Intranasal Spray Research Articles

Differed spontaneous dissociative symptoms following the use of esketamine intranasal spray in a patient suffering from treatment-resistant depression: a case report.

Intranasal esketamine is used in France for treatment-resistant depression. Dissociative symptoms are common side effects during treatment sessions. We report a case of delayed spontaneous dissociative symptoms following esketamine administration. A 20-year-old female with treatment-resistant depression received esketamine treatment. Dissociative symptoms occurred during sessions and persisted at a distance, often accompanied by anxiety. Delayed dissociative phenomena disappeared within the fourth week of treatment by esketamine. The literature mainly discusses dissociation during esketamine treatment sessions, with limited data on differed spontaneous episodes. Three hypotheses are discussed concerning the mechanism of occurrence of these dissociative phenomena, including esketamine's direct effect, central nervous system sensitization, and anxiety-induced dissociation. We present the first case of differed spontaneous dissociative effects after intranasal esketamine administration for treatment-resistant depression. Our main hypothesis suggests that esketamine may act as a 'pattern' for dissociative experiences, heightening the patient's ability to discern these phenomena during other instances of dissociation, such as acute anxiety attacks. Further research is needed to validate this hypothesis.

Effect of nasal carriage of Bacillus species on COVID-19 severity: a cross-sectional study.

Intranasal sprays containing Bacillus species are being researched for treating viral respiratory tract infections. The aim of this study was to assess the relationship between the nasal carriage of Bacillus and COVID-19 severity. This was a cross-sectional study that collected nasopharyngeal samples from adults 18 years and above visiting two COVID-19 testing centers in Lagos, Nigeria, between September 2020 and September 2021. Bacillus species were cultured from the samples and confirmed using 16 s rRNA gene sequencing. The dependent variable was COVID-19 status classified as negative, asymptomatic, mild, or severe. The independent variable was the nasal carriage of Bacillus species. Multinomial regression analysis was done to determine the association between nasal carriage of Bacillus and COVID-19 severity after adjusting for age, sex, and co-morbidity status. A total of 388 participants were included in the study with mean (standard deviation) age of 40.05 (13.563) years. Sixty-one percent of the participants were male, 100 (25.8%) had severe COVID-19, 130 (33.5%) had pre-existing comorbidity, and 76 (19.6%) had Bacillus cultured from their nasopharyngeal specimen. Bacillus species presence was significantly associated with higher odds of severe COVID-19 compared to having a negative COVID-19 status (AOR = 3.347, 95% CI: 1.359, 8.243). However, the presence of Bacillus species was significantly associated with lower odds of severe COVID-19 compared to having a mild COVID-19 status. The study suggests that nasal carriage of Bacillus species is associated with the clinical course of COVID-19 and supports the exploration of Bacillus species in the management of viral respiratory tract infections.IMPORTANCEWith the introduction of intranasal spray containing Bacillus species for the treatment of viral respiratory tract infections, such as COVID-19 and respiratory syncytial virus, identifying the association between the nasal carriage of Bacillus species and COVID-19 susceptibility and severity will help further substantiate the investigation of these bacteria for COVID-19 prevention and treatment. This study evaluated the association between the carriage of Bacillus species in the nasopharyngeal tract and COVID-19 severity and found that the presence of Bacillus species in the nasopharynx may significantly impact the clinical course of COVID-19.

A single intranasal dose of essential oil spray confers modulation of the nasopharyngeal microbiota and short-term inhibition of Mannheimia in feedlot cattle: a pilot study

Five essential oils (EOs) were previously characterized in vitro and identified as candidate EOs for the development of an intranasal EO spray to mitigate bovine respiratory disease (BRD) pathogens. In the present study, these EOs were evaluated for their potential to (i) reduce BRD pathogens, (ii) modulate nasopharyngeal microbiota, and (iii) influence animal performance, feeding behavior and immune response when a single dose administered intranasally to feedlot cattle. Forty beef steer calves (7–8 months old, Initial body weight = 284 ± 5 kg [SE]) received either an intranasal EO spray (ajowan, thyme, fennel, cinnamon leaf, and citronella) or PBS (Control; n = 20/group) on day 0. Deep nasopharyngeal swabs were collected on days (d) -1, 1, 2, 7, 14, 28, and 42 and processed for 16S rRNA gene sequencing, qPCR, and culturing. Significant effects of EO on community structure (d1), microbial richness and diversity, relative abundance of some dominant phyla (d1, d2, and d14), and the overall interaction network structure of the nasopharyngeal microbiota were detected. The relative abundance of Mannheimia was lower in the EO calves (4.34%) than in Control calves (10.4%) on d2, and M. haemolytica prevalence on d7 as compared to control calves. Feed intake, average daily gain, feeding behavior, and blood cell counts were not affected by EO treatment. Overall, a single intranasal dose of EO spray resulted in moderate modulation of nasopharyngeal microbiota and short-term inhibition of Mannheimia while not influencing animal performance, feeding behavior or immune response. Our study, for the first time, shows the potential use of intranasal EO to mitigate BRD in feedlot cattle.

Assessing Nasal Epithelial Dynamics: Impact of the Natural Nasal Cycle on Intranasal Spray Deposition.

This study investigated the intricate dynamics of intranasal spray deposition within nasal models, considering variations in head orientation and stages of the nasal cycle. Employing controlled delivery conditions, we compared the deposition patterns of saline nasal sprays in models representing congestion (N1), normal (N0), and decongestion (P1, P2) during one nasal cycle. The results highlighted the impact of the nasal cycle on spray distribution, with congestion leading to confined deposition and decongestion allowing for broader dispersion of spray droplets and increased sedimentation towards the posterior turbinate. In particular, the progressive nasal dilation from N1 to P2 decreased the spray deposition in the middle turbinate. The head angle, in conjunction with the nasal cycle, significantly influenced the nasal spray deposition distribution, affecting targeted drug delivery within the nasal cavity. Despite controlled parameters, a notable variance in deposition was observed, emphasizing the complex interplay of gravity, flow shear, nasal cycle, and nasal morphology. The magnitude of variance increased as the head tilt angle increased backward from upright to 22.5° to 45° due to increasing gravity and liquid film destabilization, especially under decongestion conditions (P1, P2). This study's findings underscore the importance of considering both natural physiological variations and head orientation in optimizing intranasal drug delivery.

Sphenopalatine Ganglion Block Using Intranasal Lignocaine Spray for Trigeminal Neuralgia: A Case Series

Abstract Various interventions have been tried for the management of trigeminal neuralgia which is a sharp, shooting recurrent neuropathic pain. The use of the sphenopalatine ganglion (SPG) block has been established as a fast, safe, and effective means of pain relief for these patients. Recently, 10% lignocaine spray has been described as a less invasive alternative for this block. We report seven patients of idiopathic trigeminal neuralgia with acute unilateral severe pain managed by SPG blocks using 10% intranasal lignocaine spray. Seven patients with unilateral trigeminal neuralgia were included in the study. Two puffs of 10% lignocaine were sprayed into the nostril of the affected side in a slightly medial and inferior direction. Before the procedure and 30 min later, Visual Analog Scale (VAS) scoring was done. The procedure was repeated in case of no pain relief after 1 h of nasal spray (VAS 4 or 5). All patients were observed for 2 h and oral medication was prescribed if required after assessment at 24 h. Four patients reported complete relief (VAS 0 or 1) and two of them reported pain (VAS 4 and 5) after 24 h. The procedure had to be repeated in two patients with no pain relief (VAS 4 and 5) after 1 h. There was no relief in one patient even after repeated administration (VAS 5). The findings suggest a role for intranasal lignocaine spray for SPG block in trigeminal neuralgia for alleviating acute exacerbations of pain and obtaining quick relief.

The impact of oxytocin on emotion recognition and trust: Does disordered eating moderate these relationships?

The current study aimed to investigate the impact of oxytocin on emotion recognition, trust, body image, affect, and anxiety and whether eating disorder (ED) symptoms moderated any of these relationships. Participants (n = 149) were female university students, who were randomly allocated to receive in a double-blind nature, a single dose of oxytocin intranasal spray (n = 76) or a placebo (saline) intranasal spray (n = 73). Participants were asked to complete an experimental measure of emotion recognition and an investor task aimed to assess trust. The oxytocin group exhibited better overall performance on the emotion recognition task (especially with recognising positive emotions), and a decline in state positive affect than the control group at post-intervention. However, these effects were not moderated by ED symptom severity, nor were effects found for state anxiety, negative affect, body image and recognising negative emotions in the emotion recognition task. The current findings contribute to the growing literature on oxytocin, emotion recognition and positive affect and suggest that ED pathology does not moderate these relationships. Future research would benefit from examining the efficacy of an oxytocin intervention using a within-subjects, cross-over design, in those with sub-clinical and clinical EDs, as well as healthy controls.

Effects of nasal desmopressin spray versus topical epinephrine on surgical field clarity and hemodynamics in endonasal dacryocystorhinostomy: a randomized clinical study

Background A bloodless surgical field coupled with stable hemodynamics is pivotal for successful surgical intervention, especially in endonasal surgeries. This study investigates the effect of intranasal desmopressin spray in reducing surgical bleeding and on hemodynamics compared with topical epinephrine in patients scheduled for endonasal dacryocystorhinostomy (DCR). Methods Fifty-two patients were randomly allocated into two groups in this double-blind clinical study: Desmopressin group (n=26): patients received two puffs of desmopressin acetate 10 μg/puff in the side of the nasal cavity ipsilateral to the obstructed lacrimal duct (20 µg totally) 60 min before the surgery. Epinephrine group (n=26): patients received topical 1 : 100 000 epinephrine in the nasal cavity ipsilateral to the obstructed lacrimal duct via 3 soaked packs placed in the middle meatus for 5 min after induction of general anesthesia and before the start of surgery. Results The median clarity of the surgical field based on the BOEZAART grading system was significantly clearer in the desmopressin group compared with epinephrine group. The duration of surgery was significantly shorter in the desmopressin group (66.92±5.04 min) compared with epinephrine group (71.73±5.45 min). Mean arterial blood pressure (MABP) and heart rate (HR) were statistically significant higher in epinephrine group compared to the desmopressin group at 2 and 5 min after topical epinephrine compared with desmopressin group. Conclusion Pre-emptive 20 ug single dose of intranasal desmopressin provides a clear surgical field with no hemodynamics effects compared with topical epinephrine in patients undergoing endonasal dacryocystorhinostomy. Clinicaltrial.gov (ref: NCT05507476, date of registration: 18-8–2022).

Intranasal alpha-adrenergic receptor agonists and corticosteroids as medical treatments for nasal congestion

Nasal congestion has been a longstanding issue which exerts burdens on both individual patients and society as a whole. It arises from various underlying illnesses like nasal polyposis, rhinosinusitis, allergic rhinitis and rhinitis medicamentosa, but the fundamental mechanism of induced nasal congestion is nasal mucosas swelling as a result of inflammation in all of these cases. Among all the therapies currently available, intranasal sprays of alpha-adrenergic receptor agonists or corticosteroids appeared to be prominent options. After reviewing research on treatments extensively, limited studies focused on the comparison of -adrenergic agonists and corticosteroids. This research explores the mechanisms, efficacy, and safety of these two medical approaches. Intranasal alpha-adrenergic receptor agonist sprays target the smooth muscles for vasoconstriction, acting rapidly to give way to airflow. They are effective as a treatment for short-term nasal congestion, otherwise, continued use may lead to rhinitis medicamentosa. Corticosteroid sprays, on the other hand, aim to reduce the severity of nasal inflammation via suppression of pro-inflammatory molecules. They are a promising treatment barely with concerns about the occurrence of side effects, authenticated by their excellent pharmaceutical performance over years.

Short-term effectiveness of single-dose intranasal spray COVID-19 vaccine against symptomatic SARS-CoV-2 Omicron infection in healthcare workers: a prospective cohort study

The pivotal phase 3 efficacy clinical trial has demonstrated that a two-dose regimen of dNS1-RBD (Beijing Wantai Biological Pharmacy Enterprise,Beijing, China) is well-tolerated and provides wide protection against SARS-CoV-2 infection. However, the effectiveness of a single-dose regimen is still unknown. We aimed to estimate the effectiveness of one-dose of dNS1-RBD against symptomatic Omicron infections in real-world conditions. This prospective cohort study was conducted during an Omicron outbreak among healthcare workers in Xiamen, China, from December 22, 2022 to January 16, 2023. Participants chose to receive single-dose of dNS1-RBD or remain unvaccinated based on personal preference. Healthcare workers daily validated their SARS-CoV-2 infection status, using either RT-PCR or rapid antigen test. A survey questionnaire was conducted to gather information on acute symptoms from individuals infected with SARS-CoV-2. The primary outcome was the symptomatic SARS-CoV-2 infections after enrollment in the dNS1-RBD recipients or the control group among all participants and by prior COVID-19 vaccination status. On December 22, 2022, a total of 1391 eligible participants without a history of prior SARS-CoV-2 infection were enrolled. Among them, 550 received single-dose of dNS1-RBD, while 841 remained unvaccinated. In the total cohort, the range of follow-up time was 1∼26 days. During the study period, a total of 880 symptomatic SARS-CoV-2 infections were identified in the total cohort. The adjusted vaccine effectiveness against symptomatic SARS-CoV-2 infections and the infections requiring medical attention were 19.0% (95% CI: 6.7, 29.7, P=0.004) and 59.4% (95% CI: 25.1, 78.0, P=0.004) in the total cohort, 11.6% (95% CI:-2.4, 23.7, P=0.100) and 55.3% (95% CI: 15.3, 76.4, P=0.014) in the participants with inactivated COVID-19 vaccination history, as well as 87.0% (95% CI: 72.6, 93.9, P < 0.001) and 84.2% (95% CI:-41.8, 98.2, P=0.099) in the naïve participants, respectively. When administered as a booster to individuals with a history of inactivated COVID-19 vaccination, a single-dose of dNS1-RBD provides protection against infections requiring medical attention at least in the short-term after vaccination. The data also showed that a single-dose of dNS1-RBD is protective against symptomatic SARS-CoV-2 infections as a primary immunization for individuals without prior exposure, but due to the limited sample size of naïve participants, further research with a larger sample size is needed to make a solid conclusion. Xiamen Science and Technology Bureau 2022 General Science and Technology Plan Project and the Bill & Melinda Gates Foundation.

Effect of intra‐nasal insulin therapy on food intake among African American adults: the FIINAAL study

AbstractBackgroundIntranasal insulin is a promising treatment for cognitive decline in Alzheimer’s Disease (AD) and mild cognitive impairment (MCI). However, intranasal insulin has been shown to promote weight loss, leading to concerns about decreased appetite, decreased food intake, and unintentional weight loss as negative side effects among metabolic and ingestive behavior effects of intranasal insulin sprays among AD and MCI patients. But, side effects related to food intake and appetite are not well studied, particularly among African American adults who are under‐represented in AD research.Method39 middle‐aged, cognitively normal, community‐dwelling African American adults (Table 1) were enrolled in the Food Intake and Intranasal Insulin in African American Adults (FIINAAL) study assessing effects of intranasal insulin on acute food intake and appetite ratings. This double‐blind, placebo‐controlled, randomized crossover study compared a single intranasal dose of 10 IUs of Novologã insulin, delivered with the Kurveã device, to an intranasal placebo. Participants ate a eucaloric, macronutrient‐balanced lead‐in diet for three days prior to each dose. The dose was administered in the morning following an overnight fast. An ad libitum test lunch followed the dose and participants rated their appetite immediately before and after each dose, and after the meal. Mixed effects linear model t‐tests were used to compare differences in food intake and appetite ratings between insulin and placebo conditions.ResultThere were no significant differences in test lunch energy (calories) or macronutrient intake between insulin and placebo conditions. However, fullness ratings increased significantly more after receiving a dose of insulin than after a dose of placebo (Figure 1). In addition, desire to consume sweet and fatty foods decreased significantly more after insulin than after placebo (Figure 2).ConclusionIn middle aged African American adults, acute intranasal insulin administration was associated with a reduced desire to eat palatable foods and with increased feelings of fullness, but not with reduced food intake at a test meal. Because reduced appetite appears to be an acute side effect of intranasal insulin administration, future work should study whether chronic intranasal insulin administration results in reduced appetite and, consequently, reduced food intake and body weight over time.

Overcoming the clinical challenges of traditional ayahuasca: a first-in-human trial exploring novel routes of administration of N,N-Dimethyltryptamine and harmine

Recently, the Amazonian plant medicine “ayahuasca”—containing the psychedelic compound N,N-dimethyltryptamine (DMT) and numerous β-carboline alkaloids, such as harmine—has been suggested to exhibit beneficial effects in patients with affective and other mental health disorders. Although ayahuasca ingestion is considered safe, its pharmacokinetics/pharmacodynamics and tolerability profile pose some challenges and may limit the clinical applicability in vulnerable patient populations. While overdosing and the admixture of intolerable plant constituents may explain some of the common adverse reactions, the peroral route of administration may represent another relevant source of gastro-intestinal intolerabilities and unpredictable pharmacokinetics across users. To overcome these challenges, the present work aimed at creating ayahuasca-analogue formulations with improved pharmacokinetics and tolerability profiles. To this end, we developed peroral formulas and compared them with parenteral formulas specifically designed to circumvent the gastro-intestinal tract. In more detail, peroral administration of a capsule (containing purified DMT and harmine) was tested against a combined administration of an oromucosal harmine tablet and an intranasal DMT spray at two dose levels in an open-label within-subject study in 10 healthy male subjects. Pharmacokinetic and pharmacodynamic profiles were assessed by means of continuous blood sampling, vital sign monitoring, and psychometric assessments. Common side effects induced by traditional herbal ayahuasca such as nausea, vomiting, and diarrhea were significantly attenuated by our DMT/harmine formulations. While all preparations were well tolerated, the combined buccal/intranasal administration of harmine and DMT yielded substantially improved pharmacokinetic profiles, indicated by significantly reduced variations in systemic exposure. In conclusion, the combined buccal/intranasal administration of harmine and DMT is an innovative approach that may pave the way towards a safe, rapid-acting, and patient-oriented administration of DMT/harmine for the treatment of affective disorders.Clinical Trial Registration:clinicaltrials.gov, identifier NCT04716335

Allergic rhinitis: a comprehensive view of the problem

Currently, allergic sensitization is considered as one of the key causes of the development of chronic inflammatory processes in the nasal cavity and paranasal sinuses. The choice of optimal drugs for the treatment of allergic rhinitis still remains a relevant, socially significant and interdisciplinary problem. The article analyzes the modern strategy for the treatment of allergic rhinitis and assesses the incidence of comorbid pathology associated with allergic sensitization in patients with this pathology. In accordance with the latest clinical guidelines, a discussion of a stepwise approach to the treatment of allergic rhinitis was carried out. Based on data from a number of studies, the advantages of prescribing intranasal corticosteroids (InGCS) and leukotriene receptor antagonists (ALR) in the treatment of allergic rhinitis, including when combined with bronchial asthma and chronic rhinosinusitis with nasal polyps, have been identified. Among the officially registered drugs for the basic treatment of allergic rhinitis, the characteristics of the original intranasal spray mometasone furoate and the leukotriene receptor blocker montelukast are described in detail. The discussion describes the possibilities of potentiating the effects of topical corticosteroids through combination with leukotriene receptor antagonists. A clinical example demonstrates the feasibility of using a combination of the intranasal corticosteroid Nasonex with the leukotriene receptor blocker Singulair to control the course of allergic rhinitis and chronic rhinosinusitis with nasal polyps and, as a consequence, prevent the development of remodeling of the respiratory tract mucosa in such patients. During a follow-up examination after 3 months of therapy, the patient noted a subjective improvement in general well-being, nasal breathing, sense of smell, normalization of sleep, and a significant decrease in nasal discharge. There is no need for decongestants, sneezing is not a concern, and there is no respiratory discomfort. The combined use of ALR and InGCS enhances the anti-inflammatory effect of therapy.

Intranasal dexmedetomidine improves postoperative sleep quality in older patients with chronic insomnia: a randomized double-blind controlled trial.

Objective: This study was determined to investigate the impact of intranasal dexmedetomidine (DEX) on postoperative sleep quality in older patients (age over 65) with chronic insomnia during their hospitalization after surgery. Design: A randomized double-blind controlled trial was conducted to compare the effects of intranasal dexmedetomidine spray with a placebo group. Setting and Participants: The study was carried out at Xiangya Hospital, Central South University. 110 participants with chronic insomnia were analyzed. Methods: This trial enrolled older patients who underwent total hip/knee arthroplasty and randomized them to receive intranasal dexmedetomidine (2.0μg/kg) or saline daily at around 9 p.m. after surgery until discharge. The primary outcomes were subjective sleep quality assessed with the Leeds Sleep Evaluation Questionnaire (LSEQ). The secondary outcomes included the objective sleep quality measured with the Acti-graph, the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI). The other outcomes included the incidence of delirium, levels of inflammatory factors, visual analog scale (VAS) pain scores, postoperative opioid consumption, and treatment-related adverse events. Results: 174 patients were screened for eligibility, and 110 were recruited and analyzed. The DEX group had significantly higher scores on both the LSEQ-Getting to sleep and LSEQ-Quality of Sleep at each time point compared to the placebo (p < 0.0001), The least squares (LS) mean difference in LSEQ-GTS score at T0 between placebo group and DEX group was 2 (95% CI, -1-6), p = 0.4071 and at T5 was -14 (95% CI, -17 to -10), p < 0.0001; The LS mean difference in the LSEQ-QOS score at T0 was -1 (95% CI, -4 to 1), p = 0.4821 and at T5 was -16 (95% CI, -21 to -10), p < 0.0001. The DEX group exhibited significant improvement in Total Sleep Time (TST), Sleep Onset Latency (SOL), and Sleep Efficiency (SE), at each time point after treatment compared to the placebo group (p < 0.0001). The PSQI and ISI scores in the DEX group were reduced after treatment (p < 0.001). No significant adverse events were reported with the use of dexmedetomidine. Conclusion and Implications: This study demonstrates that intranasal administration of dexmedetomidine improves postoperative sleep quality in older patients with chronic insomnia who undergo surgery, without increasing the incidence of adverse effects. Clinical Trial Registration: http://www.chictr.org.cn/, identifier ChiCTR2200057133.

The impact of anaphylaxis on the absorption of intranasal epinephrine in anaesthetized non-naive beagle dogs.

Epinephrine delivery via an intranasal spray (neffy) is being evaluated as an additional option to treat severe allergic reaction and may provide clinical benefit by reducing the time to dosing in community settings by avoiding needles. Given that hypotension is a hallmark symptom of severe allergic reactions, a preclinical study was conducted to evaluate the impact of this factor on epinephrine absorption via neffy. The objective of this study was to evaluate the absorption of epinephrine via neffy in a dog model of anaphylaxis with severe hypotension. Epinephrine absorption via neffy was evaluated in anesthetized beagle dogs under both normal conditions and hypotension associated with anaphylaxis. Atotal of 14 dogs (10 males and 4 females) were dosed with neffy, 1.0 mg, under normal conditions, followed by neffy, 1.0 mg, under conditions of anaphylaxis. The mean maximum concentration of epinephrine was higher during anaphylaxis than under normal conditions (2,670± 2,150 pg/mL and 1,330± 739 pg/mL [P< .05]). Relative to normal conditions, anaphylaxis resulted in higher overall epinephrine exposure (area under the curve from 0 to 45 minutes= 54,400± 18,100 min×pg/mL and 34,300± 21,500 minutes×pg/mL [P< .05]), which is likely due to the increase in vascular permeability commonly observed during severe allergic reactions. Taken together with real-world evidence from nasal naloxone treatment for opioid overdose demonstrating that the reduced blood flow or hypotension associated with overdose does not appear to suppress naloxone's efficacy, the current findings demonstrate that epinephrine is well absorbed following neffy delivery during the hypotension associated with severe anaphylaxis reactions.

51 Evaluation of the Effects of a Single Intranasal Dose of Essential oil Spray on the Nasopharyngeal Microbiota of Feedlot Cattle: A Pilot Study

Abstract Five essential oils (EO) were previously characterized in vitro and identified as candidates for the development of an intranasal EO spray to inhibit the colonization and proliferation of bovine respiratory disease (BRD) pathogens, especially at feedlot entry when cattle are most susceptible to BRD. In the present pilot study, these EO were evaluated for their potential to reduce BRD pathogens and to modulate nasopharyngeal microbiota in feedlot cattle. Angus-crossbred calves [n = 40; 7to 8 months old; initial BW = 284 ± 5 kg (SE)] received either an intranasal EO spray consisting of ajowan, thyme, fennel, cinnamon leaf, and citronella (0.025%, vol/vol per EO) suspended in PBS (3 mL per nostril) or PBS (Control) on day (d) 0. Deep nasopharyngeal swabs were collected on d -1 (24 h before EO administration), 1, 2, 7, 14, 28, and 42, and processed for microbiota characterization using 16S rRNA gene. The calves that received EO had similar feed intake (P = 0.62) and average daily gain (P = 0.37) than control calves. Overall bacterial concentration estimated by qPCR was greater in control (P =0.049) than EO group, with EO group having reduced bacterial concentration on d 2 (P = 0.01) and d 7 (P=0.07). Sequencing results revealed that overall community structure of nasopharyngeal microbiota was different between EO and control calves (PERMANOVA: R2 = 0.01, P = 0.02), and was strongly affected by time (R2 = 0.1, P = 0.001). Within individual sampling day, the effect of EO on community structure was only detected on d 1 (R2 = 0.05, P = 0.03). Microbial richness (observed ASVs) and diversity (Shannon and Inverse Simpson) were not different between the two groups (P ≥ 0.17). The effect of EO on the most dominant phyla was observed (P ≤ 0.05) with Proteobacteria (d14), Firmicutes (d1, 14), Actinobacteriota (d14), and Bacteroidota (d2, 14). Among the predominant genera: Moraxella, Ralstonia, Mycoplasma, Mannheimia, Filobacterium, Pseudomonas, Pasteurella, and Corynebacterium, the abundance of Mannheimia (4.34% vs. 10.4%) and Filobacterium (2.53% vs. 11.9%) were reduced (P &amp;lt; 0.05) by EO on d 2. In control calves, Mannheimia was enriched by 3.9-fold (P &amp;lt; 0.05) from d -1 (2.66%) to d 2 (10.4%), whereas it remained constant in EO calves (P &amp;gt; 0.05) between these days (2.23% and 4.34%). Corynebacterium was also decreased (P &amp;lt; 0.05) in EO calves on d 1 (1.06% vs. 2.58%). The BRD-associated Histophilus genus was low (mean 0.02%), so EO effect was not assessed. Overall, a single dose of intranasal EO spray modulated nasopharyngeal microbiota and reduced the abundance of Mannheimia within 48 h post administration while having no effect on feed intake and daily gain. Our study highlights that nasally dosing EO may modulate respiratory microbiota and potentially mitigate bovine respiratory disease in finishing cattle.

Real-world effectiveness of an intranasal spray A8G6 antibody cocktail in the post-exposure prophylaxis of COVID-19

Previously, we identified an antibody combination A8G6 that showed promising efficacy in COVID-19 animal models and favorable safety profile in preclinical models as well as in a first-in-human trial. To evaluate the real-word efficacy of A8G6 neutralizing antibody nasal spray in post-exposure prophylaxis of COVID-19, an open-label, non-randomized, two-arm, blank-controlled, investigator-initiated trial was conducted in Chongqing, China (the register number: ChiCTR2200066416). High-risk healthy participants (18–65 years) within 72 h after close contact to COVID-19 patients were recruited and received a three-dose (1.4 mg/dose) A8G6 treatment daily or no treatment (blank control) for 7 consecutive days. SARS-CoV-2 infection occurred in 151/340 (44.4%) subjects in the blank control group and 12/173 (6.9%) subjects in the A8G6 treatment group. The prevention efficacy of the A8G6 treatment within 72 h exposure was calculated to be 84.4% (95% CI: 74.4–90.4%). Moreover, compared to the blank-control group, the time from the SARS-CoV-2 negative to the positive COVID-19 conversion was significantly longer in the AG86 treatment group (mean time: 3.4 days vs 2.6 days, p = 0.019). In the secondary end-point analysis, the A8G6 nasal treatment had no effects on the viral load at baseline SARS-CoV-2 RT-PCR positivity and the time of the negative COVID-19 conversion. Finally, except for 5 participants (3.1%) with general adverse effects, we did not observe any severe adverse effects related to the A8G6 treatment. In this study, the intranasal spray AG86 antibody cocktail showed potent efficacy for prevention of SARS-CoV-2 infection in close contacts of COVID-19 patients.

Fast Acting, Dry Powder, Needle-Free, Intranasal Epinephrine Spray: A Promising Future Treatment for Anaphylaxis.

Epinephrine intramuscular (IM) autoinjector is a life-saving drug for the emergency treatment of immediate-type allergic reactions (type I). Nevertheless, it is sometimes applied incorrectly or underused because of short shelf life, high costs, fear of use, or inconvenience of carrying. FMXIN002, a nasal powder spray of epinephrine, was developed as a needle-free alternative. To compare epinephrine pharmacokinetics, pharmacodynamics, and safety after the administration of the FMXIN002 nasal spray versus autoinjector. An open-label trial was performed in 12 adults with seasonal allergic rhinitis without asthma. Epinephrine pharmacokinetics, pharmacodynamics, and safety were compared between FMXIN002 (1.6 mg and 3.2 mg) administered intranasally with/without a nasal allergen challenge and IM (0.3 mg) EpiPen. FMXIN002 3.2 mg, administered after a nasal allergen challenge, displayed a shorter Tmax than EpiPen (median: 2.5 minutes vs 9.0 minutes, statistically nonsignificant [NS]) and a significantly shorter time when the measured analyte concentration is 100 pg/mL during the absorption phase pg/mL (median: 1.0 minutes vs 3.0 minutes for FMXIN002, P < .02). Moreover, FMXIN002 3.2 mg administered after the challenge test has resulted in a doubling of the maximal measured plasma analyte concentration over the sampling period (1110 vs 551 pg/mL, NS); area under the curve from 0 to 8 hours was 56% higher (672 vs 431 hours pg/mL, compared with EpiPen, NS). Pharmacodynamic response was comparable at all treatments. FMXIN002 was well tolerated, and treatment-emergent adverse events (AEs) were mild, local, and resolved spontaneously. No AEs were reported after the administration of EpiPen in our study. FMXIN002 was stable for 2 years at room temperature conditions. However, variability in the pharmacokinetics (expressed incoefficient of variation) is high. Having a prior nasal allergen challenge results in a substantial increase and speed of absorption. Intranasal absorption of dry powder epinephrine is faster than EpiPen offering a clinical advantage in the short therapeutic window for the treatment of anaphylaxis. The FMXIN002 product offers a needle-free, pocket-size, safe, user-friendly, and stable alternative to epinephrine autoinjectors.

Role of Desmopressin Acetate before Percutaneous Ultrasound-Guided Kidney Biopsy in Patients with Kidney Dysfunction.

The most common complication of percutaneous kidney biopsy is bleeding, which can be seen in up to one-third of cases. The aim of this study was to evaluate the effect of prebiopsy administration of intranasal desmopressin acetate in reducing the incidence of biopsy-related bleeding complications. This was a prospective randomized double-blind pilot study conducted at our center from January 2021 to September 2022. Consecutive adult patients who underwent native percutaneous kidney biopsy with an estimated glomerular filtration rate (eGFR) ≤45 ml/min/1.73 m2 were randomized into a placebo (saline intranasal spray) group versus intranasal desmopressin group. The bleeding complications were compared between the two groups. A total of 80 patients who underwent kidney biopsy at our center from January 2021 to September 2022 with eGFR ≤45 ml/min/1.73 m2 were included (40 patients in desmopressin group and 40 patients in non-desmopressin group) in the study. The mean age of the patients was 44 ± 12 years with a mean eGFR of 20.82 ± 12.64 ml/min/1.73 m2. Intranasal desmopressin administration before kidney biopsy was associated with a significantly higher number of minor bleeding complications (P = 0.02) and no significant reduction in major complications (P = 0.15) when compared with a group that did not receive desmopressin. Other complications like hypotension, flushing, and vasovagal syncope were not statistically significantly associated with the use of desmopressin. Our study did not find any utility of prophylactic desmopressin use before kidney biopsy in patients with kidney dysfunction.

Aerosol Inhalation of Chimpanzee Adenovirus Vectors (ChAd68) Expressing Ancestral or Omicron BA.1 Stabilized Pre-Fusion Spike Glycoproteins Protects Non-Human Primates against SARS-CoV-2 Infection.

Current COVID-19 vaccines are effective countermeasures to control the SARS-CoV-2 virus pandemic by inducing systemic immune responses through intramuscular injection. However, respiratory mucosal immunization will be needed to elicit local sterilizing immunity to prevent virus replication in the nasopharynx, shedding, and transmission. In this study, we first compared the immunoprotective ability of a chimpanzee replication-deficient adenovirus-vectored COVID-19 vaccine expressing a stabilized pre-fusion spike glycoprotein from the ancestral SARS-CoV-2 strain Wuhan-Hu-1 (BV-AdCoV-1) administered through either aerosol inhalation, intranasal spray, or intramuscular injection in cynomolgus monkeys and rhesus macaques. Compared with intranasal administration, aerosol inhalation of BV-AdCoV-1 elicited stronger humoral and mucosal immunity that conferred excellent protection against SARS-CoV-2 infection in rhesus macaques. Importantly, aerosol inhalation induced immunity comparable to that obtained by intramuscular injection, although at a significantly lower dose. Furthermore, to address the problem of immune escape variants, we evaluated the merits of heterologous boosting with an adenovirus-based Omicron BA.1 vaccine (C68-COA04). Boosting rhesus macaques vaccinated with two doses of BV-AdCoV-1 with either the homologous or the heterologous C68-COA04 vector resulted in cross-neutralizing immunity against WT, Delta, and Omicron subvariants, including BA.4/5 stronger than that obtained by administering a bivalent BV-AdCoV-1/C68-COA04 vaccine. These results demonstrate that the administration of BV-AdCoV-1 or C68-COA04 via aerosol inhalation is a promising approach to prevent SARS-CoV-2 infection and transmission and curtail the pandemic spread.

Olfactory drug delivery with intranasal sprays after nasal midvault reconstruction

Conductive olfaction and nose to brain drug delivery are important processes that remain limited by inadequate odorant or drug delivery to the olfactory airspace. Primary challenges include anatomic barriers and poor targeting to the olfactory region. This study uses computational fluid dynamics to investigate the effects of nasal midvault surgery on olfactory drug delivery with intranasal sprays. Soft tissue elevation, spreader flaps, and spreader grafts were performed on two fresh cadaveric specimens, using computed tomography for airway reconstruction. Nasal airflow and drug particle transport simulations were performed under these conditions: inhalation rate (15, 30 L/min), spray velocity (1, 5, 10 m/s), spray location (top, bottom, center, medial, lateral), head position (upright, supine, forward, backward), and particle size (1–100 µm). Simulation results were used to calculate drug particle deposition to the olfactory airspaces and bulbs. Total olfactory deposition was < 5% but attained a maximum of 36.33% when sorted by particle size. There was no association between nasal midvault surgery and olfactory deposition. No single parameter or technique demonstrated superior olfactory deposition, but smaller particle size, slower spray velocity, and higher inhalation rate tended to optimize olfactory deposition, providing important implications for future intranasal spray and drug design to target the olfactory airspace.