcium (ß=0.452, p<0.01), higher adherence (ß=0.467, p<0.001), and level of knowledge (ß=0.298, p<0.05. CONCLUSIONS: The dissonance-based intervention potentiated the level of supplementation adherence. A higher level of adherence was reflected in micronutrient concentrations, thus providing confirmation of intervention. Thus, support is found for a multidisciplinary clinical practice that enhances nutrition status after bariatric surgery for obesity.
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Cirugía Bariátrica , Obesidad Mórbida , Disonancia Cognitiva , Suplementos Dietéticos , Ácido Fólico , Humanos , Micronutrientes , VitaminasRESUMEN
OBJECTIVES: To summarize the procedure for reporting adverse drug reactions (ADRs) in a Mexican hospital, with the purpose of promoting and facilitating the report of ADRs by the heath team. We outline the relevance of pharmacists in performing these activities in Mexican hospitals. METHODS: A pharmacovigilance study was carried out following the establishment of the Pharmacovigilance Unit of a Mexican hospital on January 2014 through March 2019. KEY FINDINGS: There is an undernotification rate of ADRs, since only 137 ADRs were notified in a five-year period, mostly by biopharmaceutical chemists holding bachelor's degrees that were acting as pharmacists. CONCLUSIONS: To improve the safety of medications, it is necessary to improve ADR notifications in Mexico's health system. One important step in this direction is to establish a Pharmacy degree with training for promoting and performing ADR notifications.
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Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Farmacéuticos/organización & administración , Farmacovigilancia , Hospitales , Humanos , México , Servicio de Farmacia en Hospital/organización & administración , Rol ProfesionalRESUMEN
Electrospun nanofibers have been widely studied for many medical applications. They can be designed with specific features, including mucoadhesive properties. This review summarizes the polymeric scaffolds obtained by the electrospinning process that has been applied for drug release in different mucosal sites such as oral, ocular, gastroenteric, vaginal, and nasal. We analyzed the electrospinning parameters that have to be optimized to create reproducible and efficient mucoadhesive nanofibers, among them are: electrical field, polymer concentration, viscosity, flow rate, needle-collector distance, solution conductivity, solvent, environmental parameters, and electrospinning setup. We also revised the mucoadhesive theories as well as the mucoadhesive properties of the polymers used. This review shows that the most studied mucosal site is the oral cavity, because it is accessible and easy to evaluate, while the rest are uncomfortable for the patient and difficult to assess in vivo. We found problems that need to be solved for mucoadhesive electrospun nanofibers, such as improving adhesion strength and mucosal permanence time, and the design of unidirectional release, multilayer systems for the treatment of several pathologies, to ensure the drug concentration in the tissue or target organ.
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Sistemas de Liberación de Medicamentos/métodos , Moco/química , Nanofibras/química , Polímeros/química , Adhesividad , Conductividad Eléctrica , HumanosRESUMEN
The electrospinning technique is a useful and versatile approach for conversion of polymeric solutions into continuous fibers, ranging from a few micrometers (10-100 µm) to the scale of nanometers (10- 100 nm) in diameters. This technique can be used in a vast number of polymers, in some cases after modifying them to the required properties. The high surface-to-volume ratio of the fibers can improve some processes like cell binding and proliferation, drug loading, and mass transfer processes. One of the most important and studied areas of electrospinning is in the drug delivery field, for the controlled release of active substances ranging from antibiotics and anticancer agents, to macromolecules such as proteins and DNA. The advantage of this method is that a wide variety of low solubility drugs can be loaded into the fibers to improve their bioavailability or to attain controlled release. This review presents an overview of the reported drugs loaded into electrospun polymeric nanofibers to be used as drug delivery systems. These drugs are classified by their applications in pharmacy.
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Antibacterianos/química , Antineoplásicos/química , Sistemas de Liberación de Medicamentos , Nanofibras/química , Polímeros/química , Portadores de Fármacos/química , Electricidad , Humanos , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
This study aims to determine the degree of acetylcholinesterase inhibition and neurological symptoms for each of the psychiatric disorders diagnosed in the farm workers of a rural population in the state of Baja California, Mexico. We conducted a cross-sectional study on 140 agricultural workers (exposed participants). The study was run using the Mini International Neuropsychiatric Interview Diagnostic Test (MINI), a pre-established questionnaire to diagnose the mental state of each agricultural worker. Analysis of enzymatic activity was carried out using the modified Ellman method. The results showed that, among agricultural workers with slightly inhibited enzymatic activity, 25% met the criteria for the diagnosis of major depression with suicidal attitudes, 23.9% with inhibited enzymatic activity showed generalized anxiety, 23.5% showed combined depressionâ»anxiety, and 22% met the criteria for major depression and no psychiatric diagnosis disorder. These results suggest the need for the development of effective public-health strategies to inform farm workers about integrated pesticide management in order to prevent serious health complications.
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Enfermedades de los Trabajadores Agrícolas/epidemiología , Enfermedades de los Trabajadores Agrícolas/etiología , Trastornos Mentales/epidemiología , Trastornos Mentales/etiología , Exposición Profesional/estadística & datos numéricos , Intoxicación por Organofosfatos/complicaciones , Intoxicación por Organofosfatos/epidemiología , Acetilcolinesterasa/sangre , Adolescente , Adulto , Enfermedades de los Trabajadores Agrícolas/diagnóstico , Estudios Transversales , Agricultores , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , México/epidemiología , Persona de Mediana Edad , Exposición Profesional/análisis , Intoxicación por Organofosfatos/diagnóstico , Psicometría/estadística & datos numéricos , Población Rural , Adulto JovenRESUMEN
Recently, electrospun polymeric nanofibers have proven to be an interesting strategy for drug delivery systems application. The high surface-to-volume ratio of the fibers can improve some processes, such as cell binding and proliferation, drug loading, and mass transfer processes. One of the most important and studied areas of electrospinning is in the drug delivery field, for the controlled release of active substances ranging from antibiotics and anticancer agents to macromolecules such as proteins and DNA. The advantage of this method is that a wide variety of low solubility drugs can be loaded into the fibers to improve their bioavailability or to attain controlled release. This review presents an overview of the reported drugs loaded into polymeric nanofibers, to be used as drug delivery systems. For instance, it presents the reports on drugs with different bioactivities such as antiinflammatory, anti-microbial, anticancer, cardiovascular, anti-histamine, gastrointestinal, palliative and contraceptive drugs, etc. It also analyzes the electrospinning techniques used in each system, as well as the polymers used as matrices for the preparation of the nanofibers; unfolding the advantages of electrospun polymeric nanofibers over other drug delivery systems. This review intends to enlist and summarize the reported literature concerning this topic. In addition, it proposes future research in the field.
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Antibacterianos/química , Antineoplásicos/química , Biopolímeros/química , Sistemas de Liberación de Medicamentos , Nanofibras/química , Animales , HumanosRESUMEN
Through studies with ligand binding to the acetylcholine binding protein (AChBP), we previously identified a series of 4,6-substituted 2-aminopyrimidines that associate with this soluble surrogate of the nicotinic acetylcholine receptor (nAChR) in a cooperative fashion, not seen for classical nicotinic agonists and antagonists. To examine receptor interactions of this structural family on ligand-gated ion channels, we employed HEK cells transfected with cDNAs encoding three requisite receptor subtypes: α7-nAChR, α4ß2-nAChR, and a serotonin receptor (5-HT3AR), along with a fluorescent reporter. Initial screening of a series of over 50 newly characterized 2-aminopyrimidines with affinity for AChBP showed only two to be agonists on the α7-nAChR below 10 µM concentration. Their unique structural features were incorporated into design of a second subset of 2-aminopyrimidines yielding several congeners that elicited α7 activation with EC50 values of 70 nM and Kd values for AChBP in a similar range. Several compounds within this series exhibit specificity for the α7-nAChR, showing no activation or antagonism of α4ß2-nAChR or 5-HT3AR at concentrations up to 10 µM, while others were weaker antagonists (or partial agonists) on these receptors. Analysis following cocrystallization of four ligand complexes with AChBP show binding at the subunit interface, but with an orientation or binding pose that differs from classical nicotinic agonists and antagonists and from the previously analyzed set of 2-aminopyrimidines that displayed distinct cooperative interactions with AChBP. Orientations of aromatic side chains of these complexes are distinctive, suggesting new modes of binding at the agonist-antagonist site and perhaps an allosteric action for heteromeric nAChRs.
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Acetilcolina/metabolismo , Proteínas Portadoras/metabolismo , Pirimidinas/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Acetilcolina/química , Proteínas Portadoras/química , Cristalografía por Rayos X , Células HEK293 , Humanos , Modelos Moleculares , Estructura Molecular , Pirimidinas/química , Receptor Nicotínico de Acetilcolina alfa 7/química , Receptor Nicotínico de Acetilcolina alfa 7/aislamiento & purificaciónRESUMEN
Nowadays, electrospinning has become one of the most versatile, easy, and cost-effective techniques to engineer advanced materials used for many applications, especially in the biomedical and environmental areas. Like the numerous patents around the world, the increasing number of papers witnesses the huge potential of this simple process, and many companies have been emerged during the last years to exploit its innumerable applications. This article presents a critically selected overview of polymers that can be used to produce nanofibers, along with the biomedical applications of the resulting electrospun scaffolds. We have focused on about seven natural and synthetic polymers, but many more can be found in the literature, either as their pristine state or as composites with ceramics, metals, and other polymers. The description of some strategies for nanofiber production, and the characterization used to evaluate their optimization, has been discussed. Finally, several polymers have been recognized as highlights for future work.