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Results for “Administration, Intranasal”

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PubMed2006

The encapsulation of enterotoxigenic Escherichia coli colonization factor CS3 in biodegradable microspheres enhances the murine antibody response following intranasal administration.

The aim of this study was to measure serum and mucosal antibody responses following intranasal administration of biodegradable poly(DL-lactide-co-glycolide) (PLGA) microspheres loaded with the CS3 colonization factor isolated from enterotoxigenic Escherichia coli (ETEC). The response was compared against that measured in mice similarly administered the native CS3 antigen and in mice co-administered, along with the CS3 antigen, a known mucosal adjuvant, the R192G mutant heat-labile enterotoxin (mLT). The integrity of the CS3 antigen released from the microspheres was maintained as determined by SDS-PAGE and immunoblotting. Native CS3 induced serum and mucosal (bronchoalveolar, small intestinal and faecal) IgG and IgA responses. The co-administration of the mLT mucosal adjuvant significantly enhanced (P<0.001) serum and mucosal antibody responses to the CS3 protein. Likewise, the CS3-loaded PLGA microspheres induced significantly greater (P<0.001) serum and mucosal antibody responses than native CS3, as well as inducing antibody responses superior to those of the CS3 plus mLT formulation. Following administration of CS3 plus mLT, the mice became distressed (loss of activity, increased huddling, ruffled fur), a situation not seen following administration of the CS3-loaded PLGA microspheres. The results in this trial show that the CS3-loaded PLGA microspheres when administered intranasally to mice caused no observable distress to the mice and significantly (P<0.001) enhanced the immunogenicity of the CS3 protein.

Adjuvants, Immunologic↗

PubMed2003

[Immunopotency of the recombinant urease B subunit vaccine of Helicobacter pylori after intranasal administration to mice].

AIM: To observe the immunopotency of the recombinant urease B subunit (rUreB) of Helicobacter pylori after intranasal administration to mice. MDTHODS: BALB/c mice were immunized intranasally with rUreB of 20 microg,10 microg and rUreB plus different adjuvants, such as cholera toxin B subunit (CTB), Escherichia coli heat labile enterotoxin B subunit (LTB) and carbopol respectively, four times at an intervals of 7 days. The serum and washing solution from gastric, intestinal, nasal and tracheal mucosas were collected in 7 days after final immunization. IgG and IgA antibodies specific for rUreB were detected by ELISA. RESULTS: The levels of IgA and IgG antibodies in sera every groups of mice immunized intranasally were significantly increased compared with control group (P<0.01). Only the levels of serum IgG of mice immunized with 20 microg dose were higher than those of mice immunized with 10 microg dose. Carbopol could enhance the level of IgA antibodies in washing solution from mouse gastric mucosa after intranasal immunization. The efficacy of LTB as a nasal mucosal immuno-adjuvant was stronger than that of CTB. CONCLUSION: CTB, LTB and carbopol can play the role of adjuvant in nasal mucosal immunization. Intranasal immunization with rUreB can induce not only serum IgG antibody production but also antibody responses of different mucosa. Thus intranasal inoculation is a convenient, effective and cheap immunization way.

Acrylic Resins↗

PubMed1986

[Effects of intranasal administration of LHRH superanalogue on endogenous LHRH and gonadotropins in humans].

Plasma LH, FSH and endogenous LHRH were determined by radioimmunoassay (RIA) when 100 micrograms of LHRH superanalogue, des-Gly10-[D-Leu6]-LHRH ethylamide (leuprolide) was intranasally administered to both 7 healthy subjects aged 22 to 63 years and 6 patients with various hypogonadism aged 22 to 43 years [2 with anorexia nervosa, 3 with hypophysial hypogonadism and 1 with isolated gonadotropin (Gn) deficiency]. The response of plasma LH after the intranasal administration of leuprolide was observed to be 814 +/- 236 (mean +/- SE)% in the healthy subjects at 2 to 10 hours, and 528 +/- 183% in the patients with hypogonadism at 2 to 4 hours. These elevations were observed until 24 hours after administration in both groups. The response of plasma FSH was observed to be 449 +/- 99% in the healthy subjects at 3 to 8 hours, and 593 +/- 238% in the patients with hypogonadism at 2 to 6 hours. These elevations were observed until 24 hours in the healthy subjects and until 12 hours in the patients with hypogonadism. Furthermore, these responses tended to be higher than those after 100 micrograms intravenous administration of LHRH; LH responded up to 386 +/- 50% in the healthy subjects and up to 390 +/- 91% in the patients with hypogonadism, and FSH up to 282 +/- 38%, 343 +/- 90%, respectively. The elevation of plasma immunoreactive LHRH which was determined using RIA having no immunocrossreactivity with leuprolide (less than 0.01%) was observed at 6 hours after the administration of leuprolide in the healthy subjects (789 +/- 497%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMed1982

Decreases in ciliary beat frequency due to intranasal administration of propranolol.

Recently the intranasal application of 5% propranolol was proposed in order to prevent the extensive first-pass metabolism of this drug. The ciliary epithelium in the nose affects the removal of dust, allergens, and microorganisms. The decreasing effect of propranolol on the ciliary beat frequency of human adenoid tissue and chicken embryo tracheas was measured with a photoelectric registration device. After nasal application of 5% propranolol, the drop is diluted by the nasal mucus. It was found that even 0.1% propranolol had a deleterious effect on the cilia of chicken and human tissue. Ciliary movement was arrested irreversibly within 20 min.

Adenoids↗

PubMed1995

Effects of intranasal administration of endothelin-1 to allergic and nonallergic individuals.

Endothelin-1 (ET-1), a 21 amino acid peptide, and its receptors are distributed in the mammalian respiratory tract. To examine the responses of human upper airways to ET-1, we investigated the effects of intranasal administration of ET-1 to nine symptomatic allergic and nine nonallergic volunteers. Paper discs were used to administer ET-1 or diluent to one side of the nasal mucosa, and to collect secretions from the ipsilateral (challenged) and contralateral (opposite) nostrils. ET-1 (0.3-10 micrograms), but not diluent, induced dose-dependent bilateral increases in secretion weights, lysozyme secretion, symptoms of rhinorrhea and itch, and sneezing in both populations. ET-1 did not induce albumin secretion, histamine release, or symptoms of nasal congestion. Compared with the nonallergic subjects, allergic individuals sneezed more and had significantly higher bilateral secretion weights, contralateral lysozyme secretion, and symptoms of rhinorrhea following ET-1 provocation. In summary, ET-1 induced symptoms relevant to inflammatory upper airway diseases in allergic and nonallergic subjects. However, responses of allergic subjects were more pronounced, particularly with respect to symptoms associated with neural reflex responses, such as sneezing and contralateral secretion. Therefore, allergic inflammation enhances responsiveness of the nasal mucosa to ET-1.

Administration, Intranasal↗

PubMed2001

Solubilization and stability of bumetanide in vehicles for intranasal administration, a pilot study.

The solubility of bumetanide in vehicles of various polarities, suitable for intranasal administration in acute situations, has been investigated. The solubility at 4 degrees C in glycofurol and polyethylene glycol 200 was high (167 and 143 mg/mL, respectively), decreasing exponentially with addition of phosphate buffer or coconut oil. Vehicles containing coconut oil and glycofurol did not seem to improve the solubility relative to mixtures between glycofurol and buffer. Adequate solubility (approximately 50 mg/mL) was achieved in vehicles containing about 80% cosolvent. The stability of bumetanide was studied at 5 degrees C and 57 degrees C. No degradation was observed at low temperature. At high temperature, bumetanide decomposes in nonaqueous vehicles with half-lifes ranging from 69 to 400 days, but sufficient stability may be obtained by adjustment of pH to 7.4. It may be concluded that it is possible to prepare a clinically relevant formulation for intranasal delivery of bumetanide.

Administration, Intranasal↗

PubMed1999

The effects of dexamethasone on the response of bronchus-associated lymphoid tissue to intranasal administration of formalin-killed Pasteurella haemolytica A2 in goats.

A trial was conducted to observe the immediate and chronic effects in goats of dexamethasone administration on the bronchus-associated lymphoid tissue (BALT) response to intranasal administration of formalin-killed Pasteurella haemolytica A2. Twenty-four goats were divided into four groups. Those in group 1 were injected intramuscularly with 1 mg/kg dexamethasone on three consecutive days, followed by intranasal exposure to formalin-killed P. haemolytica A2 one day after the last dexamethasone treatment. The goats in group 2 were similarly injected with dexamethasone followed by intranasal exposure to formalin-killed P. haemolytica A2 21 days after the last dexamethasone treatment. The animals in group 3 were exposed intranasally to formalin-killed P. haemolytica A2 without prior dexamethasone treatment. The animals in group 4 were untreated controls. The intranasal exposures to formalin-killed P. haemolytica A2 were repeated 2 weeks later. Intranasal exposure to formalin-killed P. haemolytica 1 day after dexamethasone treatment further reduced the number and size of BALT compared to the untreated control. Significantly (p < 0.01) more reduction of BALT occurred in goats exposed to formalin-killed P. haemolytica A2 21 days after dexamethasone treatment. On the other hand, intranasal exposure of goats without prior dexamethasone treatment stimulated the BALT compared to the untreated controls.

Administration, Intranasal↗

PubMed1983

Intranasal administration of nitroglycerine attenuates the pressor response to laryngoscopy and intubation of the trachea.

The intranasal administration of nitroglycerine (NTG) was undertaken in 35 adult female patients 1 min before the induction of anaesthesia. A control group consisting of 32 patients did not receive NTG. Systolic arterial pressure (SAP) and heart rate (HR) were recorded before the induction of anaesthesia and at 0, 3, and 5 min after tracheal intubation. SAP did not increase significantly in the NTG group immediately after intubation, while significant decreases in SAP were observed at 3 and 5 min (P less than 0.005 and P less than 0.001 respectively). SAP did increase significantly in the control group. HR was increased in both groups immediately after intubation (P less than 0.001 and P less than 0.001 respectively). NTG administered intranasally is a safe, simple and effective method to attenuate the hypertensive response to laryngoscopy and tracheal intubation.

Administration, Intranasal↗

PubMed2006

In vivo induction of mucosal immune responses by intranasal administration of chitosan microspheres containing Bordetella bronchiseptica DNT.

In vitro immune-stimulating activities of Bordetella bronchiseptica dermonecrotoxin (BBD)-loaded in chitosan microspheres (CMs) were reported with a mouse alveolar macrophage cell line (RAW264.7). Based on the report, in vivo activity of immune-induction was investigated by intranasal administration of the BBD-loaded CMs into mice. BBD was loaded into the CMs prepared by an ionic gelation process with tripolyphosphate. Mice were immunized by direct administration of the BBD-loaded CMs into the nasal cavity. After immunization of the mice, BBD-specific immune responses (IgG and IgA titers) were measured in sera, nasal wash, and saliva by ELISA. BBD-specific IgA titers in the nasal cavity were time- and dose-dependently increased by the administration. Similar phenomena were observed in the analysis of systemic IgA and IgG in sera. However, the antibody in saliva was undetectable by ELISA. These results suggested that direct vaccination via the nasal cavity was effective for targeting nasal-associated lymphoid tissues, and that CMs were an efficient adjuvant in nasal mucosal immunity for atrophic rhinitis vaccine.

Administration, Intranasal↗

PubMed2004

Transplantation tolerance induced by intranasal administration of HY peptides.

Induction of antigen-specific tolerance to transplantation antigens is desirable to control host-versus-graft and graft-versus-host reactions. Following molecular identification of a set of minor histocompatibility (H) antigens, we have used selected HY peptide epitopes for this purpose. Intranasal administration of individual major histocompatibility complex (MHC) class II-restricted HY peptides induces indefinite survival of syngeneic male skin grafts and allows engraftment of male bone marrow. Tolerance involves linked suppression to additional HY epitopes on test grafts. Long-term tolerance also requires suppression of emerging thymic emigrants. It does not involve deletion. HY peptide-specific CD4(+) and CD8(+) T cells expand on re-exposure to male antigen; these expansions are smaller in tolerant than control mice and fewer HY-specific cells from tolerant females secrete interferon gamma and interleukin 10 (IL-10). Significantly, CD4(+) cells from peptide-pretreated females fail to make IL-2 responses to cognate peptide, limiting expansion of the HY-specific CD8(+) populations that can cause graft rejection. Consistent with this, tolerance induction by HY peptide is abrogated by coadministration of lipopolysaccharide. IL-10 does not appear to be critically involved because tolerance is inducible in IL-10-deficient mice. Adoptive transfer of tolerance into naive neonatal recipients by splenocytes from long-term tolerant donors provides evidence for involvement of regulatory cells.

Administration, Intranasal↗

PubMed1995

Eosinophil infiltration precedes development of airway hyperreactivity and mucosal exudation after intranasal administration of interleukin-5 to mice.

Recently, we demonstrated that antibody to interleukin-5 (IL-5) prevents the infiltration of eosinophils in the respiratory airways and the development of bronchial hyperreactivity in an animal model of allergic asthma. In this study we investigated the influence of long-term intranasal administration of IL-5 on airway responsiveness in vitro, the infiltration of inflammatory leukocytes, and mucosal exudation. Mice (BALB/c) received 1 microgram of recombinant human IL-5 in 30 microliters of saline solution or vehicle alone twice a day for 1, 3, and 7 days. At 3 and 7 days after IL-5 administration, the number of bronchoalveolar lavage eosinophils increased approximately fourfold and sixfold, respectively. Blood eosinophil numbers showed a similar increase. In addition, 7 days after IL-5 treatment, total lung eosinophil peroxidase activity was significantly increased by 170% as compared with controls. The maximal responsiveness of the trachea in vitro to methacholine was significantly increased by 34%, as compared with controls, only at 7 days after IL-5 administration. Furthermore, mucosal exudation was also only increased significantly at 7 days after IL-5 administration. It can be concluded that the IL-5-induced eosinophil infiltration precedes the development of airway hyperreactivity and mucosal exudation.

Administration, Intranasal↗

PubMed1993

Absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and blood leukocyte dynamics following intranasal administration in rabbits.

Absorption of recombinant human granulocyte colony-stimulating factors (rhG-CSF) following intranasal administration of aqueous preparations containing rhG-CSF with or without dimethyl-beta-cyclodextrin was investigated. It was found that rhG-CSF was absorbed and the total leukocyte numbers in peripheral blood markedly increased after intranasal instillation of rhG-CSF solution (pH 4) without excipients. Simultaneously administered dimethyl-beta-cyclodextrin enhanced nasal absorption of rhG-CSF. Consequently, serum rhG-CSF concentrations and total leukocyte numbers were greatly increased.

Administration, Intranasal↗

PubMed2003

Characterization of airway nitric oxide in allergic rhinitis: the effect of intranasal administration of L-NAME.

BACKGROUND: Several studies have attempted to assess nasal nitric oxide (NO) levels in allergic rhinitis (AR). However, there seem to be differences in the results obtained. We therefore wanted to investigate this further by studying airway NO in AR and controls at several modalities, and also the effect of intranasal administration of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine-methyl ester.HCl (L-NAME). METHODS: Airway NO was determined through repeated measurements at three flow rates of air (0.5, 3, and 9 l/min), using a single-breath method and a method of nasal aspiration, in 18 patients with birch pollen AR during season and in 18 controls. RESULTS: Patients with AR were characterized by no difference in nasal but higher orally exhaled NO and a larger interindividual spread in nasal and orally exhaled NO compared to controls. We also found a greater reduction in nasal NO after L-NAME in patients compared to controls. DISCUSSION: These results indicate that several factors determine the levels of nasal NO in rhinitis. NO production in the nasal mucosa of patients with AR may be upregulated. On the other hand, this increase could be counteracted by swelling of the mucosa and secretions resulting in impaired NO diffusion from, for example, the paranasal sinuses, where particularly high levels of NO have been found. Also, the high background levels of NO from constitutive sources in the nose may blunt smaller increases in mucosal NO output. CONCLUSION: It seems that the methods for measurement of nasal NO need to be improved and standardized before we can consider to use this test in monitoring inflammation in AR.

Administration, Intranasal↗

PubMed1997

Pharmacokinetic and pharmacodynamic response after intranasal administration of diazepam to rabbits.

Nasal application of drugs might be an alternative to intravenous administration in acute situations such as epileptic or fever seizures. In the search for a nasal formulation leading to a peak plasma concentration of diazepam at a tmax < or = 5 min bioavailability in rabbits has been studied after intranasal administration of the drug in ten vehicles of different polarity. The animals were dosed with 3 mg diazepam, dissolved in 100 microL vehicle, the solution being administered into both nostrils. The bioavailability, measured during the first 30 min, because periods after this are not relevant for acute treatment, was found to be between 49 and 62% for the four most promising vehicles, pure glycofurol 75, tetraethyleneglycol, poly(ethylene glycol) 200 and 30% glycofurol in tetraethyleneglycol. The tmax for these vehicles was achieved after 5 min, and they induced a very rapid pharmacodynamic response after 1.5 to 3.5 min. The bioavailability was reduced when more polar liquids such as ethanol and tween 20, or lipid oils, e.g. vegetable oil and miglyol 840 were added to the glycofurol. There was a good correlation between tmax and the induction of pharmacodynamic response. These results suggest that nasal application of diazepam in a water-free low-molecular-weight glycol might be of clinical importance as an alternative to intravenous injection, especially in acute situations.

Administration, Intranasal↗

PubMed2000

Inducing tolerance by intranasal administration of long peptides in naive and primed CBA/J mice.

To assess the capacity of a peptide-based immunotherapy to induce systemic tolerance via the nasal route, we designed three long overlapping peptides of 44-60 aa covering the entire sequence of phospholipase A2 (PLA2), a major bee venom allergen. Both prophylactic and therapeutic intranasal administrations of long peptides to PLA2-hypersensitive CBA/J mice induced specific T cell tolerance to the native allergen. In prophylactic conditions, this tolerance was marked by a suppression of subsequent specific IgE response, whereas the therapeutic approach in presensitized mice induced a more than 60% decrease in PLA2-specific IgE. This decline was associated with a shift in the cytokine response toward a Th1 profile, as demonstrated by decreased PLA2-specific IgG1 and enhanced IgG2a levels, and by a decline in the specific IL-4/IFN-gamma ratios. T cell transfer from long peptide-tolerized mice to naive animals abrogated the expected anti-PLA2 IgE and IgG1 Ab response, as well as specific T cell proliferation, but enhanced specific IgG2a response upon sensitization with PLA2. These events were strongly suggestive of a clonal anergy affecting more profoundly Th2 than the Th1 subsets. In conclusion, these results demonstrate that allergen-derived long peptides delivered via the nasal mucosa may offer an alternative to immunotherapy with native allergens without the inherent risk of systemic anaphylactic reactions. Moreover, long peptides, in contrast to immunotherapy strategies based on short peptides, have the advantage of covering all potential T cell epitopes, and may represent novel and safe tools for the therapy of allergic diseases.

Administration, Intranasal↗

PubMed1997

Intranasal administration of IFN-alpha/beta inhibits the development of visceral tumor metastases.

Intranasal administration of 10(4) U of murine interferon (IFN)-alpha/beta prolonged the survival time of DBA/2 mice injected i.v. with 10(5) (> 20,000 LD50) IFN-alpha/beta-resistant 3C18 Friend leukemia cells (FLC). Long-term survivors rejected a second challenge with 3C18 FLC without additional IFN-alpha/beta treatment. IFN-alpha/beta administered intranasally was not effective in 3C18 FLC-challenged DBA/2 mice pretreated with antibody to IFN-alpha/beta. Recombinant human IFN-alpha BDBB, which is cross-reactive on mouse cells, also increased the survival time of 3C18 FLC-challenged DBA/2 mice. Placing 10(4) U IFN-alpha/beta twice a day into the nostrils also prolonged the survival time of DBA/2 mice with 3-day established 3C18 FLC tumors. Administration of 10(4) U IFN-alpha/beta into the nasopharynx was equally effective or more effective than an equivalent amount of IFN-alpha/beta given by the i.p or oral routes or by gavage. Intranasally administered IFN-alpha/beta also increased the survival time of C57B1/6 mice challenged i.v. with EL4 T cell lymphoma cells, DBA/2 mice challenged i.v. with L1210R B cell lymphoma cells, and C57B1/6 (H-2b) and DBA/2 (H-2d) mice challenged i.v. with B16 melanoma cells (H-2b). These results may be important in devising novel therapeutic strategies for malignant disease using type I IFN.

Administration, Intranasal↗

PubMedDate not supplied

[Kinetics of Semax penetration into the brain and blood of rats after its intranasal administration].

The radioactive peptide analogue Semax corresponding to the ACTH(4-10) sequence (Met-Glu-His-Phe-Pro-Gly-Pro) with a molar radioactivity of 56 Ci/mmol labeled with tritium at the C-terminal Pro was prepared. The labeled peptide was used for studying the kinetics of Semax penetration into rat brain and blood after its intranasal administration (50 microg/kg, 20 microl of solution) to nonbred white rats of body mass 200-250 g. It was demonstrated that 0.093% of the total introduced radioactivity per gram can be found in the rat brain 2 min after the administration, 80% of this radioactivity belonged to Semax, and the rest, to its metabolites. The peptide undergoes rapid enzymatic degradation, with the tripeptide Pro-Gly-Pro prevailing in biological samples relative to the total content of Semax and its metabolites.

Administration, Intranasal↗

PubMed1991

Intranasal administration of insulin to humans.

The purpose of this review is to summarize the information and experience at present available on the intranasal administration of insulin to human subjects and to describe some of the anatomical, physiological, pharmaceutical and technological factors which can affect the absorption of insulin. An overview is given of those absorption promoters which have been used in clinical insulin studies, and the possible absorption-promoting mechanisms are discussed. This review shows that the nasal route offers a promising alternative to parenteral administration. The easier administration and the acceptance by the patients is encouraging the development of new intranasal insulin preparations.

Absorption↗