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Results for “Administration, Intranasal”

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PubMed2002

Intranasal administration of plasmid DNA-coated nanoparticles results in enhanced immune responses.

Intranasal immunization offers potential forthe elicitation of effective mucosal and systemic immune responses. In this study, a previously reported novel cationic nanoparticle engineered from a microemulsion precursor was further modified, optimized and applied intranasally to mice to explore its potential as a plasmid DNA (pDNA) vaccine delivery system. To this end, more uniform nanoparticles (around 100 nm) containing less cationic surfactant were developed. The pDNA-coated nanoparticles significantly enhanced the specific serum IgG and IgA titres to an expressed model antigen, beta-galactosidase, by 18-28 and 25-30 fold, respectively, when compared with naked pDNA alone. An enhanced splenocyte proliferative response was also observed after immunization with the pDNA-coated nanoparticles. It was concluded that these plasmid DNA-coated nanoparticles may have potential for immunization via the nasal route.

Administration, Intranasal↗

PubMed2005

Study on brain targeting of raltitrexed following intranasal administration in rats.

PURPOSE: To investigate the levels of raltitrexed (RTX) in blood and different brain tissues in rats and to find out whether there is any direct drug transport from nasal cavity to brain tissues following intranasal (i.n.) administration. METHODS: Raltitrexed was administered to male Sprague-Dawley rats either intranasally or intravenously. Drug concentrations in blood and brain tissues were determined at different times post dosing. RESULTS: The plasma levels achieved after i.n. administration were significantly lower than those following intravenous (i.v.) administration (P < 0.05) before 120 min; but were significantly higher (P < 0.05) after 120 min. Following i.n. administration, RTX concentrations in different brain tissues were constantly detected for quite a long time and differed significantly from each other, the rank order being C (OB) > C (OT) > C (CR) > C (CL). On the contrary, RTX appeared only at the initial two or three time points in different brain regions after i.v. injection, and the concentrations were similar. AUC values in four brain regions by the nasal route were 54- to 121-fold compared with the i.v. route, the drug targeting index (DTI) values of nasal route were 71-158 for different brain regions, and about 99% of RTX content within 360 min in the brain were transported via the olfactory pathway. CONCLUSIONS: These results showed that antineoplastic RTX could be directly transported into the brain via the olfactory pathway in rats.

Administration, Intranasal↗

PubMed1999

Transfer of some carboxylic acids in the olfactory system following intranasal administration.

The uptake of [14C]benzoic acid, 4-chloro[14C]benzoic acid, [3H]phthalic acid and [14C]salicylic acid in the nasal passages and brain was determined following a unilateral intranasal instillation in mice. An uptake of radioactivity from the nasal mucosa to the ipsilateral olfactory bulb was observed up to 4 h after administration following intranasal instillation of these carboxylic acids whereas the level was low in the contralateral olfactory bulb. Autoradiography of mice given [14C]benzoic acid and [14C]salicylic acid by intranasal instillation showed a preferential localization of radioactivity in the axonal and glomerular layer of the olfactory bulb 1 h after the administration. Four hours after administration the radioactivity was present as a gradient from the axonal layer towards the center of the olfactory bulb. Pretreatment of mice with a compound known to damage the olfactory neuroepithelium resulted in a decreased uptake of [14C]benzoic acid in the olfactory bulb. Thin layer chromatography of supernatants from the ipsilateral olfactory bulbs of mice given [14C]benzoic acid by nasal instillation indicated that the radioactivity in the bulbs represented unchanged compound. These results suggest that there is a transfer of some aromatic carboxylic acids in the olfactory pathways.

Administration, Intranasal↗

PubMed1998

Comparative clinical pharmacokinetics of single doses of sumatriptan following subcutaneous, oral, rectal and intranasal administration.

Sumatriptan, a 5-HT1 receptor agonist active for the acute treatment of migraine, is currently available as subcutaneous injection and oral tablets. Rectal or intranasal formulations may offer advantages over those marketed. This study compared the pharmacokinetics of sumatriptan via all four routes. Usual absorption parameters were described and the rate of absorption was assessed using deconvolution technics. There were no statistical differences between the non-parenteral routes for tmax or Cmax/AUCinfinity. However, Cmax and AUCtmax were statistically greater with the suppository than with the tablet, but there was no difference between intranasal and oral routes. The highest rate of absorption occurred earlier with the intranasal than with the oral route. Relative to the subcutaneous route, the bioavailability for the suppository was greater than for intranasal spray and oral tablet. The amount of sumatriptan excreted in the urine unchanged was similar for all routes. Sumatriptan in this study was well tolerated.

Administration, Intranasal↗

PubMed2001

Coadministration of antigen and particles optimally stimulates the immune response in an intranasal administration model in mice.

Some particulate matter is known to affect human health, yet the mechanism(s) by which it acts is largely unknown. One of the factors that may play a role in the immune- stimulating activity of particles is binding of allergen to particles. This may turn the particles into allergen carriers, resulting in antigen deposition within the altered inflammatory microenvironment created by the particles. We compared the efficacy of simultaneous versus separate administration of antigen and particles during sensitization in an intranasal exposure model in BALB/c mice. Sensitization consisted of three separate doses (10 microg) of TNP-OVA at Days 1, 2, and 3. Two hundred micrograms of carbon black particles (CBP) were administered either 1 day before sensitization (Day 0), 1 day after sensitization (Day 4), or during sensitization. The latter was performed either at Day 1 (200 microg) or at Days 1, 2, and 3 (67 microg/day). At Day 10 a challenge with 10 microg of TNP-OVA was performed, and at Day 15 the immune response was assessed. The total number of cells as well as antibody-forming cells (AFC) in lymph nodes draining the lung (peribronchial lymph nodes [PBLN]) were determined, and immunoglobulin levels in blood were assessed. Cell numbers of PBLN increased significantly in all particle-treated groups compared to controls. The number of TNP-specific IgG1-forming cells in the groups receiving particles during sensitization was significantly higher than control level. Only groups receiving particles during or before sensitization displayed significantly higher IgG1 levels than controls, in contrast to the group receiving particles after sensitization. Only in animals receiving three doses of 67 microg during sensitization did TNP-specific IgE increase significantly compared to controls. IgG2a did not show significant differences compared to controls, indicating that the response is predominantly Th2 mediated. These data indicate that coadministration of particles at all time points of antigen dosing is the most effective way to stimulate an immune response in our model compared to separate particle and antigen dosing. Also, administration shortly before antigen administration was effective in stimulating an immune response, suggesting that time-dependent processes are involved in immune-stimulating activity of particles, supporting the important role of the altered inflammatory microenvironment created by the particles.

Administration, Intranasal↗

PubMed2007

Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia.

Excessive poly(ADP-ribose) polymerase-1 (PARP-1) activation plays a significant role in ischemic brain damage. Increasing evidence has supported the hypothesis that PARP-1 induces cell death by depleting intracellular NAD+. Based on our in vitro finding that NAD+ treatment can abolish PARP-1-mediated cell death, we hypothesized that NAD+ administration may decrease ischemic brain injury. In this study, we used a rat model of transient focal ischemia to test this hypothesis. We observed that intranasal NAD+ delivery significantly increased NAD+ contents in the brains. Intranasal delivery with 10 mg/kg NAD+ at 2 hours after ischemic onset profoundly decreased infarct formation when assessed either at 24 or 72 hours after ischemia. The NAD+ administration also significantly attenuated ischemia-induced neurological deficits. In contrast, intranasal administration with 10 mg/kg nicotinamide did not decrease ischemic brain damage. These results provide the first in vivo evidence that NAD+ metabolism is a new target for treating brain ischemia, and that NAD+ administration may be a novel strategy for decreasing brain damage in cerebral ischemia and possibly other PARP-1-associated neurological diseases.

Administration, Intranasal↗

PubMed1987

Prevention of atrophic rhinitis in piglets by means of intranasal administration of a live non-AR-pathogenic Bordetella bronchiseptica vaccine.

The effect of intranasal vaccination of piglets with live non-AR-pathogenic Bordetella bronchiseptica (BB-) against Atrophic Rhinitis (AR) was investigated in a preliminary investigation and in a field trial. In the preliminary investigation 2-day-old SPF piglets (n = 13) were vaccinated. Three weeks after vaccination, challenges were carried out by means of a spray with an AR-pathogenic B (BB+) or an AR-pathogenic Pasteurella multocida (PM+) broth-culture. Four weeks later the piglets were necropsied and examined for atrophy of the ventral conchae (AVC). In contrast with the non-vaccinated SPF piglets, the vaccinated piglets showed a strong and significant reduction of AVC, after both BB+ and PM+ challenge. In the field trial three groups were formed by drawing lots: ten litters (82 piglets) were vaccinated; ten litters (92 piglets) formed the control group and 11 litters (104 piglets) were treated with a placebo. The litters were spread over two units. In unit 1 AR and PM+ were demonstrated incidentally, in unit 2, however, persistently. BB+ was isolated equally frequently in both units. Clinical and bacteriological examinations were done in piglets of 3, 6 and 8 weeks of age. Necropsy examinations was carried out in 41 piglets of 8 weeks of age, chosen randomly by drawing lots. In spite of a second vaccination at the age of 3 weeks, BB- was not well established; this was possibly caused by maternal BB antibodies. In the control and placebo groups PM+ was isolated earlier and more frequently than BB+. It appeared that AVC was correlated more strongly with PM+ than with BB+ infection in the field trial. The percentage of piglets with Brachygnathia superior (BS) at the age of 8 weeks indicated the AR situation in the herd. Although a significant reduction of AVC was determined in unit 2, it was not sufficient to indicate that this method of intranasal vaccination is useful in the prevention of AR in practice.

Administration, Intranasal↗

PubMed1991

[An increase in brain temperature in rats to the intranasal administration of thyroliberin].

The integral rat brain temperature was measured by radiothermoscope after intranasal instillation of thyroliberin in a dose 400 mkg. The recording increase of temperature lasted during two hours after instillation. This phenomenon is based both on the direct action of thyroliberin and on its capacity to stimulate the induction of other regulatory peptides.

Administration, Intranasal↗

PubMed1990

Intranasal administration of midazolam to a severely burned child.

This report describes the use of intranasally administered midazolam for sedation in a critically ill burned paediatric patient without venous access. Placement of a central venous catheter was successfully carried out following sedation by this method.

Administration, Intranasal↗

PubMed1996

[Intranasal administration of GnRH in the treatment of uterine myomatosis].

Nine patients in which an intranasal GnRH agonist analog (napharelin acetate) was administered with the purpose of decreasing the size of the myomas, were studied. In all a decrement in uterine and myoma size was observed. The FSH levels decreased since the first treated cycle, whereas LH and E2 levels initially increase, but finally decreased. The patients had menstrual bleeding between four and eight weeks after napharelin withdrawal. The mentioned results elicit the effectivity of GnRH agonist analog for leomyomata treatment.

Administration, Intranasal↗

PubMed1992

Intranasal administration of a beta adrenergic amine: an alternative to metered-dose inhalers.

In anesthetized, artificially ventilated guinea pigs, intranasal and intravenous administration of albuterol produced the same maximum degree of protection against bronchoconstriction induced by bilateral electrical stimulation of the cervical vagal nerves. Intranasal albuterol showed a slower onset of action than intravenous albuterol and exhibited equivalent cardiovascular side effects for the same level of bronchoprotection. Accordingly, intranasal albuterol may represent an alternative to metered-dose inhalation for prophylaxis and treatment of bronchoconstriction in humans.

Administration, Inhalation↗

PubMed1990

Mechanism of nasal absorption of drugs. IV: Plasma levels of radioactivity following intranasal administration of [3H]leucine enkephalin.

To study the factors influencing nasal absorption of a model pentapeptide, plasma levels of total radioactivity were determined following the administration of [3H]tyr-leucine enkephalin to rats intravenously, intranasally alone, and intranasally in the presence of puromycin. The major pathway for transport of radioactivity into the blood from the nasal cavity appeared to be hydrolysis of [3H]tyr-leucine enkephalin to [3H]L-tyrosine, followed by absorption of [3H]L-tyrosine. When puromycin was added to the nasal solution in concentrations at which the in vitro hydrolysis of leucine enkephalin was completely inhibited, the appearance of radioactivity in the plasma was slowed, but plasma concentrations of radioactivity eventually reached levels comparable to those observed in the absence of puromycin. In view of the inhibitory effect of puromycin on the hydrolysis of leucine enkephalin, it was assumed that a significant fraction of the [3H]tyr-leucine enkephalin was absorbed intact in the presence of this substance. However, an assay method for intact leucine enkephalin in plasma is needed to confirm these preliminary observations.

Administration, Intranasal↗

PubMed1999

Intranasal administration of a Schistosoma mansoni glutathione S-transferase-cholera toxoid conjugate vaccine evokes antiparasitic and antipathological immunity in mice.

Mucosal administration of Ags linked to cholera toxin B subunit (CTB) can induce both strong mucosal secretory IgA immune responses and peripheral T cell hyporeactivity. In this study, intranasal (i.n. ) administration of CTB-conjugated Schistosoma mansoni 28-kDa GST (CTB-Sm28GST) was found to protect infected animals from schistosomiasis, especially from immunopathological complications associated with chronic inflammation. Worm burden and liver egg counts were reduced in infected animals treated with the CTB-Sm28GST conjugate as compared with mice infected only, or with mice treated with a control (CTB-OVA) conjugate. However, a more striking and consistent effect was that granuloma formations in liver and lungs of mice treated with CTB-Sm28GST were markedly suppressed. Such treatment was associated with reduced systemic delayed-type hypersensitivity and lymphocyte proliferative responses to Sm28GST. Production of IFN-gamma, IL-3, and IL-5 by liver cells was also markedly reduced after i.n. treatment of CTB-Sm28GST, whereas IL-4 production was not impaired. Intranasal treatment of infected mice with CTB-Sm28GST increased IgG1-, IgG2a-, IgA-, and IgE-Ab-forming cell responses in liver in comparison with treatment with CTB-OVA, or free Sm28GST. Most importantly, mucosal treatment with CTB-Sm28GST significantly reduced animal mortality when administered to chronically infected mice. Our results suggest that it may be possible to design a therapeutic vaccine against schistosomiasis that both limits infection and suppresses parasite-induced pathology.

Administration, Intranasal↗

PubMed1975

Immunity following intranasal administration of an inactivated, freeze-dried A/England/42/72 vaccine.

A group of 23 student volunteers were each inoculated intranasally with 400 IU of inactivated, freeze-dried A/England/42/72 vaccine. Only one volunteer showed a four-fold rise in serum HI antibody following immunization, and the mean increase in serum HI antibody (gmt) for all volunteers did not increase two-fold. Thirteen of the volunteers developed detectable levels of nasal wash neutralizing antibody after immunization; local antibody was most commonly found in volunteers who produced a detectable but less than four-fold fise in serum antibody titre, and who produced nasal washings with relatively high concentrations of protein and secretory IgA. Four weeks after immunization, the vaccinees and a matched group of control subjects were inoculated with attenuated A/England/42/72 (MRC-7) virus. Evidence of infection was found in 14 of 23 (61 per cent) of control subjects and in seven of 23 (30 per cent) of immunized volunteers. This result showed a significant protection (P = 0.04) against challenge virus infection for volunteers given intranasal vaccine.

Administration, Intranasal↗

PubMed1993

Stimulation of secretory antibodies against Bordetella pertussis antigens in the lungs of mice after oral or intranasal administration of liposome-incorporated cell-surface antigens.

Lipopolysaccharide (LPS) and outer membrane protein (OMP) preparations of Bordetella pertussis were incorporated into multilamellar liposomes composed of soya bean-derived phospholipids which were then used for oral and intranasal immunization of mice. Specific antibody responses of animals immunized by either route were measured in lung washes. A specific IgA response to LPS was detected after immunization with the OMP-containing liposomes but not with the LPS-containing liposomes, indicating adjuvant activity of the proteins. The OMP-containing liposomes were significantly more effective in inducing immune responses than the OMP preparation alone. Responses were highest when mice were given a booster 30 days after primary immunization. Maximum responses occurred 20 days after the booster but specific antibody was still detected 75 days after the secondary immunization. These results suggest that this liposome antigen delivery system has potential in stimulating secretory antibody responses which may be helpful in protecting against infection from B. pertussis.

Administration, Intranasal↗

PubMed2004

Intranasal administration of xylazine to reduce stress in elk captured by net gun.

Forty free-ranging elk (Cervus elaphus manitobensis) were captured by net gun in Riding Mountain National Park (Manitoba, Canada) during February 2002 and were administered either saline (control) or xylazine by the intranasal route, to evaluate the efficacy and benefit of intranasal xylazine to reduce stress. Elk that received xylazine had higher relaxation scores than control elk, and the onset of sedation occurred quickly, often <1 min. Serum concentrations of cortisol, creatine kinase, and gamma-glutamyltransferase were lower in elk that received xylazine than in control elk. At the conclusion of handling, the intravenous administration of yohimbine quickly abolished the sedative effect of xylazine, which allowed elk to be released without concern of physical injury due to ataxia. The intranasal administration of xylazine can be used to reduce stress in wild animals under situations where they are being handled while physically restrained.

Administration, Intranasal↗

PubMed2004

Recombinant cholera toxin B subunit (rCTB) as a mucosal adjuvant enhances induction of diphtheria and tetanus antitoxin antibodies in mice by intranasal administration with diphtheria-pertussis-tetanus (DPT) combination vaccine.

Recombinant cholera toxin B subunit (rCTB) which is produced by Bacillus brevis carrying pNU212-CTB acts as a mucosal adjuvant capable of enhancing host immune responses specific to unrelated, mucosally co-administered vaccine antigens. When mice were administered intranasally with diphtheria-pertussis-tetanus (DPT) combination vaccine consisting of diphtheria toxoid (DTd), tetanus toxoid (TTd), pertussis toxoid (PTd), and formalin-treated filamentous hemagglutinin (fFHA), the presence of rCTB elevated constantly high values of DTd- and TTd-specific serum ELISA IgG antibody titres, and protective levels of diphtheria and tetanus toxin-neutralizing antibodies but the absence of rCTB did not. Moreover, the addition of rCTB protected all mice against tetanic symptoms and deaths. DPT combination vaccine raised high levels of serum anti-PT IgG antibody titres regardless of rCTB and protected mice from Bordetella pertussis challenge. These results suggest that co-administration of rCTB as an adjuvant is necessary for induction of diphtheria and tetanus antitoxin antibodies on the occasion of intranasal administration of DPT combination vaccine.

Adjuvants, Immunologic↗

PubMed1985

Maintenance of spermatogenesis by intranasal administration of gonadotropin-releasing hormone in patients with hypothalamic hypogonadism.

Pulsatile administration of GnRH is a new, effective therapy for idiopathic hypothalamic hypogonadism. This therapy requires a computerized pump to deliver GnRH intermittently or repetitive single injections each day. In order to simplify this mode of therapy, we first administered hCG to two of three patients to stimulate Leydig cells, and followed this by pulsatile sc administration of GnRH in all three patients. After induction of spermatogenesis, GnRH was administered intranasally, 200 micrograms every 2 h for 8 doses daily. In all patients treated, normal spermatogenesis was maintained by nasal administration of GnRH over a period of 90, 100, and 181 days, respectively. After this period the treatment was arbitrarily discontinued.

Administration, Intranasal↗