Development of a Soluplus budesonide freeze-dried powder for nasal drug delivery.

PubMed

Pozzoli, Michele; Traini, Daniela; Young, Paul M; Sukkar, Maria B; Sonvico, Fabio

2017-09-01

The aim of this work was to develop an amorphous solid dispersions/solutions (ASD) of a poorly soluble drug, budesonide (BUD) with a novel polymer Soluplus ® (BASF, Germany) using a freeze-drying technique, in order to improve dissolution and absorption through the nasal route. The small volume of fluid present in the nasal cavity limits the absorption of a poorly soluble drug. Budesonide is a corticosteroid, practically insoluble and normally administered as a suspension-based nasal spray. The formulation was prepared through freeze-drying of polymer-drug solution. The formulation was assessed for its physicochemical (specific surface area, calorimetric analysis and X-ray powder diffraction), release properties and aerodynamic properties as well as transport in vitro using RPMI 2650 nasal cells, in order to elucidate the efficacy of the Soluplus-BUD formulation. The freeze-dried Soluplus-BUD formulation (LYO) showed a porous structure with a specific surface area of 1.4334 ± 0.0178 m 2 /g. The calorimetric analysis confirmed an interaction between BUD and Soluplus and X-ray powder diffraction the amorphous status of the drug. The freeze-dried formulation (LYO) showed faster release compared to both water-based suspension and dry powder commercial products. Furthermore, a LYO formulation, bulked with calcium carbonate (LYO-Ca), showed suitable aerodynamic characteristics for nasal drug delivery. The permeation across RPMI 2650 nasal cell model was higher compared to a commercial water-based BUD suspension. Soluplus has been shown to be a promising polymer for the formulation of BUD amorphous solid suspension/solution. This opens up opportunities to develop new formulations of poorly soluble drug for nasal delivery.

Nasal-to-CNS drug delivery: where are we now and where are we heading? An industrial perspective.

PubMed

Landis, Margaret S; Boyden, Tracey; Pegg, Simon

2012-02-01

Delivery of drug therapeutics across the blood-brain barrier is a challenging task for pharmaceutical scientists. Nasal-to-CNS drug delivery has shown promising results in preclinical efficacy models and investigatory human clinical trials. The further development of this technology with respect to the establishment of valid, predictable preclinical species models, translatable pharmacokinetic-pharmacodynamic relationships and definition of toxicology impact will help attract additional pharmaceutical investment in this drug-delivery approach. Further discoveries in nasal nanotechnology, targeted delivery devices and diagnostic olfactory imaging will serve to fuel the advancements in this area of drug delivery.

Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice.

PubMed

Cao, Weiping; Kim, Jin Hyang; Reber, Adrian J; Hoelscher, Mary; Belser, Jessica A; Lu, Xiuhua; Katz, Jacqueline M; Gangappa, Shivaprakash; Plante, Martin; Burt, David S; Sambhara, Suryaprakash

2017-06-05

Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model. Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin increased the frequency of lymphoid- as well as local tissue-resident antibody-secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4 T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing. Copyright © 2017. Published by Elsevier Ltd.

Nasal tip plasty: the delivery approach revisited.

PubMed

Xavier, Rui

2013-02-01

The delivery approach, though very appropriate for remodeling the tip of the nose, has been overlooked in recent years and has often been passed over for the open approach. One reason for this is the intercartilaginous incision used for the delivery approach, which may cause scarring at the nasal valve area, leading to postoperative functional obstruction of the nose. The delivery of the alar cartilages is another negative, as this maneuver will disrupt the collagen fibers that attach the upper lateral cartilages to the cephalic margin of the alar cartilages, leading to a weakening of the tip's support. We propose a modification to the traditional delivery approach by using a transcartilaginous instead of an intercartilaginous incision to prevent damage to the valve area. We also suggest taking advantage of the interference to the tip's support caused by the disruption of the collagen fibers of the scroll area. The purpose of this article is to describe this modification of the delivery approach and to emphasize the advantages that this controlled interference to the tip's support may have in selected cases. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Nasal delivery of analgesic ketorolac tromethamine thermo- and ion-sensitive in situ hydrogels.

PubMed

Li, Xin; Du, Lina; Chen, Xu; Ge, Pingju; Wang, Yu; Fu, Yangmu; Sun, Haiyan; Jiang, Qingwei; Jin, Yiguang

2015-07-15

Ketorolac tromethamine (KT) was potent to treat moderate to moderately severe pains. However, KT solutions for nasal delivery lost quickly from the nasal route. Thermo- and ion-sensitive in-situ hydrogels (ISGs) are appropriate for nasal drug delivery because the intranasal temperature maintains ∼37 °C and nasal fluids consist of plentiful cations. In this study, a novel nasal thermo- and ion-sensitive ISG of KT was prepared with thermo-sensitive poloxamer 407 (P407) and ion-sensitive deacetylated gellan gum (DGG). The optimal formulation of the KT ISG consisted of 3% (w/v) DGG and 18% (w/v) P407 and its viscosity was up to 7.63 Pas at 37 °C. Furthermore, penetration enhancers and bacterial inhibitors were added and their fractions in the ISG were optimized based on transmucosal efficiencies and toxicity on toad pili. Sulfobutyl ether-β-cyclodextrin of 2.5% (w/v) and chlorobutanol of 0.5% (w/v) were chosen as the penetration enhancer and the bacterial inhibitor, respectively. The Fick's diffusion and dissolution of KT could drive it continuous release from the dually sensitive ISG according to the in vitro investigation. Two methods, writhing frequencies induced by acetic acid and latency time of tails retracting from hot water, were used to evaluate the pharmacodynamics of the KT ISG on the mouse models. The writhing frequencies significantly decreased and the latency time of tail retracting was obviously prolonged (p<0.05) for the KT ISG compared to the control. The thermo- and ion-sensitive KT ISG had appropriate gelation temperature, sustained drug release, improved intranasal absorption, obvious pharmacodynamic effect, and negligible nasal ciliotoxicity. It is a promising intranasal analgesic formulation. Copyright © 2015. Published by Elsevier B.V.

Drug delivery in overcoming the blood–brain barrier: role of nasal mucosal grafting

PubMed Central

Marianecci, Carlotta; Rinaldi, Federica; Hanieh, Patrizia Nadia; Di Marzio, Luisa; Paolino, Donatella; Carafa, Maria

2017-01-01

The blood–brain barrier (BBB) plays a fundamental role in protecting and maintaining the homeostasis of the brain. For this reason, drug delivery to the brain is much more difficult than that to other compartments of the body. In order to bypass or cross the BBB, many strategies have been developed: invasive techniques, such as temporary disruption of the BBB or direct intraventricular and intracerebral administration of the drug, as well as noninvasive techniques. Preliminary results, reported in the large number of studies on the potential strategies for brain delivery, are encouraging, but it is far too early to draw any conclusion about the actual use of these therapeutic approaches. Among the most recent, but still pioneering, approaches related to the nasal mucosa properties, the permeabilization of the BBB via nasal mucosal engrafting can offer new potential opportunities. It should be emphasized that this surgical procedure is quite invasive, but the implication for patient outcome needs to be compared to the gold standard of direct intracranial injection, and evaluated whilst keeping in mind that central nervous system diseases and lysosomal storage diseases are chronic and severely debilitating and that up to now no therapy seems to be completely successful. PMID:28184152

Needle-free nasal delivery of glucagon for treatment of diabetes-related severe hypoglycemia: toxicology of polypropylene resin used in delivery device.

PubMed

Reno, Frederick E; Edwards, C Nicholas; Bendix Jensen, Morten; Török-Bathó, Magdolna; Esdaile, David J; Piché, Claude; Triest, Myriam; Carballo, Dolorès

2016-09-01

The intranasal route is a promising route of administration for several emergency rescue drugs including naloxone and glucagon. Glucagon nasal powder (GNP) is a novel, needle-free delivery system for intranasal administration of glucagon for the treatment of severe hypoglycemia, an infrequent but serious complication of insulin use in patients with diabetes. The GNP delivery device is a compact, highly portable, single-use nasal powder dosing device constructed of polypropylene that allows for simple, single-step administration. To evaluate the toxicological profile of the polypropylene resin used in the actuator part of the delivery device that will contact skin and nasal mucosal membranes of the patient, we performed an in vitro cytotoxicity study, a skin sensitization study and an irritation (intracutaneous reactivity) study in animal models. Extracts of the actuator of the GNP device were generated from HAM F12 medium with 10% fetal bovine serum, 0.9% sodium chloride (NaCl) or sesame oil. The in vitro cytotoxicity test was performed in cultured L929 mouse fibroblasts. Skin sensitization analysis was performed in 10 guinea pigs according to the Magnusson-Kligman method, using a maximization method with Freund's Complete Adjuvant. Irritation following intracutaneous/intradermal treatment with device extracts (NaCl and sesame oil extractants) was assessed in three New Zealand White rabbits. In vitro cytotoxicity test: Both undiluted and diluted extract showed no toxicity (i.e. no abnormal morphology, cell death or cell lysis) toward L929 fibroblasts (cytotoxicity grade 0). Sensitization test in guinea pigs: Challenge with device extracts did not evoke positive responses in test animals previously induced with device extracts. The net response value represented an incidence rate of 0% and a net dermal irritation score value of 0.00. Irritation (intracutaneous/intradermal) test in New Zealand White rabbits: Device extracts and corresponding vehicle controls caused

In vitro evaluation of radio-labeled aerosol delivery via a variable-flow infant CPAP system.

PubMed

Farney, Kimberly D; Kuehne, Brandon T; Gibson, Laurie A; Nelin, Leif D; Shepherd, Edward G

2014-03-01

Nasal CPAP is widely used in neonatal ICUs. Aerosolized medications such as inhaled steroids and β agonists are commonly administered in-line through nasal CPAP, especially to infants with bronchopulmonary dysplasia. We hypothesized that aerosol delivery to the lungs via variable-flow nasal CPAP in an in vitro model would be unreliable, and that the delivery would depend on the position of the aerosol generator within the nasal CPAP circuit. We used a system that employed a test lung placed in a plastic jar and subjected to negative pressure. Simulated inspiration effort was measured with a heated-wire anemometer. We used technetium-99m-labeled diethylene triamine penta-acetic acid as our aerosol. The nebulizer was placed either close to the humidifier or close to the nasal prongs in the circuit, and patient effort was simulated with a minute ventilation of 0.4 L/min. Relative aerosol delivery to the infant test lung with the nebulizer close to the humidifier was extremely low (0.3 ± 0.4%), whereas placing the nebulizer close to the nasal prongs resulted in significantly (P < .001) improved delivery (21 ± 11%). Major areas of aerosol deposition with the nebulizer close to the humidifier versus close to the nasal prongs were: nebulizer (10 ± 4% vs 33 ± 13%, P < .001), exhalation limb (9 ± 17% vs 26 ± 30%, P = .23), and generator tubing (21 ± 11% vs 19 ± 20%, P = .86). Placing the nebulizer close to the humidifier resulted in 59 ± 8% of the aerosol being deposited in the inhalation tubing along the heater wire. Isotope delivery from an aerosol generator placed near the humidifier on variable-flow nasal CPAP was negligible in this in vitro setup; however, such delivery was significantly improved by locating the aerosol generator closer to the nasal CPAP interface.

