1.Efficacy and safety assessment of transnasal nebulisation of budesonide in children with adenoid hypertrophy.
Wenxin CHEN ; Zhiying ZHOU ; Jiahua SHEN ; Zhiyi WANG ; Yong FU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2024;38(12):1154-1160
Objective:To investigate the efficacy and assess the safety of transnasal nebulisation of budesonide in children with adenoid hypertrophy. Methods:Children with adenoid hypertrophy who attended the Children's Hospital of Zhejiang University School of Medicine between December 2021 and December 2022 were randomly assigned to budesonide high-dose group(Group A: budesonide 1 mg/dose + saline nasal rinse), budesonide low-dose group(Group B: budesonide 0.5 mg/dose + saline nasal rinse), and control group(Group C: saline nasal rinse), and each group 20 children were collected separately, The efficacy and safety of transnasal nebulisation of budesonide in children with adenoid hypertrophy were assessed by comparing the symptomatic VAS scores, adenoidal nasopharyngeal lateral radiographs A/N values, nocturnal sleep oximetry(SaO2), and the incidence of adverse events during the treatment period of 8-week in the three groups. Results:The 8-week baseline differences in adenoid A/N values were statistically different between groups A and B(P<0.001) and A and C(P=0.022), with the reduced amount in adenoid volume being most pronounced in group A, which differed from the other two groups. With the increase of intervention time, SaO2 levels gradually increased(F=154.725, P<0.001) and VAS scores gradually decreased(F=165.616, P<0.001) in all three groups. After 8 weeks of treatment, there was no statistically significant difference in SaO2 level(P=0.085) between groups A and B. There was a statistically significant difference in VAS total scores between Group A and Group B (P < 0.05) . The improvement of SaO2and total VAS score in group A was higher than that in group B. There was a statistically significant difference in the comparison of SaO2 level and total VAS score between groups A and B, and between groups A and C(P<0.01); after the intervention of the three groups, showing the greatest improvement of total VAS score and SaO2in the group A, followed by Group B. There was no statistically significant difference in the incidence of adverse events among Groups A, B, and C throughout the trial. Conclusion:The treatment of children with adenoid hypertrophy by intranasal nebulisation of budesonide suspension has good efficacy and safety, which is conducive to reducing the size of adenoids, improving the clinical symptoms of children with adenoid hypertrophy, and improving the SaO2of nocturnal sleep, and it has a certain clinical application value.
Humans
;
Budesonide/administration & dosage*
;
Adenoids
;
Child
;
Male
;
Female
;
Hypertrophy
;
Nebulizers and Vaporizers
;
Treatment Outcome
;
Administration, Intranasal
;
Child, Preschool
2.Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation.
Min YAN ; Lan ZHANG ; Lu-Lu ZHANG ; Zhen-Qiang ZHANG ; Hua-Hui ZENG ; Xiang-Xiang WU
China Journal of Chinese Materia Medica 2023;48(9):2426-2434
Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.
Mice
;
Animals
;
Tripterygium
;
Liposomes
;
Glycosides/therapeutic use*
;
Administration, Intranasal
;
Lipopolysaccharides
;
Central Nervous System
;
Cognitive Dysfunction/drug therapy*
;
Inflammation/metabolism*
;
Tumor Necrosis Factor-alpha/metabolism*
;
Cardiac Glycosides
3.Factors affecting nasal drug delivery and design strategies for intranasal drug delivery.
Xiaoyun HU ; Xiao YUE ; Chuanbin WU ; Xuejuan ZHANG
Journal of Zhejiang University. Medical sciences 2023;52(3):328-337
Intranasal drug delivery system is a non-invasive drug delivery route with the advantages of no first-pass effect, rapid effect and brain targeting. It is a feasible alternative to drug delivery via injection, and a potential drug delivery route for the central nervous system. However, the nasal physiological environment is complex, and the nasal delivery system requires "integration of medicine and device". Its delivery efficiency is affected by many factors such as the features and formulations of drug, delivery devices and nasal cavity physiology. Some strategies have been designed to improve the solubility, stability, membrane permeability and nasal retention time of drugs. These include the use of prodrugs, adding enzyme inhibitors and absorption enhancers to preparations, and new drug carriers, which can eventually improve the efficiency of intranasal drug delivery. This article reviews recent publications and describes the above mentioned aspects and design strategies for nasal intranasal drug delivery systems to provide insights for the development of intranasal drug delivery systems.
Administration, Intranasal
;
Drug Delivery Systems
;
Pharmaceutical Preparations
;
Drug Carriers
;
Brain
;
Nasal Cavity/physiology*
;
Nasal Mucosa
4.A multi-center observation of the therapeutic efficacy of Bencycloquidium bromide in the treatment of seasonal allergic rhinitis with predominant symptoms of rhinorrhea.
Weini HU ; Tianhong ZHANG ; Yinghong ZHANG ; Chao MENG ; Lifeng XIE ; Yu SONG ; Chen DU ; Chiyu XU ; Yali DU ; Qiang ZUO ; Fengyang AN ; Yuhui WANG ; Cuida MENG ; Lei ZHANG ; Dongdong ZHU ; Li ZHU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(7):550-555
Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale(VAS) of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from (8.89±3.31) on day 0 to (3.71±2.51) on day 14(P<0.001), VAS score of nasal symptoms decreased from (24.86±7.40) on day 0 to (6.84±5.94) on day 14(P<0.001), VAS score of rhinorrhoea decreased from (6.88±2.06) on day 0 to (1.91±1.81) on day 14(P<0.001). Rhinoconjunctivitis quality of life questionnaire(RQLQ) score decreased from (94.63±33.35) on day 0 to (44.95±32.28) on day 14(P<0.001). The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.
Male
;
Female
;
Humans
;
Adult
;
Rhinitis, Allergic, Seasonal/drug therapy*
;
Nasal Sprays
;
Quality of Life
;
Administration, Intranasal
;
Rhinorrhea
;
Double-Blind Method
;
Treatment Outcome
;
Rhinitis, Allergic/drug therapy*
5.Mouse-adapted SARS-CoV-2 replicates efficiently in the upper and lower respiratory tract of BALB/c and C57BL/6J mice.
Jinliang WANG ; Lei SHUAI ; Chong WANG ; Renqiang LIU ; Xijun HE ; Xianfeng ZHANG ; Ziruo SUN ; Dan SHAN ; Jinying GE ; Xijun WANG ; Ronghong HUA ; Gongxun ZHONG ; Zhiyuan WEN ; Zhigao BU
Protein & Cell 2020;11(10):776-782
Adaptation, Physiological
;
Adenosine Monophosphate
;
administration & dosage
;
analogs & derivatives
;
pharmacology
;
therapeutic use
;
Administration, Intranasal
;
Alanine
;
administration & dosage
;
analogs & derivatives
;
pharmacology
;
therapeutic use
;
Animals
;
Betacoronavirus
;
genetics
;
physiology
;
Chlorocebus aethiops
;
Coronavirus Infections
;
drug therapy
;
virology
;
Disease Models, Animal
;
Female
;
Host Specificity
;
genetics
;
Lung
;
pathology
;
virology
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Mutation, Missense
;
Nasal Mucosa
;
virology
;
Pandemics
;
Pneumonia, Viral
;
drug therapy
;
virology
;
RNA, Viral
;
administration & dosage
;
genetics
;
Turbinates
;
virology
;
Vero Cells
;
Viral Load
;
Virus Replication
6.Comparison of ED of intranasal dexmedetomidine sedation in children with acyanotic congenital heart disease before and after cardiac surgery.
Jing ZHANG ; Qing YU ; Yang LIU ; Hui LIU ; Mang SUN ; Qin TIAN ; Shengfen TU
Journal of Southern Medical University 2020;40(6):864-868
OBJECTIVE:
To compare the median effective dose (ED) of intranasal dexmedetomidine for procedural sedation in uncooperative pediatric patients with acyanotic congenital heart disease before and after cardiac surgery.
METHODS:
We prospectively recruited 47 children (22 in preoperative group and 25 in postoperative group) who needed sedation for transthoracic echocardiography (TTE). A modified up-and-down sequential study design was employed to determine dexmedetomidine dose for each patient with a starting dose of 2 μg/kg in both groups; dexmedetomidine doses for subsequent subjects were determined according to the responses from the previous subject using the up-and-down method at a 0.25 μg/kg interval. The ED was determined using probit regression. The onset time, examination time, wake-up time and adverse effects were measured, and the safety was evaluated in terms of changes in vital signs every 5 min.
RESULTS:
The ED value of intranasal dexmedetomidine for sedation was 1.84 μg/kg (95% : 1.68-2.00 μg/kg) in children with congenital heart disease before cardiac surgery, and 3.38 μg/kg (95% : 3.21-3.54 μg/kg) after the surgery. No significant difference was found between the two groups in the demographic variables, onset time, examination time, wake-up time, or adverse effects.
CONCLUSIONS
In children with acyanotic congenital heart disease, the ED of intranasal dexmedetomidine for TTE sedation increases to 3.38 μg/ kg after cardiac surgery from the preoperative value of 1.84 μg/kg.
Administration, Intranasal
;
Cardiac Surgical Procedures
;
Child
;
Dexmedetomidine
;
Heart Defects, Congenital
;
surgery
;
Humans
;
Hypnotics and Sedatives
7.Research progress on traditional Chinese medicine in preventing and treating cerebral ischemia injury based on "nose-brain" pathway.
Zhen-Zhen WEI ; Xiao-Yan FANG ; Shuai-Ke FAN ; Meng-Fan PENG ; Ming BAI ; Ming-San MIAO
China Journal of Chinese Materia Medica 2019;44(22):4800-4805
Due to the increasing incidence of central nervous system diseases,especially the increasing incidence and mortality of stroke,brain-targeted drug delivery has attached more and more attention. Nasal administration,as one of the ways of brain-targeted administration,can effectively make the drug delivered to the brain in a targeted way after by passing the blood-brain barrier,providing a new idea for the treatment of central nervous system diseases. Therefore,it is a promising administration way. In recent years,the treatment of encephalopathy by nasal administration of traditional Chinese medicine has become a hot topic in the research of traditional Chinese medicine. Ischemic stroke is one of the most important diseases endangering human health. Nasal administration has a history of thousands of years in treatment of stroke. Modern medical research has proved that there is a subtle connection between the nasal cavity and the brain,and the complex and ingenious structure of the nasal cavity provides the possibility for drugs delivery to the brain through the nose. Drug administration through nasal cavity has obvious advantages in treatment of central nervous system diseases represented by ischemic stroke. Nasal administration is characterized by non-invasion,low infection,rapid absorption and brain targeting. The author will expound the theoretical basis of brain targeting of nasal administration from the aspects of anatomy and physiology,and summarize the transport pathway of drugs through the nose into the brain,the in vitro and in vivo experimental research basis of the " nose-brain"pathway,and the clinical nasal administration of traditional Chinese medicine to prevent cerebral ischemia. It provides a reference for better research of drugs to prevent and treat cerebral ischemia injury through the " nose-brain"pathway and lays a foundation for further research of the " nose-brain" pathway.
Administration, Intranasal
;
Brain
;
Brain Ischemia/drug therapy*
;
Drug Delivery Systems
;
Humans
;
Medicine, Chinese Traditional
;
Nasal Mucosa
;
Pharmaceutical Preparations
8.Intranasal Administration of Oxytocin Attenuates Stress Responses Following Chronic Complicated Stress in Rats
Yu YANG ; Haijie YU ; Reji BABYGIRIJA ; Bei SHI ; Weinan SUN ; Xiaojiao ZHENG ; Jun ZHENG
Journal of Neurogastroenterology and Motility 2019;25(4):611-622
BACKGROUND/AIMS: Gastrointestinal (GI) symptoms may develop when we fail to adapt to various stressors of our daily life. Central oxytocin (OXT) can counteract the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular) of OXT significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on GI dysmotility in rats. However, intracerebroventricular administration is an invasive pathway. Intranasal administration can rapidly deliver peptides to the brain avoiding stress response. The effects of intranasal OXT on hypothalamus-pituitary-adrenal axis and GI motility in CCS conditions have not been investigated. METHODS: A CCS rat model was set up, OXT 5, 10, or 20 μg were intranasal administered, 30 minutes prior to stress loading. Central CRF and OXT expression levels were analyzed, serum corticosterone and OXT concentrations were measured, and gastric and colonic motor functions were evaluated by gastric emptying, fecal pellet output, and motility recording system. RESULTS: Rats in CCS condition showed significantly increased CRF expression and corticosterone concentration, which resulted in delayed gastric emptying and increased fecal pellet output, attenuated gastric motility and enhanced colonic motility were also recorded. OXT 10 μg or 20 μg significantly reduced CRF mRNA expression and the corticosterone concentration, OXT 20 μg also helped to restore GI motor dysfunction induced by CCS. CONCLUSION: Intranasal administration of OXT has an anxiolytic effect and attenuates the hypothalamus-pituitary-adrenal axis in response to CCS, and gave effects which helped to restore GI dysmotility, and might be a new approach for the treatment of stress-induced GI motility disorders.
Administration, Intranasal
;
Animals
;
Anti-Anxiety Agents
;
Brain
;
Colon
;
Corticosterone
;
Corticotropin-Releasing Hormone
;
Gastric Emptying
;
Gastrointestinal Motility
;
Models, Animal
;
Oxytocin
;
Peptides
;
Rats
;
RNA, Messenger
9.Anxiolytic Action of Taurine via Intranasal Administration in Mice
Biomolecules & Therapeutics 2019;27(5):450-456
Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine’s effect on anxiety. For the characterization of potential mechanism of taurine’s anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine’s anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.
Administration, Intranasal
;
Animals
;
Anxiety
;
Arm
;
Brain
;
Central Nervous System
;
Isoniazid
;
Mice
;
Picrotoxin
;
Receptors, Glycine
;
Seizures
;
Strychnine
;
Taurine
;
Yohimbine
10.Intranasal Treatment With 1, 25-Dihydroxyvitamin D3 Alleviates Allergic Rhinitis Symptoms in a Mouse Model
Sung Woo CHO ; Yu Lian ZHANG ; Young Kyung KO ; Jae Min SHIN ; Jun Ho LEE ; Chae Seo RHEE ; Dong Young KIM
Allergy, Asthma & Immunology Research 2019;11(2):267-279
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.
Administration, Intranasal
;
Animals
;
Anti-Allergic Agents
;
Calcitriol
;
Cell Proliferation
;
Dendritic Cells
;
Eosinophils
;
Flow Cytometry
;
Immunoglobulin E
;
Immunoglobulin G
;
Immunoglobulins
;
Inflammation
;
Interleukin-10
;
Interleukin-13
;
Interleukin-4
;
Interleukin-5
;
Lymph Nodes
;
Lymphocytes
;
Major Histocompatibility Complex
;
Mice
;
Models, Animal
;
Ovalbumin
;
Ovum
;
Rhinitis, Allergic
;
RNA, Messenger
;
Vitamin D

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