Polymeric nanocarriers for nose-to-brain drug delivery in neurodegenerative diseases and neurodevelopmental disorders

Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system (CNS) and result in their damage and death. Neurodevelopmental disorders include intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes. The treatment of neurodegenerative and neurodevelopmental conditions, together affecting ∼120 million people worldwide, is challenged by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS. The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions. This pathway is more efficient for nanoparticles than for solutions, hence, the research on intranasal nano-drug delivery systems has grown exponentially over the last decade. Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility. This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions, the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them. Then, a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.

Tratamiento de la rinitis alérgica en época de pandemia. Documento de consenso de sociedades médicas de América Latina y el Caribe / Treatment of allergic rhinitis in pandemic times. Consensus statement from medical societies of Latin America and the Caribbean

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)

Effect of intranasal administration of NeuroEPO in the histological structure of the olfactory mucosa of Wistar rats / Efecto de la administración intranasal de NeuroEPO en la estructura histológica de la mucosa olfatoria de ratas Wistar

Introduction: Strokes and neurodegenerative diseases are major global health problems, not only because they cause high mortality and disability, but due to the lack of effective therapies. NeuroEPO, a variant of recombinant human erythropoietin (rHu-EPO) with a low sialic acid content, has shown encouraging results as a potential neuroprotective agent when administered intranasally. Objective: To determine the effect of intranasal administration of NeuroEPO on the histological structure of the olfactory mucosa of Wistar rats. Materials and Methods: An experimental, prospective, and longitudinal study was conducted on Wistar rats. Ten healthy animals were randomly distributed into two groups of five each. The control group received a vehicle (0.3 μl/g/day) and the treated group received NeuroEPO (300 μg/kg/day). Both treatments were administered intranasally for 28 days. The histological characteristics of the olfactory mucosa were evaluated. The medians between the study groups were compared using the Mann-Whitney U test. Results: There were no alterations in the histological characteristics of the olfactory epithelium. However, slight hypertrophy and hyperplasia of the Bowman's glands were observed at the level of the lamina propria in the group treated with NeuroEPO. Conclusions: The administration of the nasal formulation of NeuroEPO did not induce histological alterations of the olfactory mucosa of Wistar rats under the experimental conditions of this research.

Introducción: Los accidentes cerebrovasculares y las enfermedades neurodegenerativas constituyen un importante problema de salud mundial. No solo porque causan una alta mortalidad y discapacidad, sino por la falta de terapias eficaces para tratarlos. La NeuroEPO, una variante de la eritropoyetina humana recombinante (rHu-EPO) con bajo contenido en ácido siálico, ha mostrado resultados alentadores como potencial agente neuroprotector al ser administrada por vía intranasal. Objetivo: Determinar el efecto de la administración intranasal de NeuroEPO en la estructura histológica de la mucosa olfatoria de ratas Wistar. Materiales y Métodos: Se realizó un estudio experimental, prospectivo y de corte longitudinal en ratas Wistar. Se utilizaron diez animales sanos distribuidos aleatoriamente en dos grupos de cinco cada uno. El grupo control recibió vehículo (0,3 μl/g/día) y el grupo tratado recibió NeuroEPO (300 μg/kg/día). Ambos tratamientos fueron administrados por vía intranasal durante 28 días. Fueron evaluadas las características histológicas de la mucosa olfatoria. Las medianas de los grupos del estudio fueron comparadas mediante la prueba U de Mann-Whitney. Resultados: No se evidenciaron alteraciones en las características histológicas del epitelio olfatorio. Sin embargo, a nivel de la lámina propia en el grupo tratado con NeuroEPO, se observó una ligera hipertrofia e hiperplasia de las glándulas de Bowman. Conclusiones: La administración de la formulación nasal de NeuroEPO no indujo alteraciones histopatológicas de la mucosa olfatoria de ratas Wistar en las condiciones experimentales de esta investigación.

The anti-glioma effects of borneol and RGD co-modified docetaxel loaded nanoparticles after intranasal administration / 药学学报

Borneol (Bo) and Arg-Gly-Asp (RGD) co-modified docetaxel (DTX) loaded MPEG-PLGA nanoparticles (DTX-Bo-RGD-NPs) were prepared to improve the therapeutic effect of DTX against glioma after intranasal administration. DTX-Bo-RGD-NPs were prepared by emulsification-solvent evaporation method, and their morphology, particle size, zeta potential, drug loading capacity (DLC), stability, and in vitro release properties were investigated. The fluorescence probe coumarin-6 loaded NPs were prepared for investigating the NPs' uptake property on C6 and 16HBE cell models to evaluate in vitro targeting ability. The DiR loaded NPs were prepared for observing the fluorescence intensity at the brain tumor site after intranasal administration through in vivo imaging system in a C6 rat orthotropic model, evaluating the targeting ability in vivo. The anti-tumor effects of DTX-Bo-RGD-NPs were also investigated in such C6 rat orthotropic model in vivo. Animal welfare and experimental procedures are in compliance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine. The results showed that DTX-Bo-RGD-NPs were spherical and uniformly distributed, with a particle size of about 140 nm and a zeta potential of -20 to -30 mV. The drug delivery system showed good stability and sustained release property in vitro, and favorable brain tumor targeting effect in vitro and in vivo. Such novel drug delivery system significantly improved the accumulation of DTX-Bo-RGD-NPs in tumor sites and displayed a higher brain tumor targeting efficiency, providing promising therapeutics of DTX for the treatment of glioma after intranasal administration.

Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of

The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of

Dexmedetomidina intranasal en sedación para ginecoobstetricia / Intranasal dexmedetomidine in sedation for OB/GYN

Objetivos: evaluar el uso de la dexmedetomidina intranasal como coadyuvante para sedación en LUI y AMEU asociado al sistema de infusión controlado por objetivo. Métodos: ensayo clínico no controlado, prospectivo y simple ciego. Muestra de 48 pacientes que cumplen los criterios de inclusión. Grupo CD se administró Dexmedetomidina IN a dosis de 0,9 µg/kg y otro grupo de control. Para el análisis estadístico de variables continuas se usó media y DE; para variables ordinales se calculó frecuencia. Además de prueba T de Student y Chi χ2. Nivel de confianza de 95 % y margen de error 12%. Resultados: edad media de 32 ± 7 años; en el grupo CD la dosis de inducción y mantenimiento de remifentanil fue de 2 ± 0,7 ng/ml y en el grupo SD la dosis de inducción fue de 4,1 ± 0,7 ng/ml y de mantenimiento 3,9 ± 0,5 ng/ml; para el propofol la dosis de inducción y mantenimiento fue 3,7 ± 0,5 mcg/ml en el grupo SD mientras que, en el grupo CD la dosis de inducción y mantenimiento fue de 2,1 ± 0,5 mcg/ml. La frecuencia cardiaca de 64 - 62 y en el grupo SD fue de 70 - 67 latidos/min. La PAM asociado al dexme está por 73 mmHg y el grupo de SD es de 78 mmHg. No se verifico complicaciones por la administración de la Dexmedetomidina. Conclusiones: la dexmedetomidina IN permite disminuir la dosis de los fármacos, con estabilidad de los cambios hemodinámicos, la dosis utilizada no produce complicaciones.

Objectives: to evaluate the use of intranasal dexmedetomidine as an adjunct for sedation in LUI and AMEU associated with the objective controlled infusion system. Methods: uncontrolled, prospective, single-blind clinical trial. Sample of 48 patients who meet the inclusion criteria. Group CD was administered Dexmedetomidine IN a dose of 0.9 µg / kg and another control group. For the statistical analysis of continuous variables, mean and SD were used; For ordinal variables, frequency was calculated. In addition to Student's T-test and Chi χ2. 95% confidence level and 12% margin of error. Results: age of 32 ± 7 years; in the CD group the induction and maintenance dose of remifentanil was 2 ± 0.7 ng / ml and in the SD group the induction dose was 4.1 ± 0.7 ng / ml and maintenance dose 3.9 ± 0.5 ng / ml; for propofol the induction and maintenance dose was 3.7 ± 0.5 mcg / ml in the SD group, while in the CD group the induction and maintenance dose was 2.1 ± 0.5 mcg / ml. The heart rate was 64-62 and in the SD group it was 70-67 beats / min. The MAP associated with dexme is 73 mmHg and the SD group is 78 mmHg. No complications were verified by the administration of Dexmedetomidine. Conclusions: dexmedetomidine IN allows to decrease the dose of drugs, with stability of hemodynamic changes, the dose used does not cause complications.

Investigation of Corchorus olitorius mucilage as a potential mucoadhesive agent in developing in situ mucoadhesive nasal gel

The present study aimed to formulate a mucoadhesive in situ gel with mucilage extracted from Corchorus olitoriusfor the intranasal route. Propranolol HCl used as a model drug. For the comparative study, the mucoadhesive in situgels were prepared using two different concentration 0.4% and 0.5% of C. olitorius mucilage, Carbopol P-934 andhydroxypropyl methylcellulose. The prepared in situ gel was subjected to characterization test, such as pH, appearance,gelation temperature, spreadability, viscosity, mucoadhesive strength, and in vitro study. From the comparative study,0.5% mucilage containing in situ gel formulation can be considered as optimum formulation.

Meta-analysis of Efficacy and Safety of Intranasal Administration of Dexmedetomidine versus Oral Administration of Chloral Hydrate for Programmed Sedation in Children / 中国药房

OBJECTIVE：To systematically evaluat e the efficacy and safety of intranasal administration of dexmedetomidine versus oral administration of chloral hydrate for programmed sedation in children. METHODS ：Retrieved from Cochrane Library ，PubMed， Embase，CBM，CNKI and Wanfang database ，randomized controlled trials （RCTs）about intranasal administration of dexmedetomidine （trial group ）versus oral administration of chloral hydrate （control group ）for programmed sedation in children were collected. Cochrane 5.1.0 bias risk assessment tool was used to evaluate the quality of the included literatures after literature screening and data extraction，and Meta-analysis was conducted by using Rev Man 5.3 statistical software. RESULTS ：A total of 8 RCTs were included ， with a total of 1 413 children. Meta-analysis showed that the sedation success rate [RR ＝1.13，95％CI（1.02，1.25），P＝0.02]，sedation onset time [MD ＝－1.07，95％CI（－1.82，－0.31），P＝0.006]，sedation duration [MD ＝－8.25，95％CI（－14.02，－2.47），P＝ 0.005]，wake-up time [MD ＝－9.63，95％CI（－15.40，－3.86），P＝0.001]，the incidence of nausea and vomiting [RR ＝0.05，95％CI （0.02，0.14），P＜0.000 01] in the trial group were significantly better than those in control group. There was no statistical significance in the incidence of SpO 2＜95％ [RR＝0.60，95％CI（0.24，1.54），P＝0.29]，incidence of hypotension [RR ＝1.18，95％CI（0.51， 2.74），P＝0.71]，incidence of bradycardia [RR ＝1.33，95％CI（0.18，9.88），P＝0.78] between 2 groups. CONCLUSIONS ：Intranasal administration of dexmedetomidine has better efficacy than oral administration of chloral hydrate for programmed sedation in children with good safety.

Postoperative Management of Eosinophilic Chronic Rhinosinusitis with Nasal Polyps: Impact of High-Dose Corticosteroid Nasal Spray

Abstract Introduction Eosinophilic chronic rhinosinusitis (ECRS) is characterized by an eosinophilic inflammation driven by Th2-type cytokines. Glucocorticosteroids are the most common first-line treatment for ECRS with nasal polyps. Objective We have evaluated the long-term treatment with double-dose intranasal corticosteroids in refractory ECRS nasal polyps resistant to the conventional dose and assessed the risk of adverse systemic effects Methods Sixteen subjects were enrolled in this study. All subjects had ECRS after endoscopic sinus surgery that resulted in recurrentmild andmoderate nasal polyps and were undergoing a postoperative follow-up application of mometasone furoate at a dose of 2 sprays (100 μg) in each nostril once a day (200 μg). All the patients were prescribed mometasone furoate, administered at a dose of 2 sprays (100 μg) in each nostril twice a day (400 μg) for 6 months. Results The average scores of the symptoms during the regular dose of intranasal steroid treatment were 5.2 ± 2.2, but 6 months after the high-dose application, they had significantly decreased to 2.5 ± 1.4 (p < 0.05). The polyp size showed an average score of 1.38 during the regular dose which was significantly reduced to 0.43 (p < 0.01) by the double dose. Glycated hemoglobin (HbA1c) showed normal ranges in all the patients tested. The cortisol plasma concentration was also normal. Conclusion Doubling the dose of the nasal topical spray mometasone furoate might be recommended for the treatment of recurrent nasal polyps in the postoperative follow-up of intractable ECRS. (AU)

Intranasal Treatment With 1, 25-Dihydroxyvitamin D3 Alleviates Allergic Rhinitis Symptoms in a Mouse Model

PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.

Research progress on non-injection administration systems of paclitaxel / 中草药

Paclitaxel (PTX) is a complex secondary metabolite isolated from Taxus brevifolia, which widely used as chemotherapentic agent with a broad spectrum of actinity against cancer in the world. Its water solubility was poor and oral bioavailability was low. Cremophor-EL was used in traditional PTX injections to improve the solubility of PTX, and resulted in several adverse side effects such as severe hypersensitivity. Pre-desensitization treatment was needed before clinical use. Recently, a variety of non-injection drug delivery systems (DDS) of PTX have been developed. In this paper, the research progress of non-parenteral PTX was reviewed, including oral administration systems, vaginal administration systems, transdermal DDS, implantable DDS, transdermal DDS, intranasal administration and inhalation DDS, so as to provide references for future study and clinical applications.

Patient with Recurrent Glioblastoma Responding Favorably to Ketogenic Diet Combined with Intranasal Delivery of Perillyl Alcohol: A Case Report and Literature Review

Introduction Monoterpene perillyl alcohol (POH) is cytotoxic to temozolomideresistant glioma cells, regardless of its O6-methylguanine-methyltransferase (MGMT) promoter methylation status. Moreover, adherence to a ketogenic diet (KD) produced successful outcomes in preclinical and clinical studies in the glioma setting. Case Presentation A 54-year-old Caucasian man had a confirmed diagnosis of refractory glioblastoma multiforme (GBM). The immunohistochemical evaluation was negative for methylation, and failed to detect mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes. In January 2016, the patient was enrolled in a clinical trial combining daily intranasal delivery of POH in combination with a KD. The KD was administered concomitantly with inhalation of POH (55 mg, 4 times a day) in an uninterrupted administration schedule for 3 months. Results The combination treatment was well-tolerated. The nutritional status and anthropometric measurements of the patient were measured. Adherence to the KD was confirmed by measuring the levels of ketone bodies in the urine. Throughout the treatment, a reduced frequency of seizures was observed. After three months of adherence to the treatment, the patient presented with weight loss, reduced body fat, increased water retention, and a slight increase in bone and muscle mass. A follow-up magnetic resonance imaging (MRI) scan after 3 months of treatment revealed marked reduction of the enhancing lesion. Conclusion Intranasal delivery of POH combined with concomitant adherence to a KD appeared to have a beneficial therapeutic effect in a patient with recurrent GBM. Further studies are needed to evaluate the efficacy of this therapeutic strategy in a larger cohort of treatment-refractory GBM patients.

Introdução O monoterpeno álcool perílico (AP) é citotóxico para linhagens celulares de glioblastoma, independentemente do status do promotor de metilação O6-metilguaninametiltransferase (MGMT). Além disso, a adesão à dieta cetogênica (DC) produziu resultados bem sucedidos em desenho de estudos pré-clínicos e clínicos de glioma. Relato de Caso Homem, 54 anos, caucasiano, com diagnóstico de glioblastoma multiforme (GBM) recidivo. A avaliação imuno-histoquímica foi negativa para metilação e não detectou mutações do gene da isocitrato desidrogenase 1 e 2 (IDH1 IDH2). Em janeiro de 2016, o paciente foi inscrito em um ensaio clínico da administração intranasal diária do AP combinada a DC. A DC foi administrada concomitantemente com inalação de AP (55 mg, 4 vezes ao dia) em um cronograma de administração ininterrupto durante 3 meses. Resultados O tratamento combinado foi bem tolerado. O estado nutricional e as medidas antropométricas do paciente foram avaliadas. Aderência a DC foi confirmada pela presença de corpos cetônicos na urina. Ao longo do tratamento, observou-se redução da frequência de convulsões. Após três meses de adesão ao tratamento, o paciente apresentou perda de peso, redução da gordura corporal, melhor hidratação e um aumento discreto da massa óssea e muscular. O acompanhamento da ressonância magnética após 3 meses de tratamento revelou redução acentuada do volume da lesão. Conclusão A administração intranasal do AP combinada a DC sugere ter um efeito terapêutico benéfico em pacientes com GBM recorrente. São necessários mais estudos para avaliar a eficácia desta estratégia terapêutica em uma coorte maior de pacientes com GBM refratários.

Intranasal Administration of Interleukin-1 Receptor Antagonist in a Transient Focal Cerebral Ischemia Rat Model

The interleukin-1 receptor antagonist (IL-1RA) is a potential stroke treatment candidate. Intranasal delivery is a novel method thereby a therapeutic protein can be penetrated into the brain parenchyma by bypassing the blood-brain barrier. Thus, this study tested whether intranasal IL-1RA can provide neuroprotection and brain penetration in transient cerebral ischemia. In male Sprague-Dawley rats, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h. The rats simultaneously received 50 mg/kg human IL-1RA through the intranasal (IN group) or intraperitoneal route (IP group). The other rats were given 0.5 mL/kg normal saline (EC group). Neurobehavioral function, infarct size, and the concentration of the administered human IL-1RA in the brain tissue were assessed. In addition, the cellular distribution of intranasal IL-1RA in the brain and its effect on proinflammatory cytokines expression were evaluated. Intranasal IL-1RA improved neurological deficit and reduced infarct size until 7 days after MCAO (p<0.05). The concentrations of the human IL-1RA in the brain tissue 24 h after MCAO were significantly greater in the IN group than in the IP group (p<0.05). The human IL-1RA was confirmed to be co-localized with neuron and microglia. Furthermore, the IN group had lower expression of interleukin-1β and tumor necrosis factor-α at 6 h after MCAO than the EC group (p<0.05). These results suggest that intranasal IL-1RA can reach the brain parenchyma more efficiently and provide superior neuroprotection in the transient focal cerebral ischemia.

Effects of dexmedetomidine by the intranasal route on the stress response during tracheal extubation after gynecological surgery / 临床麻醉学杂志

Objective To explore the influence of dexmedetomidine for nasal administration by three different concentrations on the stress response in patients with general anaesthesia during the peri-extubation period of gynecological surgery and to explore the optimized dosage.Methods Eighty patients undergoing general anaesthesia were randomly divided into four groups:control group (group C),and three different doses of intranasal dexmedetomidine,groups D1,D2,D3 receiving intranasal dexmedetomidine 0.6,1.2 and 1.8 μg/kg 30 min before the end of the operation,respectively.Group C was given the same volume of saline.Heart rate (HR),mean arterial pressure (MAP) and ratepressure-product (RPP) were recorded immediately after intranasal administration (T1),the end of the surgery (T2),recovery time (T3),extubation time (T4),1 min after extubation (T5),5 min after extubation (T6) and 10 min after extubation (T7).Blood samples were taken at T1,T2,T4 and T6 to detect the serum concentrations of norepinephrine (NE) and cortisol (Cor).Postoperative recovery outcomes were recorded.Results Compared with group C,MAP,HR and RPP at T3-T5 in group D1 were reduced significantly (P＜0.05).In addition,those were all decreased in groups D2 and D3 at T2-T7 (P＜0.05).Compared with group C,the serum concentrations of NE and Cor at T4 and T6 in group D1,at T2,T4 and T6 in groups D2,D3 were decreased obviously (P＜0.05).Awaken time,extubation time and PACU stay time were shortened significantly in groups C,D1 and D2 compared with group D3 (P＜0.05).Conclusion Intranasal administration of dexmedetomidine 30 min before the end of the operation could attenuate the extubation reaction and the adverse reaction of cardiovascular system during the peri-extubation period.

Clinical Observation of Intranasal Dexmedetomidine and Sufentanil for Pediatric Sedation Undergoing Stomatology Operation of Outpatient Department / 中山大学学报(医学科学版)

[Objective] To research the sedative effect of intranasal dexmedetomidine and sufentanil for pediatric sedation for stomatological operation of outpatient department.[Methods] 60 children undergoing stomatological operation of outpatient department,age 3 ～ 7 years,weighing 10 ～ 32 kg,of ASA physical status Ⅰ ～ Ⅱ,were divided into the three groups (n =20) randomly using a random number table:group dexmedetomidine and sufentanil (group DS),group dexmetomidine (group D),group sufentanil (group S).Recorded the children's behavior using the Ohio State University behavior rating score (OSUBRS),the University of Michigan Sedation Score (UMSS),SBP,HR and side-effects when entry,during and leave operation and in post-anesthesia care unit,side-effects,the satisfaction of stomatological doctors and parents.[Results] The OSUBRS of group DS when entry,during operation were lower than group D (P ＜ 0.01).The UMSS of group DS were higher than group D and group S when entry and during operation (P ＜ 0.05).The success rate of group DS was higher than group D and group S (P ＜ 0.01).There was no different of mean percentage change in systolic blood pressure and heart rate from baseline between group DS and group D (P ＞ 0.05).There were no instances of respiratory depression,hypotension and bradycadia.[Conclusion] Intranasal dexmedetomidine and sufentanil provides satisfactory pediatric sedation for stomatological operation of outpatient department without side effects such as respiratory depression,bradycadia and hypotension.

Effect of salvianolic acid B by intranasal administration on cognitive function and neurogenesis of cerebral ischemia rats / 中草药

Objective: To study the concentration of salvianolic acid B (Sal B) in rat hippocampus after intranasal administration, and to inveategate the improvement on cognitive dysfunction of rats with cerebral ischemic treated by intranasal administration of Sal B and its mechnisms. Methods: HPLC method was employed to check the distribution of Sal B in hippocampus by intranasal administration. Sal B was intranasal administered after one week of cerebral ischemia. The effect of Sal B by intranasal administration on cognitive dysfuctiopn was checked using Morris water maze. The effect of Sal B by intranasal administration on the hippocampus morphological characteristics was studied using Cresyl violet (Nissl) staining. BrdU injection and immunohistochemical staining were used to test the effect of Sal B on the neurogensis in hippocampus of cerebral ischemic rats. Results: After intranasal administration of Sal B, the Cmax of Sal B was (2.47 ± 0.55) μg/g, and the AUC of Sal B was (336.4 ± 73.0) μg∙min/g. Morris water maze test results showed that Sal B by intranasal administration could reduce the average escape latency of cerebral ischemic rats, increase the time in the former platform quadrant and the time of rats across the platform. Compared with the Sham group, the hippocampal CA1 cell layers were reduced and the pyramidal cells showed an irregular arrangement in the model group. Compared with model group, hippocampal morphology was clear, nerve cells arranged in regular, and the number of neurons increased significantly in groups of Sal B by intranasal administration. Immunohistochemistry results showed that the groups of Sal B by intranasal administration could increase the BrdU-positive cell number in hippocampus. Conclusion: Intranasal administration of SalB can significantly improve the distribution in the hippocampus. Intranasal administration of Sal B could improve the cognitive dysfuction, and this effect maybe related to the directive effect of Sal B on promoting neurogenesis after cerebral ischemic.

Effect of chitosan neurotoxin nanoparticles on permeability of blood brain barrier by intranasal administration / 中草药

Objective: To prepare chitosan neurotoxin nanoparticles (CS-NT-NP) and study its effect on the permeability of blood brain barrier and the serum levels of S100β by intranasal administration. Methods: A formamide extraction-ultraviolet spectrophotometry method was employed to determine the concentration of Evans blue (EB) in brain by different routes of administration and preparations. Qualitative analysis of fluorescence intensity and distribution of EB in brain tissue was performed by fluorescence microscopy. The serum S100β protein concentration was determined by ELISA. Results: Compared with the control group and NT group, CS-NT-NP could significantly increase the content of EB in the brain with time-effect relation and reached the peak at 120 min (P < 0.01); Compared with muscle injection and ip injection, intranasal administration could significantly increase the content of EB and reached peak time quickly. The results were consistent with the experimental results of qualitative analysis of fluorescence intensity and distribution of EB in brain tissue by fluorescence microscopy and S100β protein in serum. It was consistent with the experimental results of S100β protein. Conclusion: CS-NT-NP by intranasal administration can significantly increase the permeability of BBB, and further increase the drug concentration in the brain, which is a good carrier of macromolecular drugs into the brain.

Post-operative analgesic efficacy of fentanyl via different routes A comparative study of nebulisation, intranasal and intravenous routes

Background: Pain is main post operative adverse outcomes causing patient distress, prolonging hospital stay, and increasing the incidence of admissions after surgery. Study was done to assess and compare the post-operative analgesic effects of fentanyl via nebulisation, intranasal and intravenous routes to provide better analgesia, anxiolysis and sedation to the patient. Materials and methods: After approval from ethical committee of SPMC, Bikaner and written informed valid consent from patients, sixty patients of either sex belonging to ASA class I and II, were randomised into three group (Group I - Nebulised Fentanyl, Group II - Intranasal Fentanyl, Group III - Intravenous Fentanyl). With all aseptic precaution, subarachnoid block was instilated via 23/25 gauze spinal needle by injecting sufficient dose of bupivacaine heavy 5% to achieve an adequate sensory and motor block for the proposed surgery. When patient complained pain 1st time, fentanyl was given via nebulisation in group I, intranasal in group II, and intravenous in group III with dose 4 mcg/kg, 1.5 mcg/kg, 2 mcg/kg respectively. Patients were assessed for pain by VAS score. For statistical data, SPSS 10.0 software was used. Results: In present study, Ramsay sedation score, patient satisfaction score and duration of analgesia was better in group II as compared to group I and III. Group III had lesser time of onset of analgesia in comparison to group II and I respectively. Singh R, Pareek A, Kumari M, Khilji MY, Sirohiya P. Post-operative analgesic efficacy of fentanyl via different routes – A comparative study of nebulisation, intranasal and intravenous routes. IAIM, 2016; 3(6): 16-22. Page 17 Conclusion: On the basis of analgesic efficacy, we concluded that intranasal group was better than nebulisation and intravenous route.

Preparation of co-modified liposomes of α-cobrotoxin and its brain pharmacokinetics study in rats after intranasal administration / 中国药学杂志

OBJECTIVE: To investigate the brain pharmacokinetics of co-modified liposomes of α-cobrotoxin in rats after intranasal administration. METHODS: DSPE-PEG2000-Pep1 and DSPE-PEG2000-Pep2 were synthesized by Michael addition reaction. And their structures were verified by proton nuclear magnetic resonance spectroscopy (1H-NMR) and infrared spectroscopy (FTIR). Pep2(Pep1)-αCT-LP was prepared by the method of thin-film hydration and post-inserting, then its morphology, particle size, and Zeta potential were investigated. The encapsulation efficiency of liposomes was determined by ultrafiltration centrifugal method. The concentrations of αCT-LP, Pep1-αCT-LP, Pep2-αCT-LP, and Pep2(Pep1)-αCT-LP in periaqueductal gray (PAG) after intranasal administration were measured by microdialysis and the pharmacokinetical parameters were analyzed by PKSolver software. RESULTS: The structures of DSPE-PEG2000-Pep1 and DSPE-PEG2000-Pep2 were proved by 1H-NMR and FTIR. The prepared Pep2(Pep1)-αCT-LP was nearly spherical with uniform size, the mean particle size was (115.8±1.86) nm, and the Zeta potential was (-13.77±0.75) mV. Besides, the encapsulation efficiency was (32.75±1.12)%. The RESULTS ofin vivo test demonstrated that the αCT concentrations in PAG after intranasal administration of Pep2(Pep1)-αCT-LP were significantly increased compared with the groups of αCT-LP, Pep1-αCT-LP and Pep2-αCT-LP(P<0.05). Theρmax, tmax, and AUC0→∞ were (244.72±3.15) ng·mL-1, (88.01±4.19) min, (89 199.02±1 922.99) ng·min·mL-1, respectively. CONCLUSION: Pep2(Pep1)-αCT-LP can significantly increase the concentrations of αCT in periaqueductal gray, which provides a promising method for development of polypeptide agents for brain-targeting.

Access to the tracheal pulmonary pathway in small rodents / Vias de acesso traqueopulmonar em pequenos roedores

ABSTRACT The tracheal pulmonary route is used in diverse experimental models for the study of drugs, infectious agents, and diseases. In view of its importance and associated difficulties, the present article proposes to give research groups up-to-date information on techniques to access the tracheal pulmonary pathway of small rodents.

RESUMO As vias de acesso traqueopulmonar vêm sendo utilizadas em diversos modelos experimentais que estudam a ação de fármacos e agentes infecciosos, além de enfermidades. Tendo em vista a sua importância e as dificuldades associadas, o presente artigo de atualização propõe-se a dar ao pesquisador as informações necessárias para o emprego das técnicas de acesso traqueopulmonar em pequenos roedores.