RESUMEN
Oral Topiramate therapy is associated with systemic adverse effects including paresthesia,abdominal pain, and fluctuations in plasma levels. The purpose of this research was to develop an intranasal in situ gel based system comprising Topiramate polymeric nanoparticles and evaluate its potential both in vitro and in vivo. Poly (lactic-co-glycolic acid) (PLGA)nanoparticles prepared by nanoprecipitation method were added into the in situ gelling system of Poloxamer 407 and HPMC K4M. Selected formulation (TG5) was evaluated for physicochemical properties, nasal permeation and in vivo pharmacokinetics in rats. PLGAnanoparticles (O1) exhibited low particle size (~ 144.4 nm), good polydispersity index (0.202), negative zeta potential (-12.7 mV), and adequate entrapment efficiency (64.7%). Developed in situ gel showed ideal pH (6.5), good gelling time (35 s), gelling temperature(37â), suitable viscosity (1335 cP)and drug content of 96.2%. In vitro drug release conformedto Higuchi release kinetics, exhibiting a biphasic pattern of initial burst release and sustained release for 24 h. Oral administration of the drug to Sprague-Dawley rats (G3) showed higher plasma Cmax(504 ng/ml, p < 0.0001) when compared to nasal delivery of in situ gel (G4) or solution (G5). Additionally, AUC0-α of G3 (8786.82 ng/ml*h) was considerably higher than othergroups. Brain uptake data indicates a higher drug level with G4 (112.47 ng /ml) at 12 h when compared to G3. Histopathological examination of groups; G1 (intranasal saline), G2(intranasal placebo), G3, G4, and G5 did not show any lesions of pathological significance. Overall, the experimental results observed were promising and substantiated the potential of developed in situ gel for intranasal delivery.
Asunto(s)
Administración Intranasal , Encéfalo , Geles , Nanopartículas , Mucosa Nasal , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ratas Sprague-Dawley , Topiramato , Animales , Topiramato/administración & dosificación , Topiramato/farmacocinética , Nanopartículas/química , Ratas , Administración Intranasal/métodos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Mucosa Nasal/metabolismo , Mucosa Nasal/efectos de los fármacos , Masculino , Tamaño de la Partícula , Fructosa/administración & dosificación , Fructosa/farmacocinética , Fructosa/química , Portadores de Fármacos/química , Liberación de Fármacos , Sistemas de Liberación de Medicamentos/métodos , Ácido Láctico/química , Ácido Láctico/administración & dosificación , Ácido Poliglicólico/química , Administración OralRESUMEN
Neurodegenerative disorder refers to malfunctioning of neurons their degradation leading to death of neurons. Among various neurodegenerative disorders APHD (Alzheimer's, Parkinson's, and Huntington's Disease) are particularly concerning due to their progressive and debilitating nature. The therapeutic agent used for treatment and management of APHD often show unsatisfactory clinical outcome owing to poor solubility and limited permeability across blood brain barrier (BBB). The nose-to brain delivery can overcome this BBB challenge as it can transport drug directly to brain though olfactory pathways bypassing BBB. Additionally, the nanotechnology has emerged as a cutting-edge methodology to address this issue and specifically mucoadhesive micro/nanoemulsion can improve the overall performance of the drug when administered intranasally. Beyond the therapy neurotechnology has emerged as are revolutionary AI-driven BCI (Brain computer interface) aimed to restore independence in patients with function loss due to neuron degeneration/death. A promising BCI Neuralink has been recently explored for clinical trials and results revealed that a quadriplegia bearing person with implanted Neuralink chip was able to perform few normal functions of daily routine such as playing online games, text messaging, reading, and learning foreign languages online through accessing the particular websites. This review will discuss the fundamental concepts of neurodegeneration, application of micro/nanoemulsion through intranasal route and integration of neurotechnology for the management and treatment of APHD.