Paracellular permeation-enhancing effect of AT1002 C-terminal amidation in nasal delivery

PubMed Central

Song, Keon-Hyoung; Kim, Sang-Bum; Shim, Chang-Koo; Chung, Suk-Jae; Kim, Dae-Duk; Rhee, Sang-Ki; Choi, Guang J; Kim, Chul-Hyun; Kim, Kiyoung

2015-01-01

Background The identification of permeation enhancers has gained interest in the development of drug delivery systems. A six-mer peptide, H-FCIGRL-OH (AT1002), is a tight junction modulator with promising permeation-enhancing activity. AT1002 enhances the transport of molecular weight markers or agents with low bioavailability with no cytotoxicity. However, AT1002 is not stable in neutral pH or after incubation under physiological conditions, which is necessary to fully uncover its permeation-enhancing effect. Thus, we increased the stability or mitigated the instability of AT1002 by modifying its terminal amino acids and evaluated its subsequent biological activity. Methods C-terminal-amidated (FCIGRL-NH2, Pep1) and N-terminal-acetylated (Ac-FCIGRL, Pep2) peptides were analyzed by liquid chromatography–mass spectrometry. We further assessed cytotoxicity on cell monolayers, as well as the permeation-enhancing activity following nasal administration of the paracellular marker mannitol. Results Pep1 was nontoxic to cell monolayers and showed a relatively low decrease in peak area compared to AT1002. In addition, administration of mannitol with Pep1 resulted in significant increases in the area under the plasma concentration–time curve and peak plasma concentration at 3.63-fold and 2.68-fold, respectively, compared to mannitol alone. In contrast, no increase in mannitol concentration was shown with mannitol/AT1002 or mannitol/Pep2 compared to the control. Thus, Pep1 increased the stability or possibly reduced the instability of AT1002, which resulted in an increased permeation-enhancing effect of AT1002. Conclusion These results suggest the potential usefulness of C-terminal-amidated AT1002 in enhancing nasal drug delivery, which may lead to the development of a practical drug delivery technology for drugs with low bioavailability. PMID:25848218

Development of a Transnasal Delivery System for Recombinant Human Growth Hormone (rhGH): Effects of the Concentration and Molecular Weight of Poly-L-arginine on the Nasal Absorption of rhGH in Rats.

PubMed

Kawashima, Ryo; Uchida, Masaki; Yamaki, Tsutomu; Ohtake, Kazuo; Hatanaka, Tomomi; Uchida, Hiroyuki; Ueda, Hideo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

2016-01-01

A novel system for delivering recombinant human growth hormone (rhGH) that is noninvasive and has a simple method of administration is strongly desired to improve the compliance of children. The aim of this study was to investigate the potential for the intranasal (i.n.) co-administration of rhGH with poly-L-arginine (PLA) as a novel delivery system by evaluating the effects of the concentration and molecular weight of PLA on the nasal absorption of rhGH. The influence of the formation of insoluble aggregates and a soluble complex in the dosage formulation on nasal rhGH absorption was also evaluated by size-exclusion chromatography and ultrafiltration. PLA enhanced the nasal absorption of rhGH at each concentration and molecular weight examined. Nasal rhGH absorption increased dramatically when the PLA concentration was 1.0 % (w/v) due to the improved solubility of rhGH in the formulation. A delay in rhGH absorption was observed when the molecular weight of PLA was increased. This appeared to be because the increase in molecular weight caused the formation of a soluble complex. It seems that the PLA concentration affects the absorption-enhancing effect on rhGH, while the molecular weight of PLA affects the time when the maximum plasma rhGH concentration was reached (Tmax) of rhGH after i.n. administration, mainly because of the interactions among rhGH, PLA, and additives. Therefore, the transnasal rhGH delivery system using PLA is considered to be a promising alternative to subcutaneous (s.c.) injection if these interactions are sufficiently controlled.

Noninvasive delivery systems for peptides and proteins in osteoporosis therapy: a retroperspective.

PubMed

Hoyer, Herbert; Perera, Glen; Bernkop-Schnürch, Andreas

2010-01-01

The aim of this review is to provide the reader general and inspiring prospects in various attempts to make noninvasive delivery systems of calcitonin and teriparatide feasible and as convenient as possible. Calcitonin and teriparatide play an important role in both calcium homeostasis and bone remodelling. Currently calcitonin is available as a subcutaneous injection and as a nasal spray whereas teriparatide is administered subcutaneously. In the past few years, an increasing number of articles about drug delivery systems for calcitonin and teriparatide have been published. These delivery systems have been developed to overcome the inherent barriers for the uptake across the diverse membranes on the various routes for protein and peptide delivery. Co-administration of permeation enhancers, mucoadhesive agents, viscosity modifying agents, multifunctional polymers, protease inhibitors as well as encapsulation and chemical modification are utilized in order to improve calcitonin and teriparatide absorption after oral, nasal, pulmonal, or buccal administration. The majority of research groups have been working on the development of formulations based on the encapsulation of molecules in biodegradable and biocompatible polymeric nanoparticles. However these observations are based on data obtained under different experimental conditions. Hence, it is difficult to compare the obtained results in order to draw general conclusions about the most promising characteristics required for oral and nasal formulations for these peptides.

Same Noses, Different Nasalance Scores: Data from Normal Subjects and Cleft Palate Speakers for Three Systems for Nasalance Analysis

ERIC Educational Resources Information Center

Bressmann, Tim; Klaiman, Paula; Fischbach, Simone

2006-01-01

Nasalance scores from the Nasometer, the NasalView and the OroNasal System were compared. The data was collected from 50 normal participants and 19 hypernasal patients with cleft palate. The Nasometer had the lowest nasalance scores for the non-nasal Zoo Passage and that the OroNasal System had the lowest nasalance scores for the Nasal Sentences.…

Impact of airborne particle size, acoustic airflow and breathing pattern on delivery of nebulized antibiotic into the maxillary sinuses using a realistic human nasal replica.

PubMed

Leclerc, Lara; Pourchez, Jérémie; Aubert, Gérald; Leguellec, Sandrine; Vecellio, Laurent; Cottier, Michèle; Durand, Marc

2014-09-01

Improvement of clinical outcome in patients with sinuses disorders involves targeting delivery of nebulized drug into the maxillary sinuses. We investigated the impact of nebulization conditions (with and without 100 Hz acoustic airflow), particle size (9.9 μm, 2.8 μm, 550 nm and 230 nm) and breathing pattern (nasal vs. no nasal breathing) on enhancement of aerosol delivery into the sinuses using a realistic nasal replica developed by our team. After segmentation of the airways by means of high-resolution computed tomography scans, a well-characterized nasal replica was created using a rapid prototyping technology. A total of 168 intrasinus aerosol depositions were performed with changes of aerosol particle size and breathing patterns under different nebulization conditions using gentamicin as a marker. The results demonstrate that the fraction of aerosol deposited in the maxillary sinuses is enhanced by use of submicrometric aerosols, e.g. 8.155 ± 1.476 mg/L of gentamicin in the left maxillary sinus for the 2.8 μm particles vs. 2.056 ± 0.0474 for the 550 nm particles. Utilization of 100-Hz acoustic airflow nebulization also produced a 2- to 3-fold increase in drug deposition in the maxillary sinuses (e.g. 8.155 ± 1.476 vs. 3.990 ± 1.690 for the 2.8 μm particles). Our study clearly shows that optimum deposition was achieved using submicrometric particles and 100-Hz acoustic airflow nebulization with no nasal breathing. It is hoped that our new respiratory nasal replica will greatly facilitate the development of more effective delivery systems in the future.

Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application.

PubMed

Tanaka, Akiko; Furubayashi, Tomoyuki; Arai, Mari; Inoue, Daisuke; Kimura, Shunsuke; Kiriyama, Akiko; Kusamori, Kosuke; Katsumi, Hidemasa; Yutani, Reiko; Sakane, Toshiyasu; Yamamoto, Akira

2018-03-05

Oxytocin (OXT) is a cyclic nonapeptide, two amino acids of which are cysteine, forming an intramolecular disulfide bond. OXT is produced in the hypothalamus and is secreted into the bloodstream from the posterior pituitary. As recent studies have suggested that OXT is a neurotransmitter exhibiting central effects important for social deficits, it has drawn much attention as a drug candidate for the treatment of autism. Although human-stage clinical trials of the nasal spray of OXT for the treatment of autism have already begun, few studies have examined the pharmacokinetics and brain distribution of OXT after nasal application. The aim of this study is to evaluate the disposition, nasal absorption, and therapeutic potential of OXT after nasal administration. The pharmacokinetics of OXT after intravenous bolus injection to rats followed a two-compartment model, with a rapid initial half-life of 3 min. The nasal bioavailability of OXT was approximately 2%. The brain concentration of OXT after nasal application was much higher than that after intravenous application, despite much lower concentrations in the plasma. More than 95% of OXT in the brain was directly transported from the nasal cavity. The in vivo stress-relief effect by OXT was observed only after intranasal administration. These results indicate that pharmacologically active OXT was effectively delivered to the brain after intranasal administration. In conclusion, the nasal cavity is a promising route for the efficient delivery of OXT to the brain.

[Preparation of freeze-dried powder of recombinate hirudin-2 nanoparticle for nasal delivery and permeability through nasal membrane in vitro].

PubMed

Chen, Ming-Xia; Zhang, Jian-Bao; Yu, Ji-Ping; Ye, Jing; Wei, Bao-Hong; Zhang, Yu-Jie

2013-06-01

To optimize the freeze-dried powder preparation technology of recombinate hirudin-2 (rHV2) nanoparticle which has bio-adhesive characteristic for nasal delivery, also to investigate its stability and permeability through nasal membrane in vitro. Taking the appearance, rediffusion of nanoparticle and rHV2 encapsulation efficiency as the evaluation indexes. Cryoprotector, the preparative technique and the effect of illumination and high temperature factors on its stability for rHV2 freeze-dried powder were investigated. Using Fraze diffusion cell technique, the permeability of rHV2 across rabbit nasal mucous membrane in chitosan solution, chitosan nanoparticle, and nanoparticle frozen-dried powder were compared with that in normal saline solution. The optimized preparation of rHV2 nanoparticle freeze-dried powder was as follows: 5% trehalose and glucose (1:1) was used as cryoprotector, nanoparticle solution was freezed for 24 h in vacuum frozen-dryer after being pre-freezed for 24 h. The content of rHV2 in the freeze-dried powder was 1.1 ug/mg. Illumination had little effect on the appearance, rediffusion and encapsulation efficiency of the rHV2 freeze-dried powder. High temperature could obviously influence the appearance of nanoparticle freeze-dried powder. The permeability coefficient (P) of nanoparticle was 5 times more than that in chictonson solution. It was indicated that chitosan nanoparticle has effect on increasing the permeability of rHV2. The freeze-dried powder of chitosan nanoparticle can be a good nasal preparation of rHV2.

Veterinary vaccine nanotechnology: pulmonary and nasal delivery in livestock animals.

PubMed

Calderon-Nieva, Daniella; Goonewardene, Kalhari Bandara; Gomis, Susantha; Foldvari, Marianna

2017-08-01

Veterinary vaccine development has several similarities with human vaccine development to improve the overall health and well-being of species. However, veterinary goals lean more toward feasible large-scale administration methods and low cost to high benefit immunization. Since the respiratory mucosa is easily accessible and most infectious agents begin their infection cycle at the mucosa, immunization through the respiratory route has been a highly attractive vaccine delivery strategy against infectious diseases. Additionally, vaccines administered via the respiratory mucosa could lower costs by removing the need of trained medical personnel, and lowering doses yet achieving similar or increased immune stimulation. The respiratory route often brings challenges in antigen delivery efficiency with enough potency to induce immunity. Nanoparticle (NP) technology has been shown to enhance immune activation by producing higher antibody titers and protection. Although specific mechanisms between NPs and biological membranes are still under investigation, physical parameters such as particle size and shape, as well as biological tissue distribution including mucociliary clearance influence the protection and delivery of antigens to the site of action and uptake by target cells. For respiratory delivery, various biomaterials such as mucoadhesive polymers, lipids, and polysaccharides have shown enhanced antibody production or protection in comparison to antigen alone. This review presents promising NPs administered via the nasal or pulmonary routes for veterinary applications specifically focusing on livestock animals including poultry.

Preparation and brain delivery of nasal solid lipid nanoparticles of quetiapine fumarate in situ gel in rat model of schizophrenia

PubMed Central

Li, Jian-Chun; Zhang, Wen-Jing; Zhu, Jin-Xiu; Zhu, Na; Zhang, Hong-Min; Wang, Xiu; Zhang, Jin; Wang, Qing-Qing

2015-01-01

To investigate the brain delivery in rat by nasal Quetiapine fumarate (QF) loaded with solid lipid nanoparticles in situ gel (QF-SLN-gel). QF-SLN-gel was prepared through micro-emulsion technique. The rat model of schizophrenia was established by intraperitoneal injection of (+)-MK-801, evaluated by stereotypic behavior, Mori’s Water Maze (MWM) test and hematoxylin and eosin (HE) staining of hippocampus. The animals were administrated with QF via oral, nasal or tail vein approach and the concentration of QF in blood and brain was determined using high performance liquid chromatography (HPLC). The QF-SLN-gel was even and transparent, having size of 117.8±2.67 d.nm, potential of 57.2±0.24 mV and EF of 97.6±0.58%. After administration of QF-SLN-gel, the concentration of QF in blood and brain of rats in nasal QF-SLN-gel group was similar with that of rats in tail vein QF group, but significantly higher than that of rats in oral QF group. The hippocampal morphology changes induced by (+)-MK-801 were ameliorated by QF, with advantage of nasal QF-SLN-gel over tail vein QF. The nasal QF-SLN-gel had stable and good brain delivery and could ameliorate the damages in rat model of schizophrenia induced by (+)-MK-801. PMID:26770349

Variability in Nose-to-Lung Aerosol Delivery

PubMed Central

Walenga, Ross L; Tian, Geng; Hindle, Michael; Yelverton, Joshua; Dodson, Kelley; Longest, P. Worth

2014-01-01

Nasal delivery of lung targeted pharmaceutical aerosols is ideal for drugs that need to be administered during high flow nasal cannula (HFNC) gas delivery, but based on previous studies losses and variability through both the delivery system and nasal cavity are expected to be high. The objective of this study was to assess the variability in aerosol delivery through the nose to the lungs with a nasal cannula interface for conventional and excipient enhanced growth (EEG) delivery techniques. A database of nasal cavity computed tomography (CT) scans was collected and analyzed, from which four models were selected to represent a wide range of adult anatomies, quantified based on the nasal surface area-to-volume ratio (SA/V). Computational fluid dynamics (CFD) methods were validated with existing in vitro data and used to predict aerosol delivery through a streamlined nasal cannula and the four nasal models at a steady state flow rate of 30 L/min. Aerosols considered were solid particles for EEG delivery (initial 0.9 μm and 1.5 μm aerodynamic diameters) and conventional droplets (5 μm) for a control case. Use of the EEG approach was found to reduce depositional losses in the nasal cavity by an order of magnitude and substantially reduce variability. Specifically, for aerosol deposition efficiency in the four geometries, the 95% confidence intervals (CI) for 0.9 and 5 μm aerosols were 2.3-3.1 and 15.5-66.3%, respectively. Simulations showed that the use of EEG as opposed to conventional methods improved delivered dose of aerosols through the nasopharynx, expressed as penetration fraction (PF), by approximately a factor of four. Variability of PF, expressed by the coefficient of variation (CV), was reduced by a factor of four with EEG delivery compared with the control case. Penetration fraction correlated well with SA/V for larger aerosols, but smaller aerosols showed some dependence on nasopharyngeal exit hydraulic diameter. In conclusion, results indicated that

Ion-Responsive Drug Delivery Systems.

PubMed

Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro

2018-02-08

Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Preparation and in vitro characterization of thermosensitive and mucoadhesive hydrogels for nasal delivery of phenylephrine hydrochloride.

PubMed

Xu, Xiaofeng; Shen, Yan; Wang, Wei; Sun, Chunmeng; Li, Chang; Xiong, Yerong; Tu, Jiasheng

2014-11-01

The aim of the present work was to develop a nasal delivery system of phenylephrine hydrochloride (PE) in spray form to make prolonged remedy of nasal congestion. The formulations contain the thermosensitive hydrogel, i.e., Poloxamer 407 (P407) and Poloxamer 188 (P188) mixtures, and mucoadhesives, i.e., ε-polylysine (ε-PL) and low molecular weight sodium hyaluronate (MW 11,000Da). The in vitro characterizations of formulations including rheology studies, texture profiles and in vitro mucoadhesion potential were investigated after gelation temperatures measurements. The results showed that the concentration of P407 or P188 had significant influence on gelation temperature and texture profiles. The addition of mucoadhesives, though lowered the gel strength of formulations, increased interaction with mucin. After screening, two formulations (i.e., 1.0% PE/0.5% ε-PL/17% P407/0.5% P188 or Formulation A; and 1.0% PE/0.5% HA/17% P407/0.8% P188 or Formulation B) presenting suitable gelation temperatures (∼32°C) were used for further studies on in vitro release behaviors and mucosa ciliotoxicity. Both formulations showed sustained release of PE for up to 8h and similar toxicity to saline, the negative control. Thus, the thermosensitive and mucoadhesive PE-containing hydrogels are promising to achieve prolonged decongestion in nasal cavity. Copyright © 2014 Elsevier B.V. All rights reserved.

Surface-Modified Nanocarriers for Nose-to-Brain Delivery: From Bioadhesion to Targeting

PubMed Central

Clementino, Adryana; Buttini, Francesca; Colombo, Gaia; Pescina, Silvia; Stanisçuaski Guterres, Silvia; Nicoli, Sara

2018-01-01

In the field of nasal drug delivery, nose-to-brain delivery is among the most fascinating applications, directly targeting the central nervous system, bypassing the blood brain barrier. Its benefits include dose lowering and direct brain distribution of potent drugs, ultimately reducing systemic side effects. Recently, nasal administration of insulin showed promising results in clinical trials for the treatment of Alzheimer’s disease. Nanomedicines could further contribute to making nose-to-brain delivery a reality. While not disregarding the need for devices enabling a formulation deposition in the nose’s upper part, surface modification of nanomedicines appears the key strategy to optimize drug delivery from the nasal cavity to the brain. In this review, nanomedicine delivery based on particle engineering exploiting surface electrostatic charges, mucoadhesive polymers, or chemical moieties targeting the nasal epithelium will be discussed and critically evaluated in relation to nose-to-brain delivery. PMID:29543755

Mannan-decorated thiolated Eudragit microspheres for targeting antigen presenting cells via nasal vaccination.

PubMed

Li, Hui-Shan; Singh, Bijay; Park, Tae-Eun; Hong, Zhong-Shan; Kang, Sang-Kee; Cho, Chong-Su; Choi, Yun-Jaie

2015-12-01

Mucosal vaccination of protein as an antigen requires appropriate delivery or adjuvant systems to deliver antigen to mucosal immune cells efficiently and generate valid immune responses. For successful nasal immunization, the obstacles imposed by the normal process of mucociliary clearance which limits residence time of applied antigens and low antigen delivery to antigen presenting cells (APCs) in nasal associated lymphoid tissue (NALT) need to be overcome for the efficient vaccination. Here, we prepared mucoadhesive and mannan-decorated thiolated Eudragit microspheres (Man-TEM) as a nasal vaccine carrier to overcome the limitations. Mucoadhesive thiolated Eudragit (TE) were decorated with mannan for targeting mannose receptors (MR) in antigen presenting cells (APCs) to obtain efficient immune responses. The potential adjuvant ability of Man-TEM for intranasal immunization was confirmed by in vitro and in vivo experiments. In mechanistic study using APCs in vitro, we obtained that Man-TEM enhanced the receptor-mediated endocytosis by stimulating the MR receptors of APCs. The nasal vaccination of OVA-loaded Man-TEM in mice showed higher levels of serum IgG and mucosal sIgA than the soluble OVA group due to the specific recognition of MR of APCs by the mannan in the Man-TEM. These results suggest that mucoadhesive and Man-TEM may be a promising candidate for nasal vaccine delivery system to elicit systemic and mucosal immunity. Copyright © 2015 Elsevier B.V. All rights reserved.

Targeted delivery of antigen to hamster nasal lymphoid tissue with M-cell-directed lectins.

PubMed Central

Giannasca, P J; Boden, J A; Monath, T P

1997-01-01

The nasal cavity of a rodent is lined by an epithelium organized into distinct regional domains responsible for specific physiological functions. Aggregates of nasal lymphoid tissue (NALT) located at the base of the nasal cavity are believed to be sites of induction of mucosal immune responses to airborne antigens. The epithelium overlying NALT contains M cells which are specialized for the transcytosis of immunogens, as demonstrated in other mucosal tissues. We hypothesized that NALT M cells are characterized by distinct glycoconjugate receptors which influence antigen uptake and immune responses to transcytosed antigens. To identify glycoconjugates that may distinguish NALT M cells from other cells of the respiratory epithelium (RE), we performed lectin histochemistry on sections of the hamster nasal cavity with a panel of lectins. Many classes of glycoconjugates were found on epithelial cells in this region. While most lectins bound to sites on both the RE and M cells, probes capable of recognizing alpha-linked galactose were found to label the follicle-associated epithelium (FAE) almost exclusively. By morphological criteria, the FAE contains >90% M cells. To determine if apical glycoconjugates on M cells were accessible from the nasal cavity, an M-cell-selective lectin and a control lectin in parallel were administered intranasally to hamsters. The M-cell-selective lectin was found to specifically target the FAE, while the control lectin did not. Lectin bound to M cells in vivo was efficiently endocytosed, consistent with the role of M cells in antigen transport. Intranasal immunization with lectin-test antigen conjugates without adjuvant stimulated induction of specific serum immunoglobulin G, whereas antigen alone or admixed with lectin did not. The selective recognition of NALT M cells by a lectin in vivo provides a model for microbial adhesin-host cell receptor interactions on M cells and the targeted delivery of immunogens to NALT following intranasal

Mucoadhesive drug delivery systems

PubMed Central

Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

2011-01-01

Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

Systemic delivery of insulin via the nasal route using a new microemulsion system: In vitro and in vivo studies.

PubMed

Sintov, Amnon C; Levy, Haim V; Botner, Shafir

2010-12-01

The main purpose of this study was to investigate the nasal absorption of insulin from a new microemulsion spray preparation in rabbits. The bioavailability of insulin lispro via the nasal route using a W/O microemulsion was found to reach 21.5% relative to subcutaneous administration, whereas the use of an inverse microemulsion as well as a plain solution yielded less than 1% bioavailability. The profile of plasma glucose levels obtained after nasal spray application of the microemulsion (1IU/kg lispro) was similar to the subcutaneous profile of 0.5IU/kg at the first 90min after application and resulted in a 30-40% drop in glucose levels. The microemulsion system was characterized by DLS, TEM, viscosity measurements, and by construction of pseudo-ternary phase diagram. The average droplet size of an insulin-unloaded and insulin-loaded microemulsions containing 20% aqueous phase (surfactants-to-oil ratio=87:13) was 2nm and 2.26nm in diameter, respectively. In addition, the effect of the microemulsion on FITC-labeled insulin permeation was examined across the porcine nasal mucosa in vitro. The permeability coefficient of FITC-insulin via the microemulsion was 0.210±0.048cm/h with a lag time of 10.9±6.5min, whereas the permeability coefficient from a plain solution was 0.082±0.043cm/h with a lag time of 36.3±10.1min. In view of the absorption differences of insulin between 20%, 50% water-containing microemulsions and an aqueous solution obtained in vitro and in vivo, it has been concluded that the acceleration in the intramucosal transport process is the result of encapsulating insulin within the nano-droplet clusters of a W/O microemulsion, while the microemulsion ingredients seems to have no direct role. Copyright © 2010 Elsevier B.V. All rights reserved.

Novel engineered systems for oral, mucosal and transdermal drug delivery.

PubMed

Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

2013-08-01

Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

Influence of deposition and spray pattern of nasal powders on insulin bioavailability.

PubMed

Pringels, E; Callens, C; Vervaet, C; Dumont, F; Slegers, G; Foreman, P; Remon, J P

2006-03-09

The influence of the deposition pattern and spray characteristics of nasal powder formulations on the insulin bioavailability was investigated in rabbits. The formulations were prepared by freeze drying a dispersion containing a physical mixture of drum dried waxy maize starch (DDWM)/Carbopol 974P (90/10, w/w) or a spray-dried mixture of Amioca starch/Carbopol 974P (25/75, w/w). The deposition in the nasal cavity of rabbits and in a silicone human nose model after actuation of three nasal delivery devices (Monopowder, Pfeiffer and experimental system) was compared and related to the insulin bioavailability. Posterior deposition of the powder formulation in the nasal cavity lowered the insulin bioavailability. To study the spray pattern, the shape and cross-section of the emitted powder cloud were analysed. It was concluded that the powder bulk density of the formulation influenced the spray pattern. Consequently, powders of different bulk density were prepared by changing the solid fraction of the freeze dried dispersion and by changing the freezing rate during freeze drying. After nasal delivery of these powder formulations no influence of the powder bulk density and of the spray pattern on the insulin bioavailability was observed.

Characterization of deposition from nasal spray devices using a computational fluid dynamics model of the human nasal passages.

PubMed

Kimbell, Julia S; Segal, Rebecca A; Asgharian, Bahman; Wong, Brian A; Schroeter, Jeffry D; Southall, Jeremy P; Dickens, Colin J; Brace, Geoff; Miller, Frederick J

2007-01-01

Many studies suggest limited effectiveness of spray devices for nasal drug delivery due primarily to high deposition and clearance at the front of the nose. Here, nasal spray behavior was studied using experimental measurements and a computational fluid dynamics model of the human nasal passages constructed from magnetic resonance imaging scans of a healthy adult male. Eighteen commercially available nasal sprays were analyzed for spray characteristics using laser diffraction, high-speed video, and high-speed spark photography. Steadystate, inspiratory airflow (15 L/min) and particle transport were simulated under measured spray conditions. Simulated deposition efficiency and spray behavior were consistent with previous experimental studies, two of which used nasal replica molds based on this nasal geometry. Deposition fractions (numbers of deposited particles divided by the number released) of 20- and 50-microm particles exceeded 90% in the anterior part of the nose for most simulated conditions. Predicted particle penetration past the nasal valve improved when (1) the smaller of two particle sizes or the lower of two spray velocities was used, (2) the simulated nozzle was positioned 1.0 rather than 0.5 or 1.5 cm into the nostril, and (3) inspiratory airflow was present rather than absent. Simulations also predicted that delaying the appearance of normal inspiratory airflow more than 1 sec after the release of particles produced results equivalent to cases in which no inspiratory airflow was present. These predictions contribute to more effective design of drug delivery devices through a better understanding of the effects of nasal airflow and spray characteristics on particle transport in the nose.

Regional deposition of nasal sprays in adults: A wide ranging computational study.

PubMed

Kiaee, Milad; Wachtel, Herbert; Noga, Michelle L; Martin, Andrew R; Finlay, Warren H

2018-05-01

The present work examines regional deposition within the nose for nasal sprays over a large and wide ranging parameter space by using numerical simulation. A set of 7 realistic adult nasal airway geometries was defined based on computed tomography images. Deposition in 6 regions of each nasal airway geometry (the vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and nasopharynx) was determined for varying particle diameter, spray cone angle, spray release direction, particle injection speed, and particle injection location. Penetration of nasal spray particles through the airway geometries represented unintended lung exposure. Penetration was found to be relatively insensitive to injection velocity, but highly sensitive to particle size. Penetration remained at or above 30% for particles exceeding 10 μm in diameter for several airway geometries studied. Deposition in the turbinates, viewed as desirable for both local and systemic nasal drug delivery, was on average maximized for particles ranging from ~20 to 30 μm in diameter, and for low to zero injection velocity. Similar values of particle diameter and injection velocity were found to maximize deposition in the olfactory region, a potential target for nose-to-brain drug delivery. However, olfactory deposition was highly variable between airway geometries, with maximum olfactory deposition ranging over 2 orders of magnitude between geometries. This variability is an obstacle to overcome if consistent dosing between subjects is to be achieved for nose-to-brain drug delivery. Copyright © 2018 John Wiley & Sons, Ltd.

Aerosol Delivery with Two Nebulizers Through High-Flow Nasal Cannula: A Randomized Cross-Over Single-Photon Emission Computed Tomography-Computed Tomography Study.

PubMed

Dugernier, Jonathan; Hesse, Michel; Jumetz, Thibaud; Bialais, Emilie; Roeseler, Jean; Depoortere, Virginie; Michotte, Jean-Bernard; Wittebole, Xavier; Ehrmann, Stephan; Laterre, Pierre-François; Jamar, François; Reychler, Gregory

2017-10-01

High-flow nasal cannula use is developing in ICUs. The aim of this study was to compare aerosol efficiency by using two nebulizers through a high-flow nasal cannula: the most commonly used jet nebulizer (JN) and a more efficient vibrating-mesh nebulizer (VN). Aerosol delivery of diethylenetriaminepentaacetic acid labeled with technetium-99m (4 mCi/4 mL) to the lungs by using a VN (Aerogen Solo ® ; Aerogen Ltd., Galway, Ireland) and a constant-output JN (Opti-Mist Plus Nebulizer ® ; ConvaTec, Bridgewater, NJ) through a high-flow nasal cannula (Optiflow ® ; Fisher & Paykel, New Zealand) was compared in six healthy subjects. Flow rate was set at 30 L/min through the heated humidified circuit. Pulmonary and extrapulmonary deposition was measured by single-photon emission computed tomography combined with a low-dose computed tomographic scan and by planar scintigraphy. Lung deposition was only 3.6 (2.1-4.4) and 1 (0.7-2)% of the nominal dose with the VN and the JN, respectively (p < 0.05). The JN showed higher retained doses than the VN. However, both nebulizers were associated with substantial deposition in the single limb circuit, the humidification chamber, and the nasal cannula [58.2 (51.6-61.6)% of the nominal dose with the VN versus 19.2 (15.8-22.9)% of the nominal dose with the JN, p < 0.05] and in the upper respiratory tract [17.6 (13.4-27.9)% of the nominal dose with the VN and 8.6 (6.0-11.0)% of the nominal dose with the JN, p < 0.05], especially in the nasal cavity. In the specific conditions of the study, pulmonary drug delivery through the high-flow nasal cannula is about 1%-4% of the initial amount of drugs placed in the nebulizer, despite the higher efficiency of the VN as compared with the JN.

Fabrication, Characterization, In vitro Evaluation of Solid Lipid Nanoemulsion of Flunarizine dihydrochloride for Nasal Delivery.

PubMed

Newton, Maria J; Harjot, Kaur

2017-01-01

Flunarizine dihydrochloride (FHC) is used for the prophylaxis to migraine. Flunarizine has solubility problems which is practically insoluble in water and alcohol. Nanoemulsion is the approach to increase the solubility of the insoluble drugs. Nanoemulsions of FHC was prepared which can be given through the alternate route such as nasal drug delivery for migraine. In this research work the solubility of the poorly soluble FHC was successfully improved by preparing it as a nano emulsion. Nanoemulsions can pass through the biological membrane easily so it can be delivered through nasal mucosa by which it may provide a quicker onset of action. The currently available dosage forms are in the form of tablet. The formulations were prepared by using Glycerl Monostearate (GMS), Tween 80 as surfactant and PEG 400: Ethanol as co-surfactant in the distilled water. Nanoemulsions were prepared by step by step procedure. The prepared nanoemulsions were analyzed preliminarily by Master Sizer followed by Zeta Sizer by using the technique Dynamic Photon Correlation Spectroscopy. The best nanoemulsion was subjected to Zeta Potential study. The TEM analysis was carried out on the best formulation to gain the detailed information about the formulation. The best formulation was selected based on the physical appearance, homogenecity of the preparation, Preliminary Master Sizer analysis report, Secondary Zeta Sizer analysis report with Zeta Potential and TEM. The best formulation demonstrated the size in nano range with improved solubility. The FHC nano emulsion was prepared successfully which improved the solubility of the drug. The drug release study on simulated nasal fluid revealed that the preparation is suitable to be delivered through the nasal route. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of Computer System and Vowel Loading on Measures of Nasalance

ERIC Educational Resources Information Center

Awan, Shaheen N.; Omlor, Kristin; Watts, Christopher R.

2011-01-01

Purpose: The purpose of this study was to determine similarities and differences in nasalance scores observed with different computerized nasalance systems in the context of vowel-loaded sentences. Methodology: Subjects were 46 Caucasian adults with no perceived hyper-or hyponasality. Nasalance scores were obtained using the Nasometer 6200 (Kay…

Supplemental oxygen: ensuring its safe delivery during facial surgery.

PubMed

Reyes, R J; Smith, A A; Mascaro, J R; Windle, B H

1995-04-01

Electrosurgical coagulation in the presence of blow-by oxygen is a potential source of fire in facial surgery. A case report of a patient sustaining partial-thickness facial burns secondary to such a flash fire is presented. A fiberglass facial model is then used to study the variables involved in providing supplemental oxygen when an electrosurgical unit is employed. Oxygen flow, oxygen delivery systems, distance from the oxygen source, and coagulation current levels were varied. A nasal cannula and an adapted suction tubing provided the oxygen delivery systems on the model. Both the "displaced" nasal cannula and the adapted suction tubing ignited at a minimum coagulation level of 30 W, an oxygen flow of 2 liters/minute, and a linear distance of 5 cm from the oxygen source. The properly placed nasal cannula did not ignite at any combination of oxygen flow, coagulation current level, or distance from the oxygen source. Facial cutaneous surgery in patients provided supplemental oxygen should be practiced with caution when an electrosurgical unit is used for coagulation. The oxygen delivery systems adapted for use are hazardous and should not be used until their safety has been demonstrated.

Rationally designed nanocarriers for intranasaltherapy of allergic rhinitis: influence of carrier type on in vivo nasal deposition

PubMed Central

Sallam, Marwa Ahmed; Helal, Hala Mahmoud; Mortada, Sana Mohamed

2016-01-01

The aim of this study is to develop a locally acting nasal delivery system of triamcinolone acetonide (TA) for the maintenance therapy of allergic rhinitis. The effect of encapsulating TA in different nanocarriers on its mucosal permeation and retention as well as in vivo nasal deposition has been studied. A comparative study was established between polymeric oil core nanocapsules (NCs), lipid nanocarriers such as nanoemulsion (NE), and nanostructured lipid carriers (NLCs). The elaborated nanocarriers were compared with TA suspension and the commercially available suspension “Nasacort®”. The study revealed that NC provided the highest mucosal retention, as 46.14%±0.048% of the TA initial dose was retained after 24 hours, while showing the least permeation through the nasal mucosa. On the other hand, for TA suspension and Nasacort®, the mucosal retention did not exceed 23.5%±0.047% of the initial dose after 24 hours. For NE and NLC, values of mucosal retention were 19.4%±0.041% and 10.97%±0.13%, respectively. NC also showed lower mucosal irritation and superior stability compared with NE. The in vivo nasal deposition study demonstrated that NC maintained drug in its site of action (nasal cavity mucosa) for the longest period of time. The elaborated polymeric oil core NCs are efficient carriers for the administration of nasally acting TA as it produced the least permeation results, thus decreasing systemic absorption of TA. Although NCs have been administered via various routes, this is the first study to implement the polymeric oil core NC as an efficient carrier for localized nasal drug delivery. PMID:27307734

Response of Preterm Infants to 2 Noninvasive Ventilatory Support Systems: Nasal CPAP and Nasal Intermittent Positive-Pressure Ventilation.

PubMed

Silveira, Carmen Salum Thomé; Leonardi, Kamila Maia; Melo, Ana Paula Carvalho Freire; Zaia, José Eduardo; Brunherotti, Marisa Afonso Andrade

2015-12-01

Noninvasive ventilation (NIV) in preterm infants is currently applied using intermittent positive pressure (2 positive-pressure levels) or in a conventional manner (one pressure level). However, there are no studies in the literature comparing the chances of failure of these NIV methods. The aim of this study was to evaluate the occurrence of failure of 2 noninvasive ventilatory support systems in preterm neonates over a period of 48 h. A randomized, prospective, clinical study was conducted on 80 newborns (gestational age < 37 weeks, birthweight < 2,500 g). The infants were randomized into 2 groups: 40 infants were treated with nasal CPAP and 40 infants with nasal intermittent positive-pressure ventilation (NIPPV). The occurrence of apnea, progression of respiratory distress, nose bleeding, and agitation was defined as ventilation failure. The need for intubation and re-intubation after failure was also observed. There were no significant differences in birth characteristics between groups. Ventilatory support failure was observed in 25 (62.5%) newborns treated with nasal CPAP and in 12 (30%) newborns treated with NIPPV, indicating an association between NIV failure and the absence of intermittent positive pressure (odds ratio [OR] 1.22, P < .05). Apnea (32.5%) was the main reason for nasal CPAP failure. After failure, 25% (OR 0.33) of the newborns receiving nasal CPAP and 12.5% (OR 0.14) receiving NIPPV required invasive mechanical ventilation. Ventilatory support failure was significantly more frequent when nasal CPAP was used. Copyright © 2015 by Daedalus Enterprises.

An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems.

PubMed

Jug, Mario; Hafner, Anita; Lovrić, Jasmina; Kregar, Maja Lusina; Pepić, Ivan; Vanić, Željka; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena

2018-01-05

In vitro dissolution/release tests are an important tool in the drug product development phase as well as in its quality control and the regulatory approval process. Mucosal drug delivery systems are aimed to provide both local and systemic drug action via mucosal surfaces of the body and exhibit significant differences in formulation design, as well as in their physicochemical and release characteristics. Therefore it is not possible to devise a single test system which would be suitable for release testing of such complex dosage forms. This article is aimed to provide a comprehensive review of both compendial and noncompendial methods used for in vitro dissolution/release testing of novel mucosal drug delivery systems aimed for ocular, nasal, oromucosal, vaginal and rectal administration. Copyright © 2017 Elsevier B.V. All rights reserved.

Thiolated polycarbophil as an adjuvant for permeation enhancement in nasal delivery of antisense oligonucleotides.

PubMed

Vetter, A; Martien, R; Bernkop-Schnürch, A

2010-03-01

The purpose of this study was to investigate the effect of thiolated polycarbophil as an adjuvant to enhance the permeation and improve the stability of a phosphorothioate antisense oligonucleotide (PTO-ODN) on the nasal mucosa. Polycarbophil-cysteine (PCP-Cys) was synthesized by the covalent attachment of L-cysteine to the polymeric backbone. Cytotoxicity tests were examined on human nasal epithelial cells from surgery of nasal polyps confirmed by histological studies. Deoxyribonuclease I activity in respiratory region of the porcine nasal cavity was analyzed by an enzymatic assay. The enzymatic degradation of PTO-ODNs on freshly excised porcine nasal mucosa was analyzed and protection of PCP-cysteine toward DNase I degradation was evaluated. Permeation studies were performed in Ussing-type diffusion chambers. PCP-Cys/GSH did not arise a remarkable mortal effect. Porcine respiratory mucosa was shown to possess nuclease activity corresponding to 0.69 Kunitz units/mL. PTO-ODNs were degraded by incubation with nasal mucosa. In the presence of 0.45% thiolated polycarbophil and 0.5% glutathione (GSH), this degradation process could be lowered. In the presence of thiolated polycarbophil and GSH the uptake of PTO-ODNs from the nasal mucosa was 1.7-fold improved. According to these results thiolated polycarbophil/GSH might be a promising excipient for nasal administration of PTO-ODNs. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Nasal Septal Deviations: A Systematic Review of Classification Systems.

PubMed

Teixeira, Jeffrey; Certal, Victor; Chang, Edward T; Camacho, Macario

2016-01-01

Objective. To systematically review the international literature for internal nasal septal deviation classification systems and summarize them for clinical and research purposes. Data Sources. Four databases (including PubMed/MEDLINE) were systematically searched through December 16, 2015. Methods. Systematic review, adhering to PRISMA. Results. After removal of duplicates, this study screened 952 articles for relevance. A final comprehensive review of 50 articles identified that 15 of these articles met the eligibility criteria. The classification systems defined in these articles included C-shaped, S-shaped, reverse C-shaped, and reverse S-shaped descriptions of the septal deviation in both the cephalocaudal and anteroposterior dimensions. Additional studies reported use of computed tomography and categorized deviation based on predefined locations. Three studies graded the severity of septal deviations based on the amount of deflection. The systems defined in the literature also included an evaluation of nasal septal spurs and perforations. Conclusion. This systematic review ascertained that the majority of the currently published classification systems for internal nasal septal deviations can be summarized by C-shaped or reverse C-shaped, as well as S-shaped or reverse S-shaped deviations in the anteroposterior and cephalocaudal dimensions. For imaging studies, predefined points have been defined along the septum. Common terminology can facilitate future research.

Intranasal delivery of ciprofloxacin to rats: A topical approach using a thermoreversible in situ gel.

PubMed

Sousa, Joana; Alves, Gilberto; Oliveira, Paula; Fortuna, Ana; Falcão, Amílcar

2017-01-15

Intranasal administration of antibiotics is an alternative and attractive delivery approach in the treatment of local infections such as chronic rhinosinusitis. This topical route has the advantage of delivering high drug concentrations directly to the site of infection when trying to eradicate the highly resistant bacterial biofilms. The purpose of this study was to assess and compare the pharmacokinetic parameters of ciprofloxacin following intranasal and intravenous administrations to rats in plasma, olfactory bulb and nasal mucosa of two different nasal regions. For intranasal administration a thermoreversible in situ gel was used to increase drug residence time in nasal cavity. Ciprofloxacin concentration time-profile in nasal mucosa of the studied anterior region (at naso- and maxilloturbinates level) was markedly higher after intranasal administration (0.24mg/kg) than that following intravenous administration (10mg/kg), while in nasal mucosa of the more posterior region (at ethmoidal turbinates level) ciprofloxacin concentrations were found to be higher after intranasal administration when the different dose administered by both routes is taken into account. A plateau in ciprofloxacin concentration was observed in nasal mucosa of both studied regions after intranasal administration, suggesting a slow delivery of the drug over a period of time using the nasal gel formulation. In plasma and olfactory bulb, concentration of ciprofloxacin was residual after intranasal administration, which demonstrates this is a safe administration route by preventing systemic and particularly central nervous system adverse effects. Dose-normalized pharmacokinetic parameters of ciprofloxacin exposure to nasal mucosa revealed higher values after intranasal delivery not only in the anterior region but also in the posterior nasal region. In conclusion, topical intranasal administration appears to be advantageous for delivering ciprofloxacin to the biophase, with negligible systemic

Porous nanoparticles as delivery system of complex antigens for an effective vaccine against acute and chronic Toxoplasma gondii infection.

PubMed

Dimier-Poisson, Isabelle; Carpentier, Rodolphe; N'Guyen, Thi Thanh Loi; Dahmani, Fatima; Ducournau, Céline; Betbeder, Didier

2015-05-01

Development of sub-unit mucosal vaccines requires the use of specific delivery systems or immune-modulators such as adjuvants to improve antigen immunogenicity. Nasal route for vaccine delivery by nanoparticles has attracted much interest but mechanisms triggering effective mucosal and systemic immune response are still poorly understood. Here we study the loading of porous nanoparticles (DGNP) with a total extract of Toxoplasma gondii antigens (TE), the delivery of TE by DGNP into airway epithelial, macrophage and dendritic cells, and the subsequent cellular activation. In vitro, DGNP are able to load complex antigens in a stable and quantitative manner. The outstanding amount of antigen association by DGNP is used to deliver TE in airway mucosa cells to induce a cellular maturation with an increased secretion of pro-inflammatory cytokines. Evaluation of nasal vaccine efficiency is performed in vivo on acute and chronic toxoplasmosis mouse models. A specific Th1/Th17 response is observed in vivo after vaccination with DGNP/TE. This is associated with high protection against toxoplasmosis regarding survival and parasite burden, correlated with an increased delivery of antigens by DGNP in airway mucosa cells. This study provides evidence of the potential of DGNP for the development of new vaccines against a range of pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nasal Harmony in Aguaruna.

ERIC Educational Resources Information Center

Moon, Gui-Sun

A discussion of the nasal harmony of Aguaruna, a language of the Jivaroan family in South America, approaches the subject from the viewpoint of generative phonology. This theory of phonology proposes an underlying nasal consonant, later deleted, that accounts for vowel nasalization. Complex rules that suppose a complex system of vowel and…

Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein.

PubMed

Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R

2012-04-02

This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal routes showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.

Systems and Components Fuel Delivery System, Water Delivery System, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

Enhanced Analgesic Responses After Preferential Delivery of Morphine and Fentanyl to the Olfactory Epithelium in Rats

PubMed Central

Hoekman, John D.; Ho, Rodney J.Y.

2011-01-01

Background Centrally acting opioid analgesics such as morphine and fentanyl are effective, but their efficacy is often limited by a delayed response or side effects resulting from systemic first-pass before reaching the brain and the central nervous system (CNS). It is generally accepted that drugs applied to the nasal cavity can directly access the brain and the CNS, which could provide therapeutic advantages such as rapid onset and lower systemic exposure. The olfactory region of the nasal cavity has been implicated in facilitating this direct nose-to-CNS transfer. If the fraction of opioid administered to the olfactory region could be improved, there could be a larger fraction of drug directly delivered to the CNS, mediating greater therapeutic benefit. Methods We have developed a pressurized olfactory delivery (POD) device to consistently and non-invasively deposit a majority of drug on the olfactory region of the nasal cavity in Sprague-Dawley rats. Using the tail-flick latency test and analysis of plasma and CNS tissue drug exposure, we compared distribution and efficacy of the opioids morphine and fentanyl administered to the nasal olfactory region with the POD device or the nasal respiratory region with nose drops or systemically via intraperitoneal (IP) injection. Results Compared to nose drop, POD administration of morphine resulted in significantly higher overall therapeutic effect (AUCeffect) without a significant increase in plasma drug exposure (AUCplasma). POD delivery of morphine resulted in a nose-to-CNS direct transport percentage of 38–55%. POD delivery of fentanyl led to a faster (5 min vs. 10 min) and more intense analgesic effect compared to nasal respiratory administration. Unlike IP injection or nose drop administration, both morphine and fentanyl given by the POD device to olfactory nasal epithelium exhibited clockwise [plasma] versus effect hysteresis after nasal POD administration, consistent with direct nose-to-CNS drug transport

Intranasal delivery of antiviral siRNA.

PubMed

Barik, Sailen

2011-01-01

Intranasal administration of synthetic siRNA is an effective modality of RNAi delivery for the prevention and therapy of respiratory diseases, including pulmonary infections. Vehicles used for nasal siRNA delivery include established as well as novel reagents, many of which have been recently optimized. In general, they all promote significant uptake of siRNA into the lower respiratory tract, including the lung. When properly designed and optimized, these siRNAs offer significant protection against respiratory viruses such as influenza virus, parainfluenza virus and respiratory syncytial virus (RSV). Nasally administered siRNA remains within the lung and does not access systemic blood flow, as judged by its absence in other major organs such as liver, heart, kidney, and skeletal muscle. Adverse immune reaction is generally not encountered, especially when immunogenic and/or off-target siRNA sequences and toxic vehicles are avoided. In fact, siRNA against RSV has entered Phase II clinical trials in human with promising results. Here, we provide a standardized procedure for using the nose as a specific route for siRNA delivery into the lung of laboratory animals. It should be clear that this simple and efficient system has enormous potential for therapeutics.

[Dexpanthenol nasal spray in comparison to dexpanthenol nasal ointment. A prospective, randomised, open, cross-over study to compare nasal mucociliary clearance].

PubMed

Verse, T; Klöcker, N; Riedel, F; Pirsig, W; Scheithauer, M O

2004-07-01

Recent technical developments in metered pump systems allow the production and use of preservative-free nasal products. The aim of the current study is to compare the tolerability of a preservative-free dexpanthenol (5%) nasal spray with that of the established dexpanthenol (5%) nasal ointment, also without preservatives. The main outcome measure was in vivo mucociliary clearance. Mucociliary clearance was assessed by saccharin migration time in 20 volunteers. Wash-out phases were 7 days and the spray or ointment was always applied 20 min before the saccharin test. The study was designed to test for non-inferiority. Saccharin migration time was slightly longer after ointment administration, however, these were not significantly different to nasal spray. The saccharin migration time showed a significant correlation with the age of the volunteers. The upper confidence limit of dexpanthenol nasal spray was markedly less than that of the ointment. Therefore, dexpanthenol nasal spray is at least equal to if not better than dexpanthenol nasal ointment. Due to its ease of administration, preservative-free dexpanthenol nasal spray offers a valuable therapeutic alternative.

Recent advances in protein and Peptide drug delivery: a special emphasis on polymeric nanoparticles.

PubMed

Patel, Ashaben; Patel, Mitesh; Yang, Xiaoyan; Mitra, Ashim K

2014-01-01

Proteins and peptides are widely indicated in many diseased states. Parenteral route is the most commonly em- ployed method of administration for therapeutic proteins and peptides. However, requirement of frequent injections due to short in vivo half-life results in poor patient compliance. Non-invasive drug delivery routes such as nasal, transdermal, pulmonary, and oral offer several advantages over parenteral administration. Intrinsic physicochemical properties and low permeability across biological membrane limit protein delivery via non-invasive routes. One of the strategies to improve protein and peptide absorption is by delivering through nanostructured delivery carriers. Among nanocarriers, polymeric nanoparticles (NPs) have demonstrated significant advantages over other delivery systems. This article summarizes the application of polymeric NPs for protein and peptide drug delivery following oral, nasal, pulmonary, parenteral, transder mal, and ocular administrations.

Recent Advances in Protein and Peptide Drug Delivery: A Special Emphasis on Polymeric Nanoparticles

PubMed Central

Patel, Ashaben; Patel, Mitesh; Yang, Xiaoyan; Mitra, Ashim K.

2015-01-01

Proteins and peptides are widely indicated in many diseased states. Parenteral route is the most commonly employed method of administration for therapeutic proteins and peptides. However, requirement of frequent injections due to short in vivo half-life results in poor patient compliance. Non-invasive drug delivery routes such as nasal, transdermal, pulmonary, and oral offer several advantages over parenteral administration. Intrinsic physicochemical properties and low permeability across biological membrane limit protein delivery via non-invasive routes. One of the strategies to improve protein and peptide absorption is by delivering through nanostructured delivery carriers. Among nanocarriers, polymeric nanoparticles (NPs) have demonstrated significant advantages over other delivery systems. This article summarizes the application of polymeric NPs for protein and peptide drug delivery following oral, nasal, pulmonary, parenteral, transdermal, and ocular administrations. PMID:25106908

Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines

NASA Astrophysics Data System (ADS)

Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-Ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

2010-07-01

Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (`nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

Expanding Alternative Delivery Systems.

ERIC Educational Resources Information Center

Baltzer, Jan A.

Alternative educational delivery systems that might be useful to community colleges are considered. The following categories of delivery systems are covered: broadcast delivery systems; copy delivery systems, print delivery systems, computer delivery systems, telephone delivery systems, and satellites. Among the applications for broadcast…

Computed Intranasal Spray Penetration: Comparisons Before and After Nasal Surgery

PubMed Central

Frank, Dennis O.; Kimbell, Julia S.; Cannon, Daniel; Rhee, John S.

2012-01-01

Background Quantitative methods for comparing intranasal drug delivery efficiencies pre- and postoperatively have not been fully utilized. The objective of this study is to use computational fluid dynamics techniques to evaluate aqueous nasal spray penetration efficiencies before and after surgical correction of intranasal anatomic deformities. Methods Ten three-dimensional models of the nasal cavities were created from pre- and postoperative computed tomography scans in five subjects. Spray simulations were conducted using a particle size distribution ranging from 10–110μm, a spray speed of 3m/s, plume angle of 68°, and with steady state, resting inspiratory airflow present. Two different nozzle positions were compared. Statistical analysis was conducted using Student T-test for matched pairs. Results On the obstructed side, posterior particle deposition after surgery increased by 118% and was statistically significant (p-value=0.036), while anterior particle deposition decreased by 13% and was also statistically significant (p-value=0.020). The fraction of particles that by-passed the airways either pre- or post-operatively was less than 5%. Posterior particle deposition differences between obstructed and contralateral sides of the airways were 113% and 30% for pre- and post-surgery, respectively. Results showed that nozzle positions can influence spray delivery. Conclusions Simulations predicted that surgical correction of nasal anatomic deformities can improve spray penetration to areas where medications can have greater effect. Particle deposition patterns between both sides of the airways are more evenly distributed after surgery. These findings suggest that correcting anatomic deformities may improve intranasal medication delivery. For enhanced particle penetration, patients with nasal deformities may explore different nozzle positions. PMID:22927179

A Review of the Safety, Efficacy and Mechanisms of Delivery of Nasal Oxytocin in Children: Therapeutic Potential for Autism and Prader-Willi Syndrome, and Recommendations for Future Research.

PubMed

DeMayo, Marilena M; Song, Yun Ju C; Hickie, Ian B; Guastella, Adam J

2017-10-01

In this article, we conduct a comprehensive review of existing evidence for the safety and therapeutic potential of intranasal oxytocin in pediatric populations. Unique considerations for dosing and delivery of oxytocin to the nasal passageway in pediatric populations and methods to promote adherence are reviewed. Intranasal oxytocin has been administered to 261 children in three open-label studies and eight randomized controlled trials. To date, the only published results in pediatric populations have focused on autism spectrum disorder (ASD) and Prader-Willi syndrome (PWS). Results regarding efficacy for improving social impairment in ASD are equivocal, partially due to mixed methodological designs, dosing regimens, and outcome measures. At present, there is no randomized controlled evidence that oxytocin provides benefit to individuals with PWS. There is no clear evidence of a link between oxytocin administration and any specific adverse event. Adverse events have been assessed using medical interviews, open reports, checklists, and physiological assessments. Adverse events reports have been largely classified as mild (n = 93), with few moderate (n = 9) or severe (n = 3) events reported. There were 35 additional adverse events reported, without severity ratings. Severe events, hyperactivity and irritability, occurred at first administration in both placebo and oxytocin groups, and subsided subsequent to discontinuation. We note that adverse event monitoring is inconsistent and often lacking, and reporting of its relationship to the study drug is poor. Only one study reported adherence data to suggest high adherence. Recommendations are then provided for the delivery of nasal sprays to the nasal passageway, monitoring, and reporting of efficacy, safety, and adherence for oxytocin nasal spray trials in pediatric populations.

Nasal deposition and clearance in man: comparison of a bidirectional powder device and a traditional liquid spray pump.

PubMed

Djupesland, Per Gisle; Skretting, Arne

2012-10-01

Delivery of powder formulations to the nose is an attractive alternative for many drugs and vaccines. This study compared the regional nasal deposition and clearance patterns of lactose powder delivered by the OptiNose powder device (Opt-Powder; OptiNose US Inc., Yardley, PA, USA) to that of liquid aerosol administered via a traditional hand-actuated liquid spray pump (Rexam SP270, Rexam Pharma, France). The study was an open-label, crossover design in seven healthy subjects (five females, two males). The regional nasal deposition and clearance patterns of the Opt-Powder device were compared to a traditional liquid spray pump by dynamic gamma camera imaging after administration of either (99m)Tc-labeled lactose powder or liquid (99m)Tc- diethelyne triamine pentaacetic acid-aerosol. The gamma camera images were scaled and aligned with sagittal magnetic resonance images to identify nasal regions. Possible deposition of radiolabeled material in the lungs following both methods of delivery was also evaluated. Both powder and spray were distributed to all of the nasal regions. The Opt-Powder device, however, achieved significantly larger initial deposition in the upper and middle posterior regions of the nose than spray (upper posterior region; Opt-Powder 18.3% ± 11.5 vs. Spray 2.4% ± 1.8, p<0.02; sum of upper and middle posterior regions; Opt-Powder 53.5% ± 18.5 vs. Spray 15.7% ± 13.8, p<0.02). The summed initial deposition to the lower anterior and posterior regions for spray was three times higher compared to Opt-Powder (Opt-Powder 17.4% ± 24.5 vs. Spray 59.4% ± 18.2, p<0.04). OptiNose powder delivery resulted in more rapid overall nasal clearance. No lung deposition was observed. The initial deposition following powder delivery was significantly larger in the ciliated mucosa of the upper and posterior nasal regions, whereas less was deposited in the lower regions. Overall nasal clearance of powder was slower initially, but due to retention in anterior

Intranasal delivery: physicochemical and therapeutic aspects.

PubMed

Costantino, Henry R; Illum, Lisbeth; Brandt, Gordon; Johnson, Paul H; Quay, Steven C

2007-06-07

Interest in intranasal (IN) administration as a non-invasive route for drug delivery continues to grow rapidly. The nasal mucosa offers numerous benefits as a target issue for drug delivery, such as a large surface area for delivery, rapid drug onset, potential for central nervous system delivery, and no first-pass metabolism. A wide variety of therapeutic compounds can be delivered IN, including relatively large molecules such as peptides and proteins, particularly in the presence of permeation enhancers. The current review provides an in-depth discussion of therapeutic aspects of IN delivery including consideration of the intended indication, regimen, and patient population, as well as physicochemical properties of the drug itself. Case examples are provided to illustrate the utility of IN dosing. It is anticipated that the present review will prove useful for formulation scientists considering IN delivery as a delivery route.

The golden ratio of nasal width to nasal bone length.

PubMed

Goynumer, G; Yayla, M; Durukan, B; Wetherilt, L

2011-01-01

To calculate the ratio of fetal nasal width over nasal bone length at 14-39 weeks' gestation in Caucasian women. Fetal nasal bone length and nasal width at 14-39 weeks' gestation were measured in 532 normal fetuses. The mean and standard deviations of fetal nasal bone length, nasal width and their ratio to one another were calculated in normal fetuses according to the gestational age to establish normal values. A positive and linear correlation was detected between the nasal bone length and the gestational week, as between the nasal width and the gestational week. No linear growth pattern was found between the gestational week and the ratio of nasal width to nasal bone length, nearly equal to phi, throughout gestation. The ratio of nasal width to nasal bone length, approximately equal to phi, can be calculated at 14-38 weeks' gestation. This might be useful in evaluating fetal abnormalities.

Nasal polyps

MedlinePlus

... get rid of nasal polyps. Nasal steroid sprays shrink polyps. They help clear blocked nasal passages and ... is stopped. Corticosteroid pills or liquid may also shrink polyps, and can reduce swelling and nasal congestion. ...

Effects of Bifidobacterium Breve Feeding Strategy and Delivery Modes on Experimental Allergic Rhinitis Mice.

PubMed

Ren, Jian-jun; Yu, Zhao; Yang, Feng-Ling; Lv, Dan; Hung, Shi; Zhang, Jie; Lin, Ping; Liu, Shi-Xi; Zhang, Nan; Bachert, Claus

2015-01-01

Different delivery modes may affect the susceptibility to allergic diseases. It is still unknown whether early intervention with probiotics would counteract this effect. The effect of different delivery modes on immune status and nasal symptoms was investigated on established allergic rhinitis (AR) mouse model. In addition, the immunoregulatory effects and mechanisms of different feeding manners with Bifidobacterium breve(B. breve) were examined. Live lyophilized B. breve was orally administered to BALB/c mice born via vaginal delivery(VD) or cesarean delivery (CD) for 8 consecutive weeks, after which they were sensitized by ovalbumin(OVA) to establish experimental AR. Nasal symptoms, serum immunoglobulins, cytokines, splenic percentages of CD4(+)CD25(+)Foxp3(+) regulatory T(Treg) cells and nasal eosinophil infiltration were evaluated. Compared with VD mice, mice delivered via CD demonstrated more serious nasal symptoms, higher concentrations of OVA-specific immunoglobulin (Ig) E, more nasal eosinophils and lower percentages of splenic CD4(+)CD25(+)Foxp3(+)Treg cells after establishing experimental AR. These parameters were reversed by administering B. breves hortly after birth. However, the effect of B. breve did not differ between different delivery modes. CD aggravates the nasal symptoms of AR mice compared to VD. This is the first report that oral administration of B. breve shortly after birth can significantly alleviate the symptoms of AR mice born via both deliveries, probably via activation of the regulatory capacity of CD4(+)CD25(+)Foxp3(+)Treg cells.

Comparison of Nasal Acceleration and Nasalance across Vowels

ERIC Educational Resources Information Center

Thorp, Elias B.; Virnik, Boris T.; Stepp, Cara E.

2013-01-01

Purpose: The purpose of this study was to determine the performance of normalized nasal acceleration (NNA) relative to nasalance as estimates of nasalized versus nonnasalized vowel and sentence productions. Method: Participants were 18 healthy speakers of American English. NNA was measured using a custom sensor, and nasalance was measured using…

Nasal continuous positive airway pressure treatment: current realities and future.

PubMed

Berthon-Jones, M; Lawrence, S; Sullivan, C E; Grunstein, R

1996-11-01

Nasal continuous positive airway pressure (CPAP) is a highly effective treatment for obstructive sleep apnea syndrome. The apnea/hypopnea index (AHI) is reduced 10-fold, but the patient dropout rate is up to 30%, and usage is typically < 5 hours per night. Titration, designed to make the best trade-off between effectiveness and side effects, is expensive. Autotitrating devices make this trade-off on a minute-by-minute basis, potentially reducing mean pressure delivery, reducing side effects, and increasing compliance. The aim of this study was to test the effectiveness of the AutoSet self-adjusting nasal CPAP system (ResMed, Sydney, Australia) in eliminating obstructive events and normalizing the arousal index. Forty-five subjects (41 males and 4 females with AHI) values of > 20/hour were recruited, with written informed consent. Subjects slept for a diagnostic night, followed by a treatment night, in the laboratory, using the AutoSet system with full polysomnographic monitoring of respiratory and sleep variables. Arousals were scored using ASDA criteria. Hypopneas were scored when there was a 50% reduction in ventilation for > 10 seconds, associated with a 4% drop in oxygen saturation. For comparison, the ASDA arousal index in 16 normal subjects (without nasal CPAP) is provided. Results are given as mean +/- standard error of the mean. AHI was reduced from 55 +/- 3 to 1.5 +/- 0.35 events/hour (p < 0.0001). The arousal index was reduced from 65 +/- 3 to 18 +/- 2 events/hour (p < 0.0001), identical to the value in the 16 healthy normal subjects. There was a 158% +/- 21% increase in slow-wave sleep (p = 0.01) and a 186% +/- 27% increase in rapid eye movement sleep (p = 0.013). The AutoSet self-adjusting nasal CPAP system adequately treats obstructive sleep apnea syndrome on the first night under laboratory conditions.

Nasal deposition of ciclesonide nasal aerosol and mometasone aqueous nasal spray in allergic rhinitis patients.

PubMed

Emanuel, Ivor A; Blaiss, Michael S; Meltzer, Eli O; Evans, Philip; Connor, Alyson

2014-01-01

Sensory attributes of intranasal corticosteroids, such as rundown to the back of the throat, may influence patient treatment preferences. This study compares the nasal deposition and nasal retention of a radiolabeled solution of ciclesonide nasal aerosol (CIC-hydrofluoroalkane [HFA]) with a radiolabeled suspension of mometasone furoate monohydrate aqueous nasal spray (MFNS) in subjects with either perennial allergic rhinitis (AR) or seasonal AR. In this open-label, single-dose, randomized, crossover scintigraphy study, 14 subjects with symptomatic AR received a single dose of radiolabeled 74-μg CIC-HFA (37 μg/spray, 1 spray/each nostril) via a nasal metered-dose inhaler or a single dose of radiolabeled 200-μg MFNS (50 μg/spray, 2 sprays/each nostril), with a minimum 5-day washout period between treatments. Initial deposition (2 minutes postdose) of radiolabeled CIC-HFA and MFNS in the nasal cavity, nasopharynx, and on nasal wipes, and retention of radioactivity in the nasal cavity and nasal run-out on nasal wipes at 2, 4, 6, 8, and 10 minutes postdose were quantified with scintigraphy. At 2 and 10 minutes postdose, deposition of radiolabeled CIC-HFA was significantly higher in the nasal cavity versus radiolabeled MFNS (99.42% versus 86.50% at 2 minutes, p = 0.0046; and 81.10% versus 54.31% at 10 minutes, p < 0.0001, respectively; p values unadjusted for multiplicity). Deposition of radioactivity on nasal wipes was significantly higher with MFNS versus CIC-HFA at all five time points, and posterior losses of radiolabeled formulation were significantly higher with MFNS at 6, 8, and 10 minutes postdose. In this scintigraphic study, significantly higher nasal deposition and retention of radiolabeled aerosol CIC-HFA were observed versus radiolabeled aqueous MFNS in subjects with AR.

Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review

PubMed Central

Islam, Mohammad Ariful; Firdous, Jannatul; Choi, Yun-Jaie; Yun, Cheol-Heui; Cho, Chong-Su

2012-01-01

Chitosan, a natural biodegradable polymer, is of great interest in biomedical research due to its excellent properties including bioavailability, nontoxicity, high charge density, and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has gelling properties when it interacts with counterions such as sulfates or polyphosphates and when it crosslinks with glutaraldehyde. This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms. Therefore, chitosan together with the advance of nanotechnology can be effectively applied as a carrier system for vaccine delivery. In fact, chitosan microspheres have been studied as a promising carrier system for mucosal vaccination, especially via the oral and nasal route to induce enhanced immune responses. Moreover, the thiolated form of chitosan is of considerable interest due to its improved mucoadhesivity, permeability, stability, and controlled/extended release profile. This review describes the various methods used to design and synthesize chitosan microspheres and recent updates on their potential applications for oral and nasal delivery of vaccines. The potential use of thiolated chitosan microspheres as next-generation mucosal vaccine carriers is also discussed. PMID:23271909

3-D nasal cultures: Systems toxicological assessment of a candidate modified-risk tobacco product.

PubMed

Iskandar, Anita R; Mathis, Carole; Martin, Florian; Leroy, Patrice; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Trivedi, Keyur; Grandolfo, Davide; Cabanski, Maciej; Guedj, Emmanuel; Merg, Celine; Frentzel, Stefan; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

2017-01-01

In vitro toxicology approaches have evolved from a focus on molecular changes within a cell to understanding of toxicity-related mechanisms in systems that can mimic the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offers a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus, the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. Aligned with 3Rs strategy, this study aimed to explore the relevance of a human 3-D nasal culture model to assess the toxicological impact of aerosols generated from a candidate modified risk tobacco product (cMRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F. A series of experimental repetitions, where multiple concentrations of THS2.2 aerosol and 3R4F smoke were applied, were conducted to obtain reproducible measurements to understand the cellular/molecular changes that occur following exposure. In agreement with "Toxicity Testing in the 21st Century - a Vision and a Strategy", this study implemented a systems toxicology approach and found that for all tested concentrations the impact of 3R4F smoke was substantially greater than that of THS2.2 aerosol in terms of cytotoxicity levels, alterations in tissue morphology, secretion of pro-inflammatory mediators, impaired ciliary function, and increased perturbed transcriptomes and miRNA expression profiles.

The role of nasal corticosteroids in the treatment of rhinitis.

PubMed

Meltzer, Eli O

2011-08-01

Intranasal corticosteroids (INSs) are the first choice for rhinitis pharmacotherapy. This preference is because of their broad range of actions that result in reductions of proinflammatory mediators, cytokines, and cells. Over the past 30 years, INSs have been modified to improve their pharmacodynamic, pharmacokinetic, and delivery system properties, with attention to improving characteristics such as receptor binding affinity, lipophilicity, low systemic bioavailability, and patient preference. Clinically, they have been shown to be the most effective class of nasal medications for treating allergic rhinitis and nonallergic rhinopathy, with no clear evidence that any specific INS is superior to others. Copyright © 2011 Elsevier Inc. All rights reserved.

[The effect of laryngoscopic surgery combined with nasal endoscopic system for the treatment of vocal cords benign lesions].

PubMed

Wang, Weian; Lu, Rong

2013-06-01

To investigate the effect of laryngoscopic surgery combined with nasal endoscopic system for the treatment of vocal cords benign lesions. Fifty-two patients admitted to our department with vocal cords benign lesions (including vocal polyps, vocal nodules, vocal cord cyst) underwent laryngoscopic surgery combined with nasal endoscopic system. All patients were treated successfully once and for all without any significant postoperative complication. The laryngoscopic surgery combined with nasal endoscopic system is a safe, minimally invasive and simple method for the treatment of benign lesions of vocal cords.

Decrease in delivery room intubation rates after use of nasal intermittent positive pressure ventilation in the delivery room for resuscitation of very low birth weight infants.

PubMed

Biniwale, Manoj; Wertheimer, Fiona

2017-07-01

The literature supports minimizing duration of invasive ventilation to decrease lung injury in premature infants. Neonatal Resuscitation Program recommended use of non-invasive ventilation (NIV) in delivery room for infants requiring prolonged respiratory support. To evaluate the impact of implementation of non-invasive ventilation (NIV) using nasal intermittent positive pressure ventilation (NIPPV) for resuscitation in very low birth infants. Retrospective study was performed after NIPPV was introduced in the delivery room and compared with infants receiving face mask to provide positive pressure ventilation for resuscitation of very low birth weight infants prior to its use. Data collected from 119 infants resuscitated using NIPPV and 102 infants resuscitated with a face mask in a single institution. The primary outcome was the need for endotracheal intubation in the delivery room. Data was analyzed using IBM SPSS Statistics software version 24. A total of 31% of infants were intubated in the delivery room in the NIPPV group compared to 85% in the Face mask group (p=<0.001). Chest compression rates were 11% in the NIPPV group and 31% in the Face mask group (p<0.001). Epinephrine administration was also lower in NIPPV group (2% vs. 8%; P=0.03). Only 38% infants remained intubated at 24hours of age in the NIPPV group compared to 66% in the Face mask group (p<0.001). Median duration of invasive ventilation in the NIPPV group was shorter (2days) compared to the Face mask group (11days) (p=0.01). The incidence of air-leaks was not significant between the two groups. NIPPV was safely and effectively used in the delivery room settings to provide respiratory support for VLBW infants with less need for intubation, chest compressions, epinephrine administration and subsequent invasive ventilation. Copyright © 2017 Elsevier B.V. All rights reserved.

Objective Measure of Nasal Air Emission Using Nasal Accelerometry

ERIC Educational Resources Information Center

Cler, Meredith J.; Lien, Yu-An, S.; Braden, Maia N.; Mittleman, Talia; