SEARCH · PubMed Health

Results for “Administration, Intranasal”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

PubMed2005

Intranasal administration of ACTH(1-24) stimulates catecholamine secretion.

Previously, we reported that intranasal (IN) ACTH(1-24) administration stimulates adrenocortical steroid secretion in normal subjects. To determine the efficiency of transmucosal absorption of ACTH into the adrenal medulla, we measured serum cortisol, aldosterone, epinephrine, norepinephrine and dopamine levels after IN vs. intravenous (IV) administration of 250 microg ACTH(1-24) in 7 healthy adult men (mean age 21.7 +/- 1.2 yr; range, 21 - 24 yr). Blood was collected at 0, 30, 60 and 120 min after administration of ACTH(1-24), and the levels of adrenocortical steroids and catecholamines were measured by specific RIA and HPLC methods, respectively. There were no side effects associated with IN or IV ACTH administration. Consistent with the previous study, serum cortisol and aldosterone increased after IN administration of ACTH(1-24), peaking 30 min after administration. Sixty minutes after IN and IV administration of ACTH, epinephrine levels increased by 41.9 +/- 13.1 % and 63.3 +/- 11.8 %, respectively, and remained elevated throughout the sampling period. Thirty minutes after IN or IV administration of ACTH(1-24), plasma norepinephrine levels increased by 55.9 +/- 13.4 % and 73.7 +/- 15.0 %, respectively, peaking 30 min after ACTH(1-24) administration, and decreasing to basal levels within 60 min. Plasma dopamine levels did not change after IN administration of ACTH(1-24). Adrenocortical steroid and catecholamine levels did not increase after IN administration of saline. These results demonstrate that IN administration of ACTH(1-24) not only stimulates adrenocortical steroids, but also epinephrine and norepinephrine.

Administration, Intranasal↗

PubMed1972

Interferon in nasal secretions and sera of calves after intranasal administration of avirulent infectious bovine rhinotracheitis virus: association of interferon in nasal secretions with early resistance to challenge with virulent virus.

Calves which had received avirulent infectious bovine rhinotracheitis virus (AV-IBR) by intranasal (IN) administration developed detectable levels of interferon (IF) in nasal secretions as early as 40 hr later. Peak titers (1:640) of IF appeared in secretions 72 to 96 hr after administration of virus, and titers of 1:80 to 1:320 were maintained through the 8th day. Lower titers (1:5 to 1:10) of IF were detected in sera obtained on the 4th to 8th days after administration of virus. Peak titers of IF in respiratory tract secretions were accompanied by a 100- to > 1,000-fold reduction in the levels of AV-IBR present in the secretions. Serum antibody was not detected prior to the 8th day after administration of AV-IBR. Calves which received AV-IBR by the IN route 72 or 96 hr earlier were refractory to challenge with virulent infectious bovine rhinotracheitis virus (IBR), whereas calves receiving AV-IBR 18 or 40 hr earlier became clinically ill following challenge. The temporal association between appearance of IF in respiratory tract secretions and onset of protection against challenge suggests a cause and effect relationship. No IF was detected in either nasal secretions or sera of calves receiving modified IBR virus by intramuscular injection. Following subsequent IN challenge of these calves, IF was detected in nasal secretions as early as 24 hr postchallenge and was maintained at titers of 1:40 to 1:80 for approximately 4 days, even in the absence of virus recovery. Greater ease of local IF induction with IBR virus in calves previously sensitized with that virus is suggested.

Administration, Intranasal↗

PubMed1997

Pharmacokinetic comparison of intravenous and intranasal administration of oxycodone.

BACKGROUND: For patients with chronic pain, treatment with oral analgesics is considered most convenient and feasible. Sometimes, however, the oral route cannot be used because of difficulties with swallowing, nausea, vomiting and gastrointestinal obstruction. To investigate the applicability of the nasal route for the administration of oxycodone, we studied the intravenous and intranasal pharmacokinetics of oxycodone in healthy volunteers. METHODS: Ten healthy volunteers (3 males and 7 females) were given either an intravenous bolus of oxycodone hydrochloride 0.05 mg/kg or nasal sprays of oxycodone hydrochloride 0.1 mg/kg in a cross-over manner. Blood was sampled and subjective effects and side effects were recorded for 10 h. RESULTS: After intravenous administration of oxycodone, the plasma clearance of oxycodone was 0.83 +/- 0.33 l/min (mean +/- SD) and the volume of distribution at steady-state 2.02 +/- 1.47 l/kg and the terminal elimination half-life 157 +/- 47 min. After intranasal administration, peak plasma concentration of oxycodone was 13 +/- 6 ng/ml and it was reached in the median time of 25 min. The intranasal bioavailability of oxycodone was 0.46 +/- 0.34. No clinically significant changes in blood pressure or heart rate were observed but all subjects experienced somnolence after both modes of administration. CONCLUSIONS: The results of this study show that oxycodone is rapidly and rather effectively absorbed from the nasal mucosa but the interindividual differences are large. The intranasal route may in some cases be an attractive alternative to oral or parenteral administration of opioid analgesics. However, because of large interindividual differences, it is prudent to titrate the dose of intranasal oxycodone individually.

Administration, Intranasal↗

PubMed2002

Intranasal administration of a synthetic lipopeptide without adjuvant induces systemic immune responses.

Parenteral injection of a lipopeptide containing a human leucocyte antigen (HLA)-A*0201-restricted cytotoxic T-lymphocyte (CTL) epitope from the human cytomegalovirus (HCMV) immunodominant matrix protein pp65 efficiently induces systemic CTL responses in HLA-A*0201 transgenic mice. In this study, we demonstrate that intranasal (i.n.) administration of this lipopeptide, covalently linked to a universal T helper (Th) epitope (PADRE), also induces potent systemic CTL responses. Immune responses were substantially reduced when the unlipidated peptide analogue was used (P<0.01). The induced CTL were CD8+, major histocompatibility complex (MHC) class I-restricted and CMV specific. Moreover, i.n. administration of this lipidated peptide elicited both systemic and local mucosal CD4+ T-cell proliferative responses, as well as antigen-specific delayed type hypersensitivity (DTH) immune responses. In contrast, mice receiving the unlipidated peptide analogue developed substantially reduced Th or DTH responses (P<0.05). These results highlight the usefulness and potential of lipopeptides delivered via mucosal routes as painless, safe, and non-invasive vaccines.

Administration, Intranasal↗

PubMed2004

Manipulating central nervous mechanisms of food intake and body weight regulation by intranasal administration of neuropeptides in man.

Maintaining a stable body weight set-point is assumed to rely on a homeostatic central nervous system (CNS) regulation of body fat with the particular involvement of hypothalamic pathways. The peripheral adiposity signals insulin and leptin convey information on the amount of energy stored as body fat to the arcuate nucleus of the hypothalamus, where anabolic/orexigenic and catabolic/anorexigenic pathways interact to regulate food intake and energy expenditure. One of the most prominent orexigenic messengers is neuropeptide Y (NPY), whereas melanocortins, including alpha-melanocyte-stimulating hormone (alpha-MSH), are essential for inducing anorexigenic effects. The melanocortin receptor 4 (MC4-R) plays the most important role in mediating catabolic effects of alpha-MSH. In this review, we present a series of own studies on NPY, insulin and MSH/ACTH4-10, an MC4-R agonist. The studies were all based on the intranasal route of administration which enables a direct access of the peptides to hypothalamic functions. NPY acutely attenuated electrocortical signs of meal-related satiety. Prolonged intranasal administration of insulin as well as of MSH induced weight loss in healthy human subjects. However, overweight subjects did not lose body fat after MSH administration. The results corroborate in humans the significance of all three messengers for the central nervous regulation of adiposity and might contribute to the future development of medical strategies against body-weight-related disorders.

Administration, Intranasal↗

PubMed2002

[Adaptive behavior of active and passive rats after intranasal administration of the corticotropin-releasing hormone].

Behavioural effect of intranasal application of corticotropin-releasing hormone (CRH) was investigated in rats with high (KHA) and low (KLA) rate of learning in "open field" and plus-maze (PM) active avoidance test. The neurohormone provoked the opposed changes in behaviour of rats of this strain in both tests. The level of locomotion and exploratory activity rose in KLA rats and decreased in KHA rats. After the CRH application, the KLA rats but not KHA rats spent more time in the opened alleys of the PM than the control animals. The same behavioural changes were observed in our previous research when CRH was injected in striatum. We suppose that CRH is an endogenous factor of precise correction of the adaptive behaviour.

Adaptation, Physiological↗

PubMed2003

Development and in vitro evaluations of gelatin A microspheres of ketorolac tromethamine for intranasal administration.

Gelatin A microspheres (MS) of ketorolac tromethamine (KT) for intranasal systemic delivery were developed with the aim to avoid gastro-intestinal complications, to improve patient compliance, to use as an alternative therapy to conventional dosage forms, to achieve controlled blood level profiles, and to obtain improved therapeutic efficacy in the treatment of postoperative pain and migraine. Gelatin A microspheres were prepared using the emulsification-crosslinking technique. The drug was dispersed in polymer gelatin and formulated into a w/o emulsion with liquid paraffin, using glutaraldehyde as a crosslinking agent. The formulation variables were drug loading and the concentrations of polymer (gelatin), co-polymer (chitosan) and the crosslinking agent. All the prepared microspheres were evaluated for physical characteristics, such as particle size, incorporation efficiency, swelling ability, in vitro bioadhesion on rabbit small intestine and in vitro drug release characteristics in pH 6.6 phosphate buffer. All the microspheres showed good bioadhesive properties. Gelatin A and chitosan concentrations, percentage of the crosslinking agent and also the drug loading affected significantly the rate and extent of drug release. The data indicated that the KT release followed Higuchi's matrix model.

Adhesiveness↗

PubMed2000

Effect of intranasal administration of Lactobacillus fermentum on the respiratory tract of mice.

This paper studied the effect of intranasal inoculation of Lactobacillus fermentum, a microorganism belonging to the normal flora of the mouse pharynx, on the respiratory tract of mice. Optimal temporary colonization in different areas of the tract was obtained through administration of 4 times a dose of 5 x 10(7) CFU. L. fermentum remained in the trachea and bronchi up to the 7th day after inoculation. Re-inoculation of lactobacilli on the 10th day produced a transient colonization of the respiratory tract. Histological modifications produced in the trachea were mainly observed as an increased lymphocyte population at sub-mucosa level on the 4th day after inoculation. There was an increased number of activated macrophages in cytological slides of lung tissues on days 2 and 4. Re-inoculation also produced stimulation of the G2 macrophages on days 12, 14 and 17. From a histological point of view there were no other important changes in the organs studied. These results suggest stimulation of the immune system, especially that of the mucosal surfaces, after intranasal administration of L. fermentum in the experimental model employed. Stimulation was reflected in tracheal lymphocyte proliferation and increased lung macrophage population which have to be further studied in more detail.

Administration, Intranasal↗

PubMed2006

Delivery of 125I-cobrotoxin after intranasal administration to the brain: a microdialysis study in freely moving rats.

In order to determine the contribution of intranasal (i.n.) administration to the uptake of large molecular weight (MW) substances into central nervous system (CNS), concentration in brain of the centrally acting polypeptide cobrotoxin (NT-I) versus time profiles were studied using dual-probe microdialysis in awake free-moving rats. NT-I, radiolabeled with sodium (125)I-Iodide ((125)I-NT-I), was administered at the dose of 105 microg/kg intravenously and intranasally in the same set of rat (n=15). The (125)I-NT-Inasal preparations were formulated with borneol/menthol eutectic mixture (+BMEM) as an absorption enhancer and without (-BMEM). After application, the dialysates sampled simultaneously from olfactory bulb and cerebellar nuclei were measured in a gamma-counter for radioactivity. The real concentrations of NT-I were recalculated by in vivo recoveries of microdialysis probes. The results showed that the area under the curve (AUC) value in cerebellar nuclei (2283.51+/-34.54 min ng/ml) following i.n. administration (+BMEM) was significantly larger than those (AUC(olfactory)=1141.92+/-26.42 min ng/ml; AUC(cerebellar)=1364.62+/-19.35 min ng/ml) after intravenous (i.v.) bolus, respectively. A prolonged time values to peak concentrations after i.n. application (+BMEM) were observed compared with those following i.v. administration. Also, following i.n. application (+BMEM) the measured time value to peak concentration in cerebellar nuclei (85 min) was statistically longer than that in olfactory bulb (75 min), which could be plausibly an indication for NT-I delivery into brain via nose-brain pathway in the presence of absorption enhancer. i.n. administration (-BMEM) had little or no ability of NT-I delivering into brain. In conclusion, i.n. administration (+BMEM) significantly enhanced brain transport of NT-I with uneven distribution in discrete regions of brain compared with i.v. administration. Additionally, multi-probe microdialysis technique should be considerably valuable in brain delivery studies.

Administration, Intranasal↗

PubMed1999

Intranasal administration of retinal antigens induces transient T cell activation and apoptosis within drainage lymph nodes but not spleen.

Mechanisms of mucosal tolerance induction, including anergy/deletion and active suppression are frequently described as mutually exclusive; dependent upon nature, dose and route of antigen administration. We have previously described induction of low-dose tolerance with administration of retinal autoantigens via the nasorespiratory tract which is antigen-specific, suppresses both cell mediated immunity and ultimately tissue destruction in experimental autoimmune uveoretinitis (EAU) and is mediated by splenic-derived regulatory cells. The present data further shows that splenocytes or fractionated splenic T cells, which secrete IL-4 and IL-10 when stimulated with retinal antigen in vitro, and not regional drainage lymph node cells transfer tolerance to naïve animals. Analysis of apparent mechanistic differences shows that during intranasal antigen administration, the proportion of CD4(+)T cells within drainage lymph nodes increases, concurrent with a burst of IFN-gamma. Following subsequent antigen challenge, T cells downregulate alphabetaTCR expression and undergo apoptosis in regional drainage lymph nodes. An increase in functional Th2 cytokine activity was noted in both Con-A and retinal antigen stimulated lymph node cultures in tolerized animals. T cells from tolerized animals secreted IL-4, whereas IL-10 was secreted predominantly by the non-T cell population present equally in control and tolerized animals. Therefore, spleen derived regulatory cells which suppress Th1 responses and T cell deletion/apoptosis in regional drainage lymph nodes are mechanisms which co-exist in tolerant rats. Th2 cytokine production after immunization appears consequential to tolerance-induced Th1 suppression.

Administration, Intranasal↗

PubMedDate not supplied

Intranasal administration of a Pseudomonas lipopolysaccharide vaccine in cystic fibrosis patients.

A purified lipopolysaccharide Pseudomonas aeruginosa vaccine was administered via intranasal spray to cystic fibrosis patients in an attempt to induce development of local antibody without the side effects associated with parenteral administration of the vaccine. Although slight increases in serum antibody titers were noted, there was no appreciable change in specific antibody levels in parotid saliva or sputum following intranasal administration of the vaccine.

Administration, Intranasal↗

PubMed2001

A combination of interleukin-2 and 60 nm cationic supramolecular biovectors for the treatment of established tumours by subcutaneous or intranasal administration.

The Supramolecular Biovector (SMBV) KY is a drug delivery nanocarrier which consists of a discretely sized, ionically charged, cross-linked polysaccharide core surrounded by a lipid membrane. We used the non-immunogenic spontaneous mammary adenocarcinoma TS/A tumour to test the efficacy on tumour growth of low (10(4) IU) or ultra-low (10(3) IU) doses of interleukin-2 (IL-2) adsorbed to these 60 nm cationic synthetic particles. In comparison with the progressive growth of TS/A cells in syngeneic mice, KY/IL-2 particles coinjected with TS/A cells or administered at a distance from the tumour, inhibited tumour growth while free IL-2, even at 10-100 times the dose used in the KY/IL-2 formulations, had no effect. Studies performed on implanted tumours (treatment at day 6 (D6)) showed that KY/IL-2 administered subcutaneously (s.c.) at five sites distant from the tumour (10(3) IL-2 IU per site) induced rejection of the implanted tumours. Six out of 10 mice were cured while the other four had residual tumours only. In the same experiment, free IL-2 induced only tumoral growth reduction. Protection induced by KY/IL-2 administered s.c. at five sites involved recruitment of a CD8(+) T cell response since nu/nu mice and CD8-depleted mice did not reject the tumours. Mice cured were protected significantly to completely against a rechallenge with TS/A tumour cells, and a systemic tumour-specific CTL activity was induced. Finally, we showed that repeated intranasal (i.n.) administration of KY/IL-2 (low-dose) also led to complete regression of pre-established tumours and partial protection from tumour rechallenge. We therefore suggest that, in contrast to free IL-2, a KY/IL-2 formulation could be used as a systemic immunostimulant leading to the eradication of non-immunogenic, established tumours.

Adenocarcinoma↗

PubMed2006

Induction of systemic and mucosal immune responses by intranasal administration of alginate microspheres encapsulated with tetanus toxoid and CpG-ODN.

In the induction of systemic and mucosal immunity, particulate antigens are more effective than soluble antigens; possibly because they are more efficiently endocytosed by mucosal-associated lymphoid tissue (MALT) M cells. In this study, we determined the systemic and mucosal immune responses in rabbits following intranasal immunization with encapsulated tetanus toxoid (TT) and CpG-ODN in alginate microspheres. The microspheres were less than 4 microm in diameter. Encapsulation efficiency of TT and CpG-ODN was determined as 47.7+/-6.6 and 34.2+/-7.4, respectively. Release of TT and CpG-ODN in a simulated model with nasal cavity was 14.2+/-3.06 and 36.7+/-2.4% after 4 h. Encapsulated TT preserved its intact structure, but its immunoreactivity was decreased to about 91+/-5%. The highest serum IgG and antitoxin, and nasal lavage IgA titers were observed in groups immunized with microsphere formulations. CpG-ODN as an adjuvant could increase the serum IgG and antitoxin titers when co-administered with TT solution, but its co-encapsulation with TT in alginate microspheres failed to potentiate the systemic immune response while induced high IgA titers in nasal lavages. No hemolysis was occurred on incubation of alginate microspheres and human RBCs. Also after nasal administration of plain microspheres to human volunteers, no local irritation was observed. Intranasal administration of microspheres encapsulated with vaccines showed to be an effective way for inducing a variety of immune responses and that a strong systemic IgG and mucosal IgA responses can be induced in rabbits with intranasal administration of alginate microspheres encapsulated with TT.

Adjuvants, Immunologic↗

PubMed2002

Size dependent immune response after subcutaneous, oral and intranasal administration of BSA loaded nanospheres.

BSA was entrapped in particles of different sizes (200, 500 and 1000 nm) prepared from poly(D,L-lactic-co-glycolic) acid by a double emulsion method. The particles were given, either intranasally, orally or subcutaneously, to Balb/c mice and the serum IgG, IgG1 and IgG2a response elicited was compared to that obtained by the subcutaneous administration of either free antigen, free antigen emulsified 1:1 with Freund's Complete Adjuvant (FCA), or free antigen administered with Al(OH)(3). The administration of 1000 nm particles generally elicited a higher serum IgG response than that obtained with the administration of 500 or 200 nm sized nanospheres, the immune response for 500 nm particles being similar than that obtained with 200 nm by the subcutaneous and the oral route, and higher by the intranasal route. PLGA nanoparticles can elicit serum IgG2a responses by the three routes studied. No significant differences on the serum IgG2a/IgG1 ratios were found after the subcutaneous, the oral and the intranasal administration of the different spheres but those were in general higher compared to the administration of either free antigen or free antigen adsorbed to alum. The route of administration influences the serum IgG2a/IgG1 ratio after the administration of free antigen, but not after the administration of the particles. Therefore, differences on the total serum IgG response induced by particles of different sizes do not result in differences on the IgG1 or IgG2a-type immune responses, suggesting that the antigen processing and presentation is similar in all cases tested for PLGA particles.

Administration, Intranasal↗

PubMed1995

Pharmacokinetics and pharmacodynamics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following intranasal administration in rabbits.

The objective of this study was to evaluate the pharmacokinetics and pharmacodynamics of G-CSF as well as their relationship following intranasal (i.n.) administration of aqueous rhG-CSF preparations with or without additives. In order to achieve a better understanding of the dosage regimen and the effectiveness of intranasally administered rhG-CSF in inducing leukopoiesis, we investigated rhG-CSF absorption and blood leukocyte dynamics with respect to dose in rabbits. RhG-CSF could be absorbed through the nasal cavity of rabbits when rhG-CSF aqueous preparations, especially those containing alpha-cyclodextrin (alpha-CyD) were intranasally administered. We found that serum G-CSF levels and the total count of leukocytes in peripheral blood (total blood leukocyte count) showed a dose-dependent increase with rhG-CSF. The area under the serum G-CSF concentration-time curve (AUC, a pharmacokinetic parameter) and the area under the increased total blood leukocyte count-time curve (AUL, a pharmacodynamic parameter) increased with increase of dose of rhG-CSF administered intranasally. Good agreement was observed between log AUC and AUL; thus, it is concluded that an increase of AUC leads to an increase in effectiveness of rhG-CSF in inducing leukopoiesis in rabbits. A novel rhG-CSF delivery system in the form of i.n. administration of rhG-CSF was thus achieved.

Administration, Intranasal↗

PubMed1986

Intranasal administration of beta-interferon in rabbits.

beta-Interferon (IFN) administered intranasally in solution or as a powder without surfactants was not absorbed in rabbits. However, absorption occurred after the addition of surfactants (non-ionic, anionic and amphoteric). Maximum concentrations of IFN in plasma were dependent on the surfactant used, sodium glycocholate being the most effective. Total absorption of IFN following nasal administration with sodium glycocholate was 2.2% of that following intravenous administration.

Administration, Intranasal↗

PubMed1994

Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin).

OBJECTIVE: Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS: Ten children with familial short stature (FSS) aged 5.5-15.5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS: All 12 subjects were submitted to i.v. (1 microgram/kg) and i.n. (20 micrograms/kg) hexarelin tests with a one-week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio-immunoassays (RIA). RESULTS: Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (+/- SD) being 72.2 +/- 35.5 mU/l for the i.n. test and 79.6 +/- 53.0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15-30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response in either test. Plasma TSH decreased in the FSS children from a mean (+/- SD) of 1.0 +/- 0.26 to 0.64 +/- 0.2 mU/l (P < 0.005) during the i.n. test and from 1.0 +/- 0.3 to 0.7 +/- 0.3 mU/l (P < 0.05) during the i.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1.06 +/- 0.38 mU/l to 0.86 +/- 0.17 during the i.v. test and from 1.60 +/- 0.01 to 1.11 +/- 0.06 mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS: The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intranasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.

Administration, Intranasal↗

PubMed1983

Intranasal administration of gentamicin in human subjects.

The effectiveness of gentamicin administered by the intranasal route in healthy human volunteers was studied. Thirty minutes after gentamicin in a solution of 1% sodium glycocholate was administered at 2 mg/kg of body weight, gentamicin concentrations of 2.48 +/- 0.42 mg/ml were present in the sera. Serum concentrations decreased to 0.94 +/- 0.13 mg/ml at 180 min. No serious side effects were observed. There was slight local irritation after a single dose. When administered intranasally without glycocholate, gentamicin was not present in the sera in detectable amounts.

Administration, Intranasal↗