Asunto(s)
Administración Intranasal , Sistemas de Liberación de Medicamentos , Emulsiones , Nanotecnología , Enfermedades Neurodegenerativas , Administración Intranasal/métodos , Humanos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Nanotecnología/métodos , Animales , Barrera Hematoencefálica/metabolismo , Nanopartículas/química , Nanopartículas/administración & dosificaciónRESUMEN
Background: The management of preoperative anxiety in pediatric patients, as well as its implications, has remained challenging for anesthesiologists. In this study, we compared the safety and efficacy of intranasal dexmedetomidine, midazolam, and ketamine as surgical premedication in children. Methods: This double-blinded randomized clinical trial was conducted at two tertiary hospitals in January 2014, on 90 children aged between 2-7 years old. The participants' American Society of Anesthesiologists (ASA) physical status was I or II, and they were scheduled for elective unilateral inguinal herniorrhaphy. Using the block randomization method, the patients were randomly assigned to three groups, each receiving intranasal dexmedetomidine (2 µg/Kg), midazolam (0.2 mg/Kg), and ketamine (8 mg/Kg) 60 min before induction of anesthesia. Anxiety and sedation state were evaluated before drug administration, and then every 10 min for the next 50 min. Parental separation anxiety, mask acceptance, postoperative agitation, pain, nausea, and vomiting were also recorded and compared between these groups. All the statistical analyses were performed using SPSS software (version 21.0). P<0.05 was considered statistically significant. Results: Ketamine indicated the strongest sedative effect 10, 20, and 30 min after administration of premedication (P<0.001, P=0.03, P=0.01, respectively). However, dexmedetomidine was more effective than other drugs after 40 and 50 min (P<0.001). Other variables indicated no statistically significant difference. Conclusion: In case of emergencies, intranasal ketamine, with the shortest time of action, could be administered. Intranasal dexmedetomidine, which was revealed to be the most potent drug in this study, could be administrated 40-50 min before elective pediatric surgeries.Trial registration number: IRCT2013081614372N1.
Asunto(s)
Administración Intranasal , Dexmedetomidina , Hipnóticos y Sedantes , Ketamina , Midazolam , Humanos , Ketamina/uso terapéutico , Ketamina/farmacología , Ketamina/administración & dosificación , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Dexmedetomidina/administración & dosificación , Midazolam/uso terapéutico , Midazolam/farmacología , Midazolam/administración & dosificación , Preescolar , Masculino , Femenino , Niño , Administración Intranasal/métodos , Hipnóticos y Sedantes/farmacología , Hipnóticos y Sedantes/uso terapéutico , Hipnóticos y Sedantes/administración & dosificación , Método Doble Ciego , Procedimientos Quirúrgicos Ambulatorios/métodos , Ansiedad/tratamiento farmacológicoRESUMEN
The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 32-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study's factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment.
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Administración Intranasal , Epilepsia , Geles , Mucosa Nasal , Triterpenos , Animales , Administración Intranasal/métodos , Epilepsia/tratamiento farmacológico , Geles/química , Mucosa Nasal/metabolismo , Mucosa Nasal/efectos de los fármacos , Masculino , Triterpenos/administración & dosificación , Triterpenos/farmacocinética , Triterpenos/farmacología , Triterpenos/química , Temperatura , Saponinas/administración & dosificación , Saponinas/química , Saponinas/farmacología , Saponinas/farmacocinética , Química Farmacéutica/métodos , Disponibilidad Biológica , Ratas , Poloxámero/química , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/farmacología , Anticonvulsivantes/químicaRESUMEN
Verapamil hydrochloride (VRP), an antihypertensive calcium channel blocker drug has limited bioavailability and short half-life when taken orally. The present study was aimed at developing cubosomes containing VRP for enhancing its bioavailability and targeting to brain for cluster headache (CH) treatment as an off-label use. Factorial design was conducted to analyze the impact of different components on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and percent drug release. Various in-vitro characterizations were performed followed by pharmacokinetic and brain targeting studies. The results revealed the significant impact of glyceryl monooleate (GMO) on increasing EE%, PS, and ZP of cubosomes with a negative influence on VRP release. The remarkable effect of Poloxamer 407 (P407) on decreasing EE%, PS, and ZP of cubosomes was observed besides its influence on accelerating VRP release%. The DSC thermograms indicated the successful entrapment of the amorphous state of VRP inside the cubosomes. The design suggested an optimized formulation containing GMO (50% w/w) and P407 (5.5% w/w). Such formulation showed a significant increase in drug permeation through nasal mucosa with high Er value (2.26) when compared to VRP solution. Also, the histopathological study revealed the safety of the utilized components used in the cubosomes preparation. There was a significant enhancement in the VRP bioavailability when loaded in cubosomes owing to its sustained release favored by its direct transport to brain. The I.N optimized formulation had greater BTE% and DTP% at 183.53% and 90.19%, respectively in comparison of 41.80% and 59% for the I.N VRP solution.
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Administración Intranasal , Encéfalo , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Glicéridos , Mucosa Nasal , Tamaño de la Partícula , Verapamilo , Administración Intranasal/métodos , Animales , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Verapamilo/administración & dosificación , Verapamilo/farmacocinética , Distribución Tisular , Glicéridos/química , Mucosa Nasal/metabolismo , Disponibilidad Biológica , Ratas , Bloqueadores de los Canales de Calcio/farmacocinética , Bloqueadores de los Canales de Calcio/administración & dosificación , Poloxámero/química , Masculino , Química Farmacéutica/métodos , Ratas Wistar , Nanopartículas/químicaRESUMEN
Central nervous system-related disorders have become a continuing threat to human life and the current statistic indicates an increasing trend of such disorders worldwide. The primary therapeutic challenge, despite the availability of therapies for these disorders, is to sustain the drug's effective concentration in the brain while limiting its accumulation in non-targeted areas. This is attributed to the presence of the blood-brain barrier and first-pass metabolism which limits the transportation of drugs to the brain irrespective of popular and conventional routes of drug administration. Therefore, there is a demand to practice alternative routes for predictable drug delivery using advanced drug delivery carriers to overcome the said obstacles. Recent research attracted attention to intranasal-to-brain drug delivery for promising targeting therapeutics in the brain. This review emphasizes the mechanisms to deliver therapeutics via different pathways for nose-to-brain drug delivery with recent advancements in delivery and formulation aspects. Concurrently, for the benefit of future studies, the difficulties in administering medications by intranasal pathway have also been highlighted.
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Administración Intranasal , Encéfalo , Sistemas de Liberación de Medicamentos , Animales , Humanos , Administración Intranasal/métodos , Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Mucosa Nasal/metabolismo , Preparaciones Farmacéuticas/administración & dosificaciónRESUMEN
Eugenol (Eug) holds potential as a treatment for bacterial rhinosinusitis by nasal powder drug delivery. To stabilization and solidification of volatile Eug, herein, nasal inhalable γ-cyclodextrin metal-organic framework (γ-CD-MOF) was investigated as a carrier by gas-solid adsorption method. The results showed that the particle size of Eug loaded by γ-CD-MOF (Eug@γ-CD-MOF) distributed in the range of 10-150 µm well. In comparison to γ-CD and ß-CD-MOF, γ-CD-MOF has higher thermal stability to Eug. And the intermolecular interactions between Eug and the carriers were verified by characterizations and molecular docking. Based on the bionic human nasal cavity model, Eug@γ-CD-MOF had a high deposition distribution (90.07 ± 1.58%). Compared with free Eug, the retention time Eug@γ-CD-MOF in the nasal cavity was prolonged from 5 min to 60 min. In addition, the cell viability showed that Eug@γ-CD-MOF (Eug content range 3.125-200 µg/mL) was non-cytotoxic. And the encapsulation of γ-CD-MOF could not reduce the bacteriostatic effect of Eug. Therefore, the biocompatible γ-CD-MOF could be a potential and valuable carrier for nasal drug delivery to realize solidification and nasal therapeutic effects of volatile oils.
Asunto(s)
Administración Intranasal , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Eugenol , Estructuras Metalorgánicas , Polvos , Estructuras Metalorgánicas/química , Polvos/química , Humanos , Eugenol/química , Eugenol/administración & dosificación , Eugenol/farmacología , Administración Intranasal/métodos , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos , Simulación del Acoplamiento Molecular/métodos , gamma-Ciclodextrinas/química , Estabilidad de Medicamentos , Antibacterianos/administración & dosificación , Antibacterianos/química , Antibacterianos/farmacología , Ciclodextrinas/química , Cavidad Nasal/metabolismoRESUMEN
The nasal administration of therapeutic fluids and vaccines is used to treat allergic rhinitis, sinusitis, congestion, coronaviruses and even Alzheimer's disease. In the latter, the drug must reach the olfactory region, so it finds its way into the central nervous system. Effective administration techniques able to reach the olfactory region are challenging due to the tortuous anatomy of the nasal cavity, and are frequently evaluated in vitro using transparent anatomical models. Here, the liquid distribution inside a 3D printed human nasal cavity is quantified for model fluids resulting from the discharge of a 1-mL syringe with either a spray-generating nozzle, and a straight tip emitting a collimated fluid stream. Experiments using two model fluids with different viscosities suggest that a simple, correctly positioned straight tip attached to a syringe is able to efficiently deliver most of a therapeutic fluid in the human olfactory region in the side-laying position, avoiding the adoption of head-back and head-down positions that can be difficult for patients in the age range typical of Alzheimer's disease. Furthermore, we demonstrate by computer simulations that the conclusion is valid within a wide range of parameters.
Asunto(s)
Administración Intranasal , Simulación por Computador , Cavidad Nasal , Humanos , Administración Intranasal/métodos , Modelos Anatómicos , Impresión Tridimensional , Viscosidad , Sistemas de Liberación de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/instrumentaciónRESUMEN
The aim of the present study was to develop and evaluate intranasal formulations of the thermoreversible fluoxetine cubosomal in situ gel. This gel was intended for permeation and bioavailability enhancement to target the brain effectively by bypassing the blood-brain barrier (BBB). Fluoxetine-loaded cubosomes were prepared by the homogenization method followed by the cold method approach to develop in situ gel. Fluoxetine-loaded cubosomes displayed a higher encapsulation efficiency (82.60 ± 1.25%) than fluoxetine. This might be due to the solubilizing activity of the polymer to cause partitioning of the lipophilic drug into the aqueous phase during the change from the cubic gel phase to cubosomes. In vitro analysis of fluoxetine-loaded cubosomal in situ gel showed a sustained release profile (93.22 ± 2.47%) due to limited diffusion of fluoxetine. The formation of strong affinity bonds of the drug with GMO (drug transporter) decreased the drug release in comparison to that with fluoxetine-loaded cubosomes (90.68 ± 1.74%). The ex vivo drug release profile revealed the drug release of 96.31 ± 2.88% by the end of 24 h. This is attributed to the higher capability of the intranasal cubosomal in situ gel to prolong the retention and enable better permeation through the nasal mucosa. In male Wistar rats, in vivo biodistribution studies for cubosomal in situ gel administered via the intranasal route at a dose of 3.5 mg/kg demonstrated an increase in pharmacokinetic parameters like the AUC (406 ± 75.35 µg/mL), Cmax (368.07 ± 0.23 µg/mL), Tmax (4 h), and t1/2 (14.06 h). The mucoadhesive nature of the in situ gel led to an increase in the residence time of the gel in the nasal mucosa. The biodistribution study of intranasal in situ cubosomal gel improved the bioavailability 2.21-fold in comparison to that with the cubosomal dispersion but 2.83-fold in comparison to that with the drug solution. Therefore, fluoxetine-loaded cubosomal in situ gel proved as a promising carrier for effective transportation of fluoxetine via the intranasal route with significant brain bioavailability.
Asunto(s)
Administración Intranasal , Disponibilidad Biológica , Encéfalo , Fluoxetina , Fluoxetina/farmacocinética , Fluoxetina/administración & dosificación , Fluoxetina/química , Administración Intranasal/métodos , Animales , Encéfalo/metabolismo , Barrera Hematoencefálica/metabolismo , Liberación de Fármacos , Ratas , Mucosa Nasal/metabolismo , Masculino , Geles/química , Ratas Wistar , Composición de Medicamentos/métodosRESUMEN
Adequate drug delivery across the blood-brain barrier (BBB) is a critical factor in treating central nervous system (CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization, the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2 (LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine (PLL) and negatively charged surface of fibers; this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.
Asunto(s)
Administración Intranasal , Mucosa Nasal , Animales , Administración Intranasal/métodos , Mucosa Nasal/metabolismo , Mucosa Nasal/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Ratones , Cavidad Nasal/efectos de los fármacos , Cavidad Nasal/metabolismo , Polilisina/química , Polilisina/análogos & derivados , Natación , Masculino , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/patología , Depuración Mucociliar/efectos de los fármacos , Microglía/efectos de los fármacos , Microglía/metabolismo , HumanosRESUMEN
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly characterized by deficient sociability and repetitive behaviors. Effective treatment for the core symptoms of ASD is still lacking. Behavioral interventions show limited effectiveness, while pharmacotherapy focuses on the amelioration of secondary symptomatology. Oxytocin (OXT) is a neuropeptide known for its prosocial impact, making it a candidate drug for ASD treatment. Its alleviating effect has been and still is widely researched, but outcomes reported by clinical studies are ambiguous. We examined the effect of daily intranasal OXT (0.8 IU/kg) administration for 4 weeks on the ASD-like phenotype in Shank3-/- adult mice. Animals treated with OXT spent twice as much time interacting with the social partner as early as after 2 weeks of treatment. Furthermore, OXT-treated mice exhibited reduced explorative behavior by 50%, after 4 weeks of treatment, and a 30% reduction in repetitive behavior, 4 weeks after treatment termination. One-fold higher sociability and 30% reduced exploration due to OXT lasted up to 4 weeks following the treatment termination. However, social disinterest was elevated by roughly 10% as well, indicating a form of social ambivalence. Obtained results support the therapeutic potential of intranasally administered OXT in alleviating social shortfalls in a genetic model of ASD. Subsequent research is necessary to elucidate the benefits and risks of the long-term OXT administration, as well as its applicability in other ASD models and the potential treatment effect on social communication, which was not measured in the present study.
Asunto(s)
Administración Intranasal , Trastorno del Espectro Autista , Modelos Animales de Enfermedad , Ratones Noqueados , Oxitocina , Conducta Social , Animales , Oxitocina/administración & dosificación , Oxitocina/farmacología , Administración Intranasal/métodos , Ratones , Masculino , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/genética , Proteínas del Tejido Nervioso/genética , Trastorno Autístico/genética , Trastorno Autístico/tratamiento farmacológico , Conducta Exploratoria/efectos de los fármacos , Proteínas de Microfilamentos/genética , Conducta Animal/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
El Trastorno Depresivo Mayor es la causaprincipal de discapacidad a nivel mundial. La depresión resistente al tratamiento ocurre en un subgrupo de pacientes con trastorno depresivo mayor, y consiste en una falta de respuesta a dos o más antidepresivos diferentes en dosis y duración adecuadas, con una adherencia óptima al tratamiento. En 2019 tanto la FDA como la EMA aprobaron la indicación de esketamina intranasal (esketamina in-) en el Trastorno Depresivo Mayor, cuyo mecanismo de acción se basa en el antagonismo del receptor NMDA. En este artículo exponemos el caso de una paciente con Trastorno Depresivo Mayor, que fue tratada con esketamina en uso compasivo, los efectos secundarios presentados y el manejo de los mismos. Los resultados fueron espectaculares, ya que, a partir de la tercera administración, se observó una respuesta clínica muy favorable, evidenciándose la remisión completa a las 5 semanas. El uso de esketamina intranasal ha demostrado ser muy efectivo y con una gran rapidez de acción, siendo el único antidepresivo capaz de lograr la remisión completa en esta paciente tan compleja y grave, además de conseguir ajustar a la baja la medicación concomitante. Los efectos secundarios fueron de fácil manejo, transitorios y autolimitados al momento de la administración. Tal y como se describe en la ficha técnica y en el informe de posicionamiento terapeútico de esketamina intranasal, el tratamiento debe ser administrado en un entorno clínico adecuado, que podría ser bien el hospital o el ambulatorio, ya que ambos contienen los recursos necesarios para la sesión de administración y posterior periodo de observación del paciente. (AU)
Mayor depressive disorder is the main cause of disability in the world. Treatment resistant depression occurs in a subgroup of patients with mayor depressive disorder and consists of a lack of response to two or more different antidepressants in adequate doses and duration, with optimal adherence to treatment. In 2019, both the FDA and the EMA approved the indication of intranasal esketamine in Major Depressive Disorder, whose mechanism of action is based on NMDA receptor antagonism. In this article we present the case of a patient with Major Depressive Disorder, who was treated with esketamine in compassionate use, secondary effects presented and their management. The results were dramatic, since from the third administration a very favorable clinical response was observed, showing complete remission at five weeks. The use of intranasal esketamine has proved to be very effective and rapid over time, being the only antidepressant able of achieving complete remission in this very complex and severe patient, in addition to achieving downward adjustment of the concomitant medication. The treatment may be administered in a suitable clinical environment, so both hospital and outpatient resources may be suitable places for administration. (AU)
Asunto(s)
Humanos , Administración Intranasal/métodos , Depresión/terapia , Antidepresivos/uso terapéuticoRESUMEN
La rinitis alérgica ha ido en aumento en los países latinoamericanos, dando lugar a una creciente población de pacientes que necesitan tratamiento médico para esta afección respiratoria. Su similitud con la COVID-19 en cuanto a síntomas y la posibilidad de concurrencia con esta, hacen que la rinitis alérgica sea de particular interés para los sistemas de salud. Los países de América Latina y el Caribe han sido particularmente vulnerables por múltiples desafíos, entre estos, las altas tasas de pobreza, el acceso limitado a la atención médica y las limitaciones en la prestación de servicios básicos de salud, así como la ausencia de guías de tratamiento para la rinitis alérgica en situación de pandemia. Con el objetivo de proporcionar orientación esencial para los equipos multidisciplinarios de América Latina y el Caribe con respecto a la evaluación y el tratamiento de la rinitis alérgica durante la pandemia de COVID-19, se revisó literatura científica publicada sobre tratamiento de la rinitis alérgica y COVID-19, y se consideró la opinión de profesionales líderes de sociedades científicas de la región. Se analizaron las diferentes medidas para evitar contagios, y las diferentes estrategias de tratamiento con énfasis en la terapia intranasal y el tratamiento con vacunas contra la alergia. Se formuló una declaración de posicionamiento con la intención de mantener la continuidad del servicio médico en el contexto de una pandemia y minimizar la propagación, infección y complicación asociada con el coronavirus tipo 2 del síndrome respiratorio agudo severo en pacientes con seguimiento o comenzando tratamiento para la rinitis alérgica(AU)
Allergic rhinitis has been increasing in Latin American countries, leading to a growing population of patients who need medical treatment for this respiratory condition. Its similarity to COVID-19 in terms of symptoms and the possibility of concurrence with it, make allergic rhinitis of particular interest to health systems. The countries of Latin America and the Caribbean have been particularly vulnerable due to multiple challenges, including high poverty rates, limited access to medical care and limitations in the provision of basic health services, as well as the absence of guidelines of treatment for allergic rhinitis in a pandemic situation. With the aim of to provide essential management for multidisciplinary teams in Latin America and the Caribbean regarding the evaluation and treatment of allergic rhinitis during the COVID-19 pandemic, published scientific literature on the treatment of allergic rhinitis and COVID-19 was reviewed, and the opinion of leading professionals from scientific societies in the region was considered. The different measures to avoid infections and the different treatment strategies were analyzed, with an emphasis on intranasal therapy and treatment with allergy vaccines. A position statement was formulated with the intention of maintaining continuity of medical service in the context of a pandemic and minimizing the spread, infection and complication associated with severe acute respiratory syndrome coronavirus 2 in patients undergoing or starting treatment for allergic rhinitis(AU)
Asunto(s)
Humanos , Masculino , Femenino , Administración Intranasal/métodos , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica/epidemiología , Vacunas contra la COVID-19/uso terapéutico , Región del Caribe , COVID-19/epidemiología , América LatinaRESUMEN
Effective vaccines are essential for the control of the coronavirus disease 2019 (COVID-19) pandemic. Currently developed vaccines inducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-antigen-specific neutralizing antibodies (NAbs) are effective, but the appearance of NAb-resistant S variant viruses is of great concern. A vaccine inducing S-independent or NAb-independent SARS-CoV-2 control may contribute to containment of these variants. Here, we investigate the efficacy of an intranasal vaccine expressing viral non-S antigens against intranasal SARS-CoV-2 challenge in cynomolgus macaques. Seven vaccinated macaques exhibit significantly reduced viral load in nasopharyngeal swabs on day 2 post-challenge compared with nine unvaccinated controls. The viral control in the absence of SARS-CoV-2-specific NAbs is significantly correlated with vaccine-induced, viral-antigen-specific CD8+ T cell responses. Our results indicate that CD8+ T cell induction by intranasal vaccination can result in NAb-independent control of SARS-CoV-2 infection, highlighting a potential of vaccine-induced CD8+ T cell responses to contribute to COVID-19 containment.
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Administración Intranasal/métodos , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Linfocitos T CD8-positivos/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/inmunología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Vacunación/métodos , Animales , COVID-19/epidemiología , COVID-19/virología , Vacunas contra la COVID-19/inmunología , Chlorocebus aethiops , Proteínas de la Envoltura de Coronavirus/inmunología , Proteínas M de Coronavirus/inmunología , Proteínas de la Nucleocápside de Coronavirus/inmunología , Modelos Animales de Enfermedad , Femenino , Macaca fascicularis , Masculino , Pandemias/prevención & control , Fosfoproteínas/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Resultado del Tratamiento , Células Vero , Carga ViralRESUMEN
The inflammasome NOD-like receptor (NLR) family, the pyrin domain containing 3 (NLRP3) is closely associated with exacerbation of asthma as endotoxin (lipopolysaccharide, LPS) is one of its activators present in the environment. Present study is undertaken to investigate anti-inflammatory effects of a well known phytochemical, curcumin, which might regulate LPS exposed asthma exacerbations by modulating NLRP3 activation if given through intranasal route. Balb/c mice were sensitized with intraperitoneal injection of OVA (Ovalbumin; 100 µg of OVA with alum) from day 1 to 8 and exposed to LPS with 1% OVA aerosol from day 9 to 15. LPS (0.1 µg) was given an hour before sensitization and OVA-aerosol challenge. Significant decrease in inflammatory cell recruitment and restoration of structural changes in lungs, alterations in mRNA and protein expressions of TLR-4, NF-κB, NLRP3, Caspase-1, IL-1ß, MMP-9, IL-5 and IL-17 in intranasal curcumin alone and corticosteroid combined pretreatment group.
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Asma/tratamiento farmacológico , Curcumina/farmacología , Dexametasona/farmacología , Inflamasomas/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Administración Intranasal/métodos , Animales , Asma/inducido químicamente , Asma/metabolismo , Caspasa 1/metabolismo , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Ovalbúmina/farmacología , Factor de Transcripción ReIA/metabolismoRESUMEN
Asthma being an inflammatory disease of the airways lead to structural alterations in lungs which often results in the severity of the disease. Curcumin, diferuloylmethane, is well known for its medicinal properties but its anti-inflammatory potential via Histone deacetylase inhibition (HDACi) has not been revealed yet. Therefore, we have explored here, anti-inflammatory and anti-fibrotic potential of intranasal curcumin via HDAC inhibition and compared its potential with Sodium butyrate (SoB), a known histone deacetylase inhibitor of Class I and II series. Anti-inflammatory potential of SoB, has been investigated in cancer but not been studied in asthma before. MATERIALS AND METHODS: In present study, ovalbumin (OVA) was used to sensitize Balb/c mice and later exposed to (1%) OVA aerosol. Curcumin (5 mg/kg) and Sodium butyrate (50 mg/kg) was administered through intranasal route an hour before OVA aerosol challenge. Efficacies of SoB and Curcumin as HDAC inhibitors were evaluated in terms of different inflammatory parameters like, total inflammatory cell count, reactive oxygen species (ROS), histamine release, nitric oxide and serum IgE levels. Inflammatory cell recruitment was analyzed by H&E staining and structural alterations were revealed by Masson's Trichrome staining of lung sections. RESULTS: Enhanced Matrix Metalloproteinase-2 and 9 (MMP-2 and MMP-9) activities were observed in bronchoalveolar lavage fluid (BALF) of asthmatic mice by gelatin zymography which was inhibited in both treatment groups. Protein expressions of MMP-9, HDAC 1, H3acK9 and NF-kB p65 were modulated in intranasal curcumin and SoB pretreatment groups. CONCLUSION: This is the first report where intranasal curcumin inhibited asthma severity via affecting HDAC 1 (H3acK9) leading to NF-kB suppression in mouse model of allergic asthma.
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Asma/dietoterapia , Ácido Butírico/administración & dosificación , Curcumina/administración & dosificación , Inhibidores de Histona Desacetilasas/administración & dosificación , Inflamación/dietoterapia , Pulmón/efectos de los fármacos , Administración Intranasal/métodos , Animales , Antiinflamatorios/administración & dosificación , Asma/metabolismo , Líquido del Lavado Bronquioalveolar/química , Modelos Animales de Enfermedad , Fibrosis/dietoterapia , Fibrosis/metabolismo , Inmunoglobulina E/metabolismo , Inflamación/metabolismo , Pulmón/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/farmacologíaRESUMEN
BACKGROUND: Anesthesia studies using high-flow, humidified, heated oxygen delivered via nasal cannulas at flow rates of more than 50 l · min-1 postulated a ventilatory effect because carbon dioxide increased at lower levels as reported earlier. This study investigated the increase of arterial partial pressure of carbon dioxide between different flow rates of 100% oxygen in elective anesthetized and paralyzed surgical adults before intubation. METHODS: After preoxygenation and standardized anesthesia induction with nondepolarizing neuromuscular blockade, all patients received 100% oxygen (via high-flow nasal oxygenation system or circuit of the anesthesia machine), and continuous jaw thrust/laryngoscopy was applied throughout the 15-min period. In this single-center noninferiority trial, 25 patients each, were randomized to five groups: (1) minimal flow: 0.25 l · min-1, endotracheal tube; (2) low flow: 2 l · min-1, continuous jaw thrust; (3) medium flow: 10 l · min-1, continuous jaw thrust; (4) high flow: 70 l · min-1, continuous jaw thrust; and (5) control: 70 l · min-1, continuous laryngoscopy. Immediately after anesthesia induction, the 15-min apnea period started with oxygen delivered according to the randomized flow rate. Serial arterial blood gas analyses were drawn every 2 min. The study was terminated if either oxygen saturation measured by pulse oximetry was less than 92%, transcutaneous carbon dioxide was greater than 100 mmHg, pH was less than 7.1, potassium level was greater than 6 mmol · l-1, or apnea time was 15 min. The primary outcome was the linear rate of mean increase of arterial carbon dioxide during the 15-min apnea period computed from linear regressions. RESULTS: In total, 125 patients completed the study. Noninferiority with a predefined noninferiority margin of 0.3 mmHg · min-1 could be declared for all treatments with the following mean and 95% CI for the mean differences in the linear rate of arterial partial pressure of carbon dioxide with associated P values regarding noninferiority: high flow versus control, -0.0 mmHg · min-1 (-0.3, 0.3 mmHg · min-1, P = 0.030); medium flow versus control, -0.1 mmHg · min-1 (-0.4, 0.2 mmHg · min-1, P = 0.002); low flow versus control, -0.1 mmHg · min-1 (-0.4, 0.2 mmHg · min-1, P = 0.003); and minimal flow versus control, -0.1 mmHg · min-1 (-0.4, 0.2 mmHg · min-1, P = 0.004). CONCLUSIONS: Widely differing flow rates of humidified 100% oxygen during apnea resulted in comparable increases of arterial partial pressure of carbon dioxide, which does not support an additional ventilatory effect of high-flow nasal oxygenation.
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Administración Intranasal/métodos , Apnea/sangre , Apnea/terapia , Dióxido de Carbono/sangre , Terapia por Inhalación de Oxígeno/métodos , Administración Intranasal/efectos adversos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno/efectos adversos , Presión ParcialAsunto(s)
Administración Intranasal/métodos , COVID-19/prevención & control , COVID-19/transmisión , Administración Intranasal/tendencias , Antivirales/administración & dosificación , COVID-19/terapia , Humanos , Receptores Virales/efectos de los fármacos , Receptores Virales/metabolismo , SARS-CoV-2/patogenicidadRESUMEN
Natural polysaccharides have shown promising effects on the regulation of immunity in animals. In this study, we examined the immune stimulatory effect of intranasally administered Codium fragile polysaccharides (CFPs) in mice. Intranasal administration of CFPs in C57BL/6 mice induced the upregulation of surface activation marker expression in macrophages and dendritic cells (DCs) in the mediastinal lymph node (mLN) and the production of interleukin-6 (IL-6), IL-12p70, and tumor necrosis factor-α in bronchoalveolar lavage fluid. Moreover, the number of conventional DCs (cDCs) was increased in the mLNs by the upregulation of C-C motif chemokine receptor 7 expression, and subsets of cDCs were also activated following the intranasal administration of CFP. In addition, the intranasal administration of CFPs promoted the activation of natural killer (NK) and T cells in the mLNs, which produce pro-inflammatory cytokines and cytotoxic mediators. Finally, daily administration of CFPs inhibited the infiltration of Lewis lung carcinoma cells into the lungs, and the preventive effect of CFPs on tumor growth required NK and CD8 T cells. Furthermore, CFPs combined with anti-programmed cell death-ligand 1 (PD-L1) antibody (Ab) improved the therapeutic effect of anti-PD-L1 Ab against lung cancer. Therefore, these data demonstrated that the intranasal administration of CFP induced mucosal immunity against lung cancer.
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Adyuvantes Inmunológicos/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma Pulmonar de Lewis/inmunología , Carcinoma Pulmonar de Lewis/terapia , Chlorophyta/química , Inmunidad Mucosa , Inmunoterapia/métodos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Fitoterapia/métodos , Extractos Vegetales/administración & dosificación , Polisacáridos/administración & dosificación , Administración Intranasal/métodos , Animales , Linfocitos T CD8-positivos/inmunología , Carcinoma Pulmonar de Lewis/patología , Línea Celular Tumoral , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Femenino , Células Asesinas Naturales/inmunología , Neoplasias Pulmonares/patología , Activación de Linfocitos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BLRESUMEN
The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989-1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment.