Effects of Mucosal Decongestion on Nasal Aerodynamics: A Pilot Study.

OBJECTIVE: Mucosal decongestion with nasal sprays is a common treatment for nasal airway obstruction. However, the impact of mucosal decongestion on nasal aerodynamics and the physiological mechanism of nasal airflow sensation are incompletely understood. The objective of this study is to compare nasal airflow patterns in nasal airway obstruction (NAO) patients with and without mucosal decongestion and nondecongested healthy subjects. STUDY DESIGN: Cross-sectional study of a convenience sample. SETTING: Academic tertiary medical center. METHODS: Forty-five subjects were studied (15 nondecongested healthy subjects, 15 nondecongested NAO patients, and 15 decongested NAO patients). Three-dimensional models of the nasal anatomy were created from computed tomography scans. Steady-state simulations of airflow and heat transfer were conducted at 15 L/min inhalation rate using computational fluid dynamics. RESULTS: In the narrow side of the nose, unilateral nasal resistance was similar in decongested NAO patients and nondecongested healthy subjects, but substantially higher in nondecongested NAO patients. The vertical airflow distribution within the nasal cavity (inferior vs middle vs superior) was also similar in decongested NAO patients and nondecongested healthy subjects, but nondecongested NAO patients had substantially less middle airflow. Mucosal cooling, quantified by the surface area where heat flux exceeds 50 W/m2, was significantly higher in decongested NAO patients than in nondecongested NAO patients. CONCLUSION: This pilot study suggests that mucosal decongestion improves objective measures of nasal airflow, which is consistent with improved subjective sensation of nasal patency after decongestion.

[Correlation between nasal mucosal temperature change and nasal airflow perception].

The mechanism of nasal airflow perception remains little known. It is currently believed that the main mechanism for perceiving nasal patency is to activate transient receptor potential melastatin subtype 8. Computer fluent dynamics show that increased airflow and heat flux are associated with higher subjective scores. Similarly, physical measurements of the nasal cavity using a temperature probe show a correlation between the lower nasal mucosa temperature and better results. Trigeminal function detection also indirectly confirms this. This literature review aimed to explore the role of nasal mucosal temperature change in the subjective perception of nasal patency and the secondary aim was to appraise the relevant evidence about the mechanism.

Effects of adding a commercial capsaicin fertilizer on the feeding behavior of sika deer (Cervus nippon).

We investigated the inhibitory effect of capsaicin fertilizer on feeding in deer. We tested four captive adult female deer. In Experiment 1, in addition to the treatment (intact) containing only a solid feed (HC), we mixed the fertilizer not containing capsaicin (F) or the capsaicin fertilizer (CF) in the solid feed. In addition, the solid feed was put on a wire net that capsaicin fertilizer was placed 5 cm below (SCF). We investigated their feeding behavior response. In Experiment 2, we changed the amount of substance (fertilizer and capsaicin fertilizer) mixed in the HC. We mixed different amounts (0, 50, 100, and 200 g) of the treatments other than the intact with HC and presented them to the deer, and investigated their feeding behavior response. In Experiment 1, intake in the F and CF decreased (p < .05). In Experiment 2, HC intake was significantly lower in the 100 and 200 g CF (p < .05). However, HC intake relatively increased by the last day in the CF 200 g too. The capsaicin fertilizer decreased the feeding behavior of deer by directly touching the mucous membranes of the deer nose and lips. However, the effects were decreased over time.

Correlation between nasal mucosal temperature change and the perception of nasal patency: a literature review.

BACKGROUND: The mechanism of nasal airflow sensation is poorly understood. This study aimed to examine the role of nasal mucosal temperature change in the subjective perception of nasal patency and the methods by which it can be quantified. METHOD: Medline and PubMed database searches were performed to retrieve literature relevant to the topic. RESULTS: The primary mechanism producing the sensation of nasal patency is thought to be the activation of transient receptor potential melastatin family member 8 ('TRPM8'), a thermoreceptor that is activated by nasal mucosal cooling. Computational fluid dynamics studies have demonstrated that increased airflow and heat flux are correlated with better patient-reported outcome measure scores. Similarly, physical measurements of the nasal cavity using temperature probes have shown a correlation between lower nasal mucosal temperatures and better patient-reported outcome measure scores. CONCLUSION: Nasal mucosal temperature change may be correlated with the perception of improved nasal patency. Future research should quantify the impact of mucosal cooling on the perception of nasal airway obstruction.

The role of nasal congestion as a defence against respiratory viruses.

INTRODUCTION: This review discusses how nasal congestion may have benefits as a mechanism of defence against respiratory viruses. METHODS: A literature research was conducted on respiratory viruses and nasal congestion, following a recently published review on how temperature sensitivity is important for the success of common respiratory viruses. RESULTS: The literature reported that common respiratory viruses are temperature sensitive and replicate well at the cooler temperatures of the upper airways (32°C), but replication is restricted at body temperature (37°C). The amplitude of the phases of congestion and decongestion associated with the nasal cycle was increased on infection with respiratory viruses and this caused unilateral nasal congestion and obstruction. Nasal congestion and obstruction increase nasal mucosal temperature towards 37°C and therefore restricted the replication of respiratory viruses. CONCLUSION: Nasal congestion associated with the nasal cycle may act as a mechanism of respiratory defence against infection with respiratory viruses.

Effects of Hangeshashinto on the nasal physiological function: An in vitro study.

OBJECTIVE: Hangeshashinto is a Japanese Kampo medicine applied for the treatment of oral mucositis and gastroenteritis. Hangeshashinto exhibits broad-spectrum antibacterial activity and suppresses prostaglandin (PG)E2 production in the mucosa and has the ability to improve the inflammatory condition. In addition to these effects, because cAMP, a composition of Hangeshashinto, facilitates ciliary beat, Hangeshashinto could also improve the physiological function of the nasal mucosa, consist of ciliated epithelium, but details were unknown. METHODS: This study was aimed to investigate the effects of Hangeshashinto on the nasal mucosa. Healthy nasal mucosal sections were collected from the nasal septum of ten Japanese white rabbits, placed in a collagen dish for tissue culture, and rinsed with two different concentrations of Hangeshashinto solution (1.0%, n = 10 and 2.5%, n = 10) and cAMP solution (50µM, n=10 and 100 µM, n=10) or saline (control, n = 10). Ciliary beat frequency (CBF) as a physiological function of the nasal mucosa was recorded at 1, 3 and 7 days after rinsing, and histological evaluation of epithelial damage was performed at 7 days after rinsing. RESULTS: CBF in the 1.0% but not in the 2.5% Hangeshashinto group, increased at 3 and 7 days compared with that in the control group (p < 0.05). This trend was also observed in the CBF in the 100 µM cAMP group, significant difference was not observed between the CBF of the 1.0% Hangeshashinto group and the 100 µM cAMP group at 1, 3 and 7 days after rinsing (p > 0.05). Histological score only in the 2.5% Hangeshashinto group was lower than that in the control group (p < 0.05), while a significant decline was not observed in the other groups compared to that in the control group (p > 0.05). CONCLUSION: Our results suggest that 1.0% Hangeshashinto solution facilitates the physiological function of the nasal mucosa by promoting ciliary functions without histological damage of cilia epithelium. When applied with the appropriate concentration, Hangeshashinto could have ability to improve the physiological functions of the nasal mucosal epithelium.

Rapid activation of brainstem nuclei following TLR stimulation of the nasal mucosa.

We recently identified a novel neuroimmune mechanism in the nasal mucosa, in which activation of neuronal Toll­like receptor (TLR) 7 results in upregulation of epithelial TLRs, via release of substance P. In the present study, we assessed whether intranasal challenge with the TLR7 agonist R­837 additionally activated neurons in the central nervous system. Within one hour, R­837 induced activation of the nucleus of the solitary tract, as well as a small increase in nasal IL­6, but otherwise in the absence of an overt inflammatory response. It is tempting to speculate that it might be a direct interaction of R­837 with trigeminal neurons in order to alert the central nervous system of invading pathogens.

Functional analysis and evaluation of respiratory cilia in healthy Chinese children.

BACKGROUND: To aid in the diagnosis of Primary Ciliary Dyskinesia (PCD) and to evaluate the respiratory epithelium in respiratory disease, normal age-related reference ranges are needed for ciliary beat frequency (CBF), beat pattern and ultrastructure. Our aim was to establish reference ranges for healthy Chinese children. METHODS: Ciliated epithelial samples were obtained from 135 healthy Chinese children aged below 18 years by brushing the inferior nasal turbinate. CBF and beat pattern were analysed from high speed video recordings. Epithelial integrity and ciliary ultrastructure were assessed using transmission electronic microscopy. RESULTS: The mean CBF from 135 children studied was 10.1 Hz (95% CI 9.8 to 10.4). Approximately 20% (ranged 18.0-24.2%) of ciliated epithelial edges were found to have areas of dyskinetically beating cilia. Normal beat pattern was observed in ciliated epithelium from all subjects. We did not find any effect of exposure to second hand smoke on CBF in our subjects. Microtubular defects were found in 9.3% of all of the cilia counted in these children, while other ciliary ultrastructural defects were found in less than 3%. CONCLUSIONS: We established the reference range for CBF, beat pattern and ultrastructure in healthy Chinese children. Using similar methodology, we found a lower overall mean CBF than previously obtained European values. This study highlights the need to establish normative data for ciliary function in different populations.

In vivo and in vitro observation of nasal ciliary motion in a guinea pig model.

IMPACT STATEMENT: Cilia play an important role in the airway defense mechanism. So far, studies on ciliary function have mainly been based on in vitro methods. Images of in vivo ciliary motion are very difficult to capture. In this study, we describe a novel approach to observe and analyze nasal ciliary motion in living animals with comparison to in vitro observation. Such images of ciliary motion from living animals have not been reported to date. The result of the study indicates that in vivo ciliary physiological function differs from ex vivo and in vitro conditions in many ways, such as the stability over time and response to temperature variation. This is a good foundation for further in vivo analysis of airway ciliary physiological function in animals as well as humans.

Ciliary beat frequency of in vitro human nasal epithelium measured with the simple high-speed microscopy is applicable for safety studies of nasal drug formulations.

Nasal drug formulations can be effective for local delivery of therapeutic drugs to the sinonasal mucosa or for systemic drug delivery by absorption directly into the bloodstream. The growing field of potential nasal therapies includes nasal vaccination and even treatment of neurodegenerative diseases. However, it is important that nasal drug formulations don't have a disruptive effect on the cilia and mucosa of nasal epithelium. Mucociliary clearance represents the first host defence of the respiratory tract that requires the coordinated beating of cilia. A key parameter to determine mucociliary clearance is ciliary beat frequency (CBF). The objective of this study was to validate the high-speed digital imaging for CBF measurements in nasal MucilAir™ in vitro model and to test its potential for ciliotoxicity studies to evaluate the safety of investigational nasal drug formulations. Our CBF measuring setup was first validated by benzalkonium chloride, a common-practice preservative with cilio-inhibiting effect. Next, MucilAir™ model was treated with mometasone nasal spray (Mommox®/Mometasone Sandoz®). Short term cilio-stimulatory effect and dose dependent effect of mometasone nasal spray were demonstrated. Post-treatment analysis showed un-altered ultrastructure of MucilAir™ model. In conclusion, characterization of the ciliary activity of nasal MucilAir™ in vitro model and its response to relevant agents with herein developed efficient and reproducible set up for CBF analysis show great potential of this model for airway ciliotoxicity studies.

Non-Reflex Defense Mechanisms of Upper Airway Mucosa: Possible Clinical Application.

The sinonasal mucosa has an essential role in defense mechanisms of the upper respiratory tract. The innate immune system presents the primary defense against noxious microorganisms followed by induction of the adaptive immune mechanisms as a consequence of the presence of pathogens. This well-known activation of adaptive immune system in response to presence of the antigen on mucosal surfaces is now broadly applicated in vaccinology research. Prevention of infectious diseases belongs to substantial challenges in maintaining the population health. Non-invasive, easily applicable mucosal vaccination purposes various research opportunities that could be usable in daily practice. However, the existence of multiple limitations such as rapid clearance of vaccine from nasal mucosa by means of mucociliary transport represents a great challenge in development of safe and efficient vaccines. Here we give an updated view on nasal functions with focus on nasal mucosal immunity and its potential application in vaccination in nearly future.

Spaceflight-Associated Changes in the Opacification of the Paranasal Sinuses and Mastoid Air Cells in Astronauts.

Importance: Head congestion is one of the most common somatic symptoms experienced by astronauts during spaceflight; however, changes in the opacification of the paranasal sinuses or mastoid air cells in astronauts have not been adequately studied. Objectives: To quantify preflight to postflight changes in the opacification of the paranasal sinuses and mastoid air cells in Space Shuttle astronauts and International Space Station (ISS) astronauts and to assess whether there are differences between the 2 groups of astronauts. Design, Setting, and Participants: This cohort study examined preflight and postflight head magnetic resonance images (MRIs) of 35 astronauts who had participated in either a short-duration (≤30 days) Space Shuttle mission or a long-duration (>30 days) ISS mission and had undergone both preflight and postflight MRI. Images were obtained before and after spaceflight. Images were evaluated by 2 neuroradiologists blinded to which mission each astronaut had flown and to which images were preflight or postflight images. Exposure: Spaceflight on the Space Shuttle or the ISS. Main Outcomes and Measures: Measured outcomes included preflight to postflight changes in Lund-Mackay scores for the paranasal sinuses and in scores grading mastoid effusions. Results: Most astronauts in both the Space Shuttle group (n = 17; 15 men; mean [SD] age at launch, 47.7 [3.1] years) and the ISS group (n = 18; 14 men; mean [SD] age at launch, 48.6 [4.7] years) exhibited either no change or a reduction in paranasal sinus opacification as seen on postflight MRI scans (Space Shuttle group: 6 [35.3%] had no sinus opacification before or after spaceflight, 5 [29.4%] had less sinus opacification after spaceflight, 3 [17.6%] had the same amount of sinus opacification before and after spaceflight, and 3 [17.6%] had increased paranasal sinus opacification after spaceflight; ISS group: 8 [44.4%] had no sinus opacification before or after spaceflight, 4 [22.2%] had less sinus opacification after spaceflight, 1 (5.6%) had the same amount of sinus opacification before and after spaceflight, and 5 [27.8%] had scores consistent with increased paranasal sinus opacification after spaceflight). Long-duration spaceflight (ISS group) was associated with an increased risk of mastoid effusion relative to short-duration spaceflight (relative risk, 4.72; 95% CI, 1.2-18.5). Images were obtained a mean (SD) 287.5 (208.6) days (range, 18-627 days) prior to and 6.8 (5.8) days (range, 1-20 days) after spaceflight. Astronauts had undergone either a mean (SD) of 13.6 (1.6) days of spaceflight on the Space Shuttle (17 astronauts) or 164.8 (18.9) days on the ISS (18 astronauts). Conclusions and Relevance: This study found that exposure to spaceflight conditions on the ISS is associated with an increased likelihood for the formation of mastoid effusions. There was no association between exposure to spaceflight conditions and changes in paranasal sinus opacification. The limitations of this study include lack of information concerning medical history and mission-specific operational experience for individual astronauts. Further studies are indicated to determine the cause and composition of the mastoid effusions.

Effect of PM2.5 on MicroRNA Expression and Function in Nasal Mucosa of Rats With Allergic Rhinitis.

BACKGROUND: Particulate matter 2.5 (PM2.5) refers to particulate matter with aerodynamic equivalent diameter less than or equal to 2.5 µm, which is an important component of air pollution. PM2.5 aggravates allergic rhinitis (AR) and promotes AR nasal mucosa inflammation. Therefore, the influence of PM2.5 inhalation exposure on microRNA (miRNA) expression profiles and function in the nasal mucosa of AR rats was investigated. METHODS: Female Sprague Dawley rats were distributed randomly to 2 groups: AR model PM2.5 exposure group (ARE group) and AR model PM2.5-unexposed control group (ARC group). The rats of ARE group were made to inhale PM2.5 at a concentration of 200 µg/m3, 3 h/day, for 30 days. miRNA expression profiles of the nasal mucosa from both groups were determined using an miRNA gene chip and were verified by quantitative real-time PCR (qRT-PCR). Gene function enrichment analysis was performed using bioinformatics analysis. RESULTS: The ARE group revealed 20 significantly differentially expressed miRNAs, including 4 upregulated and 16 downregulated miRNAs (fold change > 1.5 or < 0.66, P < .05). Of these, 9 selected miRNAs were verified by qRT-PCR, and the results of 8 miRNAs were in accordance with the miRNA gene chip results, with highly positive correlation (r = .8583, P = .0031). Numerous target genes of differentially expressed miRNAs were functionally enriched in high-affinity immunoglobulin E receptor signaling, ErbB signaling, mucin O-glycans biosynthesis, transforming growth factor ß signaling, mitogen-activated protein kinase signal transduction, phosphatidylinositol signaling, mucopolysaccharide biosynthesis, mammalian target of rapamycin signaling, T cell receptor signaling, Wnt signaling, chemokine signal transduction, and natural killer cell-mediated cytotoxicity pathways. CONCLUSIONS: PM2.5 causes significant changes in miRNA expression in the nasal mucosa of AR rats. miRNA plays an important role in regulating PM2.5 effects in AR rat biological behavior and mucosal inflammation. This study provides a theoretical basis for the prevention and treatment of AR from the effects of environmental pollution on the gene regulation mechanism.

Measurement of mucociliary clearance in the patients with multiple sclerosis.

OBJECTIVES: The aim of the present study was to measure nasal mucociliary clearance (NMC) time in the patients with MS and to compare the findings with healthy population. METHODS: Totally 97 individuals including 47 patients with relapsing-remitting multiple sclerosis and 50 healthy volunteers were enrolled into the study. Saccharin clearance test was performed on both groups and NMC time was measured. Data analysis was performed by SPSS version 24.0 statistics program (SPSS Inc., Chicago, Illinois, USA). Statistical tests were interpreted at p < 0.05 significance level. RESULTS: The NMC time averages in MS patients and healthy control group were 12.43 ± 4.05 min and 8.14 ± 2.87 min, respectively; the difference between the groups was significant (p < 0.001). There was a statistically strong association between NMC time values and Expanded Disability Status Scale (EDSS) values in MS patients (r = 0.817, p < 0.001). CONCLUSION: We found nasal mucociliary transport time longer in MS patients than healthy population in the present study. To the best of our knowledge, there is not any study conducted about this topic in the literature. We believe that our findings would shed a light on further studies.

Mucociliary clearance in patients with continuous ambulatory peritoneal dialysis / Aclaramiento mucociliar en pacientes con diálisis peritoneal ambulatoria continua

INTRODUCTION: Mucociliary clearance (MC) is a critical defense mechanism for the protection of the entire respiratory system. Nasal colonization of some pathogens and chronical nasal infections are important risk factors for peritonitis. Any disturbance in the MC causes stasis of secretions and secondary infections. OBJECTIVE: The aim of the study was to evaluate the patients with chronic kidney disease (CKD) receiving continuous ambulatory peritoneal dialysis (CAPD) in terms of nasal MC. More specifically, the goal is to investigate the possible correlation between the nasal MC and peritonitis. METHODS: Forty CAPD patients and 39 healthy volunteers were involved in the study. The nasal MC was evaluated with the saccharin test, in which a 1 mm diameter saccharin particle was carefully placed on the antero-medial surface of inferior nasal concha. The time taken by the subjects from the placement of particle to the perception of the sweet taste was taken as mucociliary clearance time (MCT). The groups were compared in terms of MCT. The patient group was evaluated in terms of a peritonitis history, and the correlations with MC were analyzed. RESULTS: Patient group with CKD consisted of 16 females and 24 males with a mean age of 32.4 years; healthy individuals in the control group consisted of 17 women and 22 men with a mean age of 33.3 years. There was not a significant difference in terms of mean MC time in patients with CKD when compared with the individuals in the control group. The comparison between the mean MCT in the patients who had a history of peritonitis and patients without peritonitis was statistically significant (p < 0.05). CONCLUSIONS: Unique for being conducted with patients in continuous ambulatory peritoneal dialysis, the current study shows that although the MC of CKD patients and healthy individuals is similar, patients with low rates of MC appear to present an increased incidence of peritoneal infection. Considering the small sample investigated, an invitation to future confirmatory studies would be appropriate

INTRODUCCIÓN: El aclaramiento mucociliar (AM) es un mecanismo de defensa fundamental para la protección del sistema respiratorio. La colonización nasal de algunos patógenos y las infecciones nasales crónicas son factores de riesgo importantes de peritonitis. Cualquier alteración en el AM provoca estasis de secreciones e infecciones secundarias. OBJETIVO: El objetivo de este estudio fue evaluar el AM nasal de los pacientes con nefropatía crónica (NC) que recibían diálisis peritoneal ambulatoria continua (DPAC). Más concretamente, el objetivo fue estudiar la posible relación entre el AM nasal y la peritonitis. MÉTODOS: Cuarenta pacientes en DPAC y 39 voluntarios sanos participaron en el estudio. El AM nasal se evaluó con la prueba de sacarina, en la que se colocó cuidadosamente una partícula de sacarina, de 1 mm de diámetro, en la superficie anteromedial del cornete nasal inferior. El tiempo transcurrido desde el momento en que se colocó la partícula hasta que los pacientes percibieron el sabor dulce se consideró el tiempo de aclaramiento mucociliar (TAM), parámetro que se empleó para hacer la comparación entre los grupos. Se evaluaron los antecedentes de peritonitis en el grupo de pacientes y se analizaron las correlaciones con el AM. RESULTADOS: El grupo de pacientes con NC constó de 16 mujeres y 24 hombres con una media de edad de 32,4 años. Los pacientes sanos en el grupo control fueron 17 mujeres y 22 hombres con una media de edad de 33,3 años. No se observó una diferencia significativa en el tiempo medio de AM en pacientes con NC respecto a los pacientes del grupo control. La comparación entre el TAM medio en los pacientes con antecedentes de peritonitis y en pacientes sin peritonitis fue estadísticamente significativa (p < 0,05). CONCLUSIONES: Único por llevarse a cabo en pacientes con diálisis peritoneal ambulatoria continua, el estudio actual muestra que, aunque el AM de pacientes con NC y pacientes sanos es similar, los pacientes con tasas bajas de AM parecen presentar un aumento de la incidencia de infección peritoneal. Teniendo en cuenta la pequeña muestra estudiada, consideramos conveniente realizar nuevos estudios de confirmación

Experimental Acute Exposure to Thirdhand Smoke and Changes in the Human Nasal Epithelial Transcriptome: A Randomized Clinical Trial.

Importance: No previous studies have shown that acute inhalation of thirdhand smoke (THS) activates stress and survival pathways in the human nasal epithelium. Objective: To evaluate gene expression in the nasal epithelium of nonsmoking women following acute inhalation of clean air and THS. Design, Setting, and Participants: Nasal epithelium samples were obtained from participants in a randomized clinical trial (2011-2015) on the health effects of inhaled THS. In a crossover design, participants were exposed, head only, to THS and to conditioned, filtered air in a laboratory setting. The order of exposures was randomized and exposures were separated by at least 21 days. Ribonucleic acid was obtained from a subset of 4 healthy, nonsmoking women. Exposures: By chance, women in the subset were randomized to receive clean air exposure first and THS exposure second. Exposures lasted 3 hours. Main Outcomes and Measures: Differentially expressed genes were identified using RNA sequencing with a false-discovery rate less than 0.1. Results: Participants were 4 healthy, nonsmoking women aged 27 to 49 years (mean [SD] age, 42 [10.2] years) with no chronic diseases. A total of 389 differentially expressed genes were identified in nasal epithelium exposed to THS, while only 2 genes, which were not studied further, were affected by clean air. Enriched gene ontology terms associated with stress-induced mitochondrial hyperfusion were identified, such as respiratory electron transport chain (q = 2.84 × 10-3) and mitochondrial inner membrane (q = 7.21 × 10-6). Reactome pathway analysis identified terms associated with upregulation of DNA repair mechanisms, such as nucleotide excision repair (q = 1.05 × 10-2). Enrichment analyses using ingenuity pathway analysis identified canonical pathways related to stress-induced mitochondrial hyperfusion (eg, increased oxidative phosphorylation) (P = .001), oxidative stress (eg, glutathione depletion phase II reactions) (P = .04), and cell survival (z score = 5.026). Conclusions and Relevance: This study found that acute inhalation of THS caused cell stress that led to the activation of survival pathways. Some responses were consistent with stress-induced mitochondrial hyperfusion and similar to those demonstrated previously in vitro. These data may be valuable to physicians treating patients exposed to THS and may aid in formulating regulations for the remediation of THS-contaminated environments.

Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors.

Introduction: Kolliphor® EL (K-EL) is among the most useful surfactants in the preparation of emulsions. However, it is associated with low hydrophobic drug loading in the resulting emulsified formulation. Methods: In this study, a formulation for intranasal administration of butylidenephthalide (Bdph), a candidate drug against glioblastoma (GBM), was prepared. Physical characteristics of the formulation such as particle size, zeta potential, conductivity, and viscosity were assessed, as well as its cytotoxicity and permeability, in order to optimize the formulation and improve its drug loading capacity. Results: The optimized formulation involved the integration of polyethylene glycol 400 (PEG 400) in K-EL to encapsulate Bdph dissolved in dimethyl sulfoxide (DMSO), and it exhibited higher drug loading capacity and drug solubility in water than the old formulation, which did not contain PEG 400. Incorporation of PEG 400 as a co-surfactant increased Bdph loading capacity to up to 50% (v/v), even in formulations using Kolliphor® HS 15 (K-HS15) as a surfactant, which is less compatible with Bdph than K-EL. The optimized Bdph formulation presented 5- and 2.5-fold higher permeability and cytotoxicity, respectively, in human GBM than stock Bdph. This could be attributed to the high drug loading capacity and the high polarity index due to DMSO, which increases the compatibility between the drug and the cell. Rats bearing a brain glioma treated with 160 mg/kg intranasal emulsified Bdph had a mean survival of 37 days, which is the same survival time achieved by treatment with 320 mg/kg stock Bdph. This implies that the optimized emulsified formulation required only half the Bdph dose to achieve an efficacy similar to that of stock Bdph in the treatment of animals with malignant brain tumor.