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Results for “Administration, Intranasal”

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PubMed1991

[Sedation with intranasal midazolam for endoscopy of the upper digestive tract].

Twenty-nine patients, ranked ASA 1 or 2, scheduled for diagnostic gastroduodenal fibroscopy were randomly allocated into three treatment groups: intranasal midazolam (IN) 0.15 mg.kg-1; intramuscular midazolam (IM) 0.15 mg.kg-1, and placebo (P). Sedation and the fibroscopy were all carried out by the same anaesthetist and fibroscopist. Efficiency and tolerance of the method were assessed by monitoring the heart rate, systolic and diastolic arterial blood pressure, arterial oxygen saturation (pulse oximetry), the degrees of sedation, anxiety, and anterograde as well as retrograde amnesia. The patient's and endoscopist's reactions were also considered. Patients in group P were older than those of the other two groups (p less than 0.01). Sedation was more important and patients less anxious in groups IN and IM than in group P. Three patients in group IM had retrograde amnesia. There were no significant differences between the degrees of anterograde amnesia in the three groups. At no time during the study were there any significant differences in SpO2 between and within groups. Four out of the 9 patients in group P had a bad opinion of their experience, as compared with two out of the 20 in the midazolam groups; the difference was not statistically significant. Three hours after the procedure, all patients were fully awake. Intranasal administration of midazolam therefore seemed to be an interesting alternative for gastroduodenal fibroscopy, because it was simple, non traumatic, well tolerated, and did not result in arterial desaturation.

Administration, Intranasal↗

PubMed2000

Nasal toxicological investigations of Carbopol 971P formulation of apomorphine: effects on ciliary beat frequency of human nasal primary cell culture and in vivo on rabbit nasal mucosa.

OBJECTIVE: The objective of this study was to investigate the nasal toxicity of a mucoadhesive Carbopol 971P formulation of apomorphine. MATERIALS AND METHODS: The effects of different concentrations of Carbopol 971P and apomorphine on ciliary beat frequency (CBF) were studied in suspension cultures of human nasal epithelial cells. The rabbit nasal mucosal tolerance of the formulation and its components were investigated using light microscopy. Different groups of the rabbits received twice daily, air puffs, glucose, glucose/apomorphine, Carbopol 971P or Carbopol 971P/apomorphine for 1 week (glucose-treated rabbits) or 1, 2 and 4 weeks (other treatments). RESULTS: Both Carbopol 971P and apomorphine showed both concentration- and time-dependent inhibitory effects on the CBF. The effects on CBF were: apomorphine, 1.0% w/v, irreversible ciliostasis; 0.1 and 0.5% w/v, reversible cilio-inhibition; 0.01%w/v, irreversible cilio-stimulation; and Carbopol 971P, 0.1 and 0.25% w/v, partially-reversible cilio-inhibition. Glucose and glucose/apomorphine physical mixture caused mild inflammation. Carbopol 971P (both with and without apomorphine) caused severe inflammation, which increased with duration of treatment. Necrosis, squamous metaplasia or ciliary degeneration was not observed. CONCLUSIONS: Due to the severe inflammation caused by Carbopol 971P with and without apomorphine, we conclude that this polymer is not a suitable carrier for intranasal administration of apomorphine. This is in spite of the reversible effects of Carbopol 971P (0.1 and 0. 25% w/v) and apomorphine (0.1 and 0.5% w/v) on CBF.

Acrylates↗

PubMed1999

Effects of the common cold and intranasal fluticasone propionate treatment on mucosal host defense assessed by human saliva.

OBJECTIVE: The purpose of this investigation was to study the effect of a potent topical steroid, fluticasone propionate, on patients with early signs and symptoms of the common cold. To characterize the mucosal inflammatory response, salivary defense factors and flow rate in these patients were analyzed. STUDY DESIGN: Forty patients with symptoms of the common cold were randomized into 2 groups to receive either high-dose fluticasone propionate (100 microg per nostril) or placebo 4 times daily for 6 days. Paraffin-stimulated whole saliva was collected on day 1 (before the onset of medication), day 7 (posttreatment), and day 21 (follow-up). RESULTS: Salivary flow rate, innate host defense factors, and total protein content were not affected by the common cold. IgA increased between day 7 and day 21 (P < or = .01; Student 2-tailed t test), and the relative proportions of salivary peroxidase and IgA increased on day 7 (P = .01) and day 21 (P= .05). In patients receiving fluticasone, saliva flow rate was lower on day 21 (P < or = .05) than on days 1 and 7. The innate salivary defense factors were not affected, but IgA increased both on day 7 (P < or = .001) and on day 21 (P < or = .001) in comparison with day 1. CONCLUSIONS: Of the oral mucosal defense factors, only IgA is activated during the common cold. Intranasally administrated fluticasone propionate does not have a suppressive effect on salivary antimicrobial capacity.

Administration, Intranasal↗

PubMed2006

Intranasal ketorolac challenge for the diagnosis of aspirin-exacerbated respiratory disease.

BACKGROUND: Intranasal administration of aspirin-lysine has been used in Europe for the diagnosis of aspirin-exacerbated respiratory disease. It has a low adverse effect profile and is believed to be safer for asthmatic patients, particularly those with a low baseline forced expiratory volume in 1 second, in whom oral aspirin challenge would be contraindicated. Ketorolac, a nonsteroidal anti-inflammatory drug useful for severe pain, is available in the United States in parenteral form. OBJECTIVE: To determine whether ketorolac nasal challenge has acceptable specificity and sensitivity for diagnosing aspirin-exacerbated respiratory disease. METHODS: Twenty-nine patients with suspected aspirin-exacerbated respiratory disease were challenged with nasal ketorolac before oral challenge and desensitization with aspirin. Symptoms, objective changes in nasal examination findings, and peak nasal inspiratory flow values were recorded. Nasal lavage fluid for cysteinyl leukotriene analysis was collected. Ketorolac doses of 2.1, 5.2, or 7.8 mg were administered and compared with the results of oral aspirin challenge. RESULTS: Eighteen patients had a positive challenge reaction to oral aspirin. Ketorolac nasal inhalation had a sensitivity of 78% and a specificity of 64%. Patients in the reactor group had significantly higher levels of cysteinyl leukotrienes after ketorolac challenge than in the nonreactor group. Mild bronchospasm occurred in 3 patients, and 2 of these occurred at higher starting doses of ketorolac. CONCLUSIONS: Nasal ketorolac administration is a reasonably accurate and safe method for diagnosing aspirin-exacerbated respiratory disease.

Administration, Intranasal↗

PubMed1990

Bile salt-fatty acid mixed micelles as nasal absorption promoters of peptides. II. In vivo nasal absorption of insulin in rats and effects of mixed micelles on the morphological integrity of the nasal mucosa.

The effectiveness of mixed micelles in promoting nasal absorption of peptides has been demonstrated in vivo by employing insulin as a model compound. Insulin in the absence of adjuvants was not absorbed following intranasal administration. The results confirmed previous findings by others that absorption of insulin via alternative routes required absorption enhancers. Mixed micelles between NaGC and linoleic acid were found to rapidly deliver insulin into systemic circulation, with a concomitant decrease in plasma glucose. The extent of the hypoglycemic response was significantly greater than that produced by NaGC alone (55 vs 47%, P less than 0.05). Emulsion of linoleic acid, on the other hand, did not produce any significant insulin absorption. The findings thus supported previous in situ data that mixed micelles were more effective than NaGC or linoleic acid in promoting nasal absorption of peptides. Histopathologic examination of the rat nasal mucosa revealed that the extent of morphological alterations caused by mixed micelles was of mild to moderate severity even after 5 hr of exposure. However, studies involving more frequent and prolonged exposures are necessary to assess the practicality of these adjuvants before any clinical application can be attempted.

Absorption↗

PubMed1994

The bioavailability of intranasal salmon calcitonin in healthy volunteers with and without a permeation enhancer.

Serum levels of radioimmunoactive salmon calcitonin (sCT) were determined in 10 healthy volunteers after intranasal administration (IN) of 100-, 205-, and 450-IU of sCT with 0.5% sodium tauro-24,25-dihydrofusidate (STDHF), a 200-IU commercial IN formulation, and a 100-IU intramuscular (IM) formulation. Relative to the IM dose, the bioavailabilities of the IN formulations containing 0.5% STDHF were 3.9, 7.9, and 7.4%, respectively. The 200-IU commercial formulation resulted in serum levels above the limit of detection in only 5 of 10 patients, with an average bioavailability of 1.6%.

Adjuvants, Pharmaceutic↗

PubMed2002

Insoluble powder formulation as an effective nasal drug delivery system.

PURPOSE: To evaluate the utility of insoluble powder formulation for nasal systemic drug delivery. METHODS: To compare the efficacy of liquid and powder formulations, the nasal absorption of drugs was examined in rats using hydrophilic compounds with various molecular weights (MW) such as phenol red, cyanocobalamin, and fluorescein isothiocyanate (FITC)-Dextrans, and several kinds of powder. Intranasal residence time was also compared among the different formulations. RESULTS: All the drugs examined were absorbed through the nasal mucosa to varying extent; their systemic bioavailability decreased with increasing MW. Insoluble calcium carbonate (CaCO3) powder formulation provided increased absorption of drugs over the wide range of MW from 354 to 77,000 Da. In the case of phenol red, intranasal administration as a CaCO3 powder formulation resulted in a plasma concentration profile similar to that of an intravenous bolus dose due to its very rapid and complete absorption from the nasal cavity. Furthermore, improved bioavailability of FITC-Dextran (MW 4,400; FD-4) was also achieved with other insoluble powders as well as CaCO3, but not with soluble powders such as lactose, d-sorbitol, and d-mannitol. Insoluble powder formulation prolonged the residence time of FD-4 within the nasal cavity. CONCLUSIONS: Insoluble powder formulations improve nasal bioavailability predominantly by retarding drug elimination from the absorption site and appear to be effective for nasal systemic drug delivery.

Administration, Intranasal↗

PubMed2000

A comparison of the clinical efficacy and safety of intranasal fluticasone propionate and antihistamines in the treatment of rhinitis.

Adequate management of allergic rhinitis is needed to avoid its considerable adverse social, clinical, and economic impact. Both topical intranasal steroids and oral or topical antihistamines are recognised as effective treatments for this condition. In comparative studies, however, intranasal steroids and, in particular, fluticasone propionate aqueous nasal spray (FPANS), have afforded consistently better symptomatic relief, and have a greater beneficial effect on quality of life. Furthermore, the addition of an antihistamine to FPANS therapy has generally produced little further benefit. Intranasal administration is associated with a low systemic absorption of fluticasone propionate and, following regular use of FPANS, placebo, or an oral antihistamine, no significant differences were seen between treatment groups in plasma or urinary cortisol. Overall, therefore, the data indicate that FPANS is superior to second-generation antihistamines in the management of allergic rhinitis.

Administration, Intranasal↗

PubMed1999

A universal influenza A vaccine based on the extracellular domain of the M2 protein.

The antigenic variation of influenza virus represents a major health problem. However, the extracellular domain of the minor, virus-coded M2 protein is nearly invariant in all influenza A strains. We genetically fused this M2 domain to the hepatitis B virus core (HBc) protein to create fusion gene coding for M2HBc; this gene was efficiently expressed in Escherichia coli. Intraperitoneal or intranasal administration of purified M2HBc particles to mice provided 90-100% protection against a lethal virus challenge. The protection was mediated by antibodies, as it was transferable by serum. The enhanced immunogenicity of the M2 extracellular domain exposed on HBc particles allows broad-spectrum, long-lasting protection against influenza A infections.

Administration, Intranasal↗

PubMed2005

Oxytocin increases trust in humans.

Trust pervades human societies. Trust is indispensable in friendship, love, families and organizations, and plays a key role in economic exchange and politics. In the absence of trust among trading partners, market transactions break down. In the absence of trust in a country's institutions and leaders, political legitimacy breaks down. Much recent evidence indicates that trust contributes to economic, political and social success. Little is known, however, about the biological basis of trust among humans. Here we show that intranasal administration of oxytocin, a neuropeptide that plays a key role in social attachment and affiliation in non-human mammals, causes a substantial increase in trust among humans, thereby greatly increasing the benefits from social interactions. We also show that the effect of oxytocin on trust is not due to a general increase in the readiness to bear risks. On the contrary, oxytocin specifically affects an individual's willingness to accept social risks arising through interpersonal interactions. These results concur with animal research suggesting an essential role for oxytocin as a biological basis of prosocial approach behaviour.

Administration, Intranasal↗

PubMed2004

Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction.

PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following intranasal administration in healthy male subjects and in Viagra-responsive erectile dysfunction (ED) patients. Erectile response was assessed by RigiScan trade mark in healthy subjects without visual sexual stimulation (VSS) and in Viagra-responsive ED patients with VSS. In healthy subjects, mean C(max) and AUC((0-t)) increased in a dose-dependent manner. Median T(max) was 0.50 h and mean t(1/2) ranged from 1.85 to 2.09 h. In both studies, an erectile response induced by PT-141 administration was statistically significant, compared to placebo, at doses greater than 7 mg, with the onset of the first erection occurring in approximately 30 min. PT-141 was safely administered and well tolerated in both studies. A maximum-tolerated dose was not identified. Flushing and nausea were the most common adverse events reported in both studies and no clinically significant changes in vital signs, laboratory tests, ECGs, or physical exams were observed. Based upon its erectogenic potential and tolerability profile, PT-141 is a promising candidate for further evaluation as a treatment for male ED.

Administration, Intranasal↗

PubMed2002

Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus.

C57BL/6 mice were sensitized to Aspergillus fumigatus 1-week culture filtrate, which is rich in the non-glycosylated allergen Asp f1, a major allergen in allergic bronchopulmonary aspergillosis (ABPA). A comparison of the effect of treatment of allergen challenged mice by intranasal administration of a 60-kDa truncated recombinant form of human SP-D (rfhSP-D) or recombinant full length SP-A (rhSP-A) was undertaken. Treatment with rfhSP-D produced significant reduction in IgE, IgG1 and peripheral blood eosinophilia and treatment with rfhSP-D, but not rhSP-A resulted in a significant reduction in airway hyperresponsiveness as measured by whole body plethysmography. Lung histology revealed less peribronchial lymphocytic infiltration in mice treated with rfhSP-D. Intracellular cytokine staining of spleen homogenates showed increases in IL-12 and IFN-gamma and decrease in IL-4. The level of endogenous mouse SP-D was elevated sixfold in the lungs of sensitized mice and was not affected by treatment with rfhSP-D. Taken with our previous studies, with a BALB/c mouse model of ABPA using a 3-week A. fumigatus culture filtrate, the present results show that rfhSP-D can suppress the development of allergic symptoms in sensitized mice independent of genetic background and using a different preparation of A. fumigatus allergens.

Administration, Intranasal↗

PubMed2000

Control of a methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit by unselective use of nasal mupirocin ointment.

In September 1996, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) colonization occurred in the neonatal intensive care unit (NICU) of our hospital. After failing to control the outbreak by conventional methods we implemented an intranasal blanket use programme of mupirocin ointment from the beginning of November 1997. In the programme, patients who had been carrying MRSA received intranasal administration of the ointment three times daily for the first three days and consecutively three times weekly, while newly admitted patients and those who had not been colonized were prophylactically medicated three times weekly. This blanket administration was executed for one month. Methicillin-resistant Staphylococcus aureus colonization became undetectable in all but one intubated inpatient who had already been colonized before the start of the programme, and no new acquisitions occurred until the middle of January 1998, seven weeks after the termination of the blanket use programme. The rate of colonized patients in the unit also decreased. During and after the programme, neither an increase in minimum inhibitory concentration for the antibiotic nor apparent adverse reactions in any of the treated patients were observed. We concluded that this procedure is an effective method of controlling an MRSA outbreak in an NICU when the outbreak cannot be managed with conventional measures.

Administration, Intranasal↗

PubMed2004

Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity.

We investigated the contributions of the structural proteins of severe acute respiratory syndrome (SARS) coronavirus (CoV) to protective immunity by expressing them individually and in combinations from a recombinant parainfluenza virus (PIV) type 3 vector called BHPIV3. This vector provided direct immunization of the respiratory tract, the major site of SARS transmission, replication, and disease. The BHPIV3/SARS recombinants were evaluated for immunogenicity and protective efficacy in hamsters, which support a high level of pulmonary SARS-CoV replication. A single intranasal administration of BHPIV3 expressing the SARS-CoV spike protein (S) induced a high titer of SARS-CoV-neutralizing serum antibodies, only 2-fold less than that induced by SARS-CoV infection. The expression of S with the two other putative virion envelope proteins, the matrix M and small envelope E proteins, did not augment the neutralizing antibody response. In absence of S, expression of M and E or the nucleocapsid protein N did not induce a detectable serum SARS-CoV-neutralizing antibody response. Immunization with BHPIV3 expressing S provided complete protection against SARS-CoV challenge in the lower respiratory tract and partial protection in the upper respiratory tract. This was augmented slightly by coexpression with M and E. Expression of M, E, or N in the absence of S did not confer detectable protection. These results identify S among the structural proteins as the only significant SARS-CoV neutralization antigen and protective antigen and show that a single mucosal immunization is highly protective in an experimental animal that supports efficient replication of SARS-CoV.

Administration, Intranasal↗

PubMed2004

A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs.

A vaccine that would engage the mucosal immune system against a broad range of HIV-1 subtypes and prevent epithelial transmission is highly desirable. Here we report fusing the mucosal targeting B subunit of cholera toxin to the conserved galactosylceramide-binding domain (including the ELDKWA-neutralizing epitope) of the HIV-1 gp41 envelope protein, which mediates the transcytosis of HIV-1 across the mucosal epithelia. Chimeric protein expressed in bacteria or plants assembled into oligomers that were capable of binding galactosyl-ceramide and G(M1) gangliosides. Mucosal (intranasal) administration in mice of the purified chimeric protein followed by an i.p. boost resulted in transcytosis-neutralizing serum IgG and mucosal IgA responses and induced immunological memory. Plant production of mucosally targeted immunogens could be particularly useful for immunization programs in developing countries, where desirable product traits include low cost of manufacture, heat stability, and needle-free delivery.

AIDS Vaccines↗

PubMed1996

Induction of mucosal immune responses against a heterologous antigen fused to filamentous hemagglutinin after intranasal immunization with recombinant Bordetella pertussis.

Live vaccine vectors are usually very effective and generally elicit immune responses of higher magnitude and longer duration than nonliving vectors. Consequently, much attention has been turned to the engineering of oral pathogens for the delivery of foreign antigens to the gut-associated lymphoid tissues. However, no bacterial vector has yet been designed to specifically take advantage of the nasal route of mucosal vaccination. Herein we describe a genetic system for the expression of heterologous antigens fused to the filamentous hemagglutinin (FHA) in Bordetella pertussis. The Schistosoma mansoni glutathione S-transferase (Sm28GST) fused to FHA was detected at the cell surface and in the culture supernatants of recombinant B. pertussis. The mouse colonization capacity and autoagglutination of the recombinant microorganism were indistinguishable from those of the wild-type strain. In addition, and in contrast to the wild-type strain, a single intranasal administration of the recombinant strain induced both IgA and IgG antibodies against Sm28GST and against FHA in the bronchoalveolar lavage fluids. No anti-Sm28GST antibodies were detected in the serum, strongly suggesting that the observed immune response was of mucosal origin. This demonstrates, to our knowledge, for the first time that recombinant respiratory pathogens can induce mucosal immune responses against heterologous antigens, and this may constitute a first step toward the development of combined live vaccines administrable via the respiratory route.

Adhesins, Bacterial↗

PubMed1999

Antigen-specific modulation of experimental myasthenia gravis: nasal tolerization with recombinant fragments of the human acetylcholine receptor alpha-subunit.

Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are antibody-mediated autoimmune diseases in which the nicotinic acetylcholine receptor (AcChoR) is the major autoantigen. The immune response in these diseases is heterogeneous and is directed to a wide variety of T and B cell epitopes of AcChoR. Candidate molecules for specific immunotherapy of MG should, therefore, have a broad specificity. We used recombinant fragments of the human AcChoR, encompassing the extracellular domain of the alpha-subunit, or shorter fragments derived from it, in experiments to modulate EAMG. We have demonstrated that intranasal administration of these recombinant fragments, which represent a major portion of epitopes involved in MG, prevents the induction of EAMG in rats and immunosuppresses an ongoing disease, as assessed by clinical symptoms, weight loss, and muscle AcChoR content. These effects on EAMG were accompanied by a marked reduction in the proliferative T-cell response and IL-2 production in response to AcChoR, in reduced anti-self AcChoR antibody titers and in an isotype switch of AcChoR-specific antibodies, from IgG2 to IgG1. We conclude that nasal tolerance induced by appropriate recombinant fragments of human AcChoR is effective in suppressing EAMG and might possibly be considered as a therapeutic modality for MG.

Administration, Intranasal↗

PubMed2006

Aryl hydrocarbon receptor- and calcium-dependent induction of the chemokine CCL1 by the environmental contaminant benzo[a]pyrene.

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed immunotoxic environmental contaminants well known to regulate expression of pro-inflammatory cytokines such as interleukine-1beta and tumor necrosis factor-alpha. In the present study, we demonstrated that the chemokine CCL1, notably involved in cardiovascular diseases and inflammatory or allergic processes, constitutes a new molecular target for PAHs. Indeed, exposure to PAHs such as benzo[a]pyrene (BP) markedly increased mRNA expression and secretion of CCL1 in primary human macrophage cultures. Moreover, intranasal administration of BP to mice enhanced mRNA levels of TCA3, the mouse orthologue of CCL1, in lung. CCL1 induction in cultured human macrophages was fully prevented by targeting the aryl hydrocarbon receptor (AhR) through chemical inhibition or small interfering RNA-mediated down-modulation of its expression. In addition, BP and the potent AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin were found to enhance activity of a CCL1 promoter sequence containing a consensus xenobiotic-responsive element known to specifically interact with AhR. Moreover, 2,3,7,8-tetrachlorodibenzo-p-dioxin triggered AhR binding to this CCL1 promoter element as revealed by chromatin immunoprecipitation experiments and electrophoretic mobility shift assays. In an attempt to further characterize the mechanism of CCL1 induction, we demonstrated that BP was able to induce an early and transient increase of intracellular calcium concentration in human macrophages. Inhibition of this calcium increase, using the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester or the calcium store-operated channel inhibitor 2-aminoethoxydiphenyl borate, fully blocked CCL1 up-regulation. Taken together, these results bring the first demonstration that PAHs induce expression of the chemokine CCL1 in an AhR- and calcium-dependent manner.

Administration, Intranasal↗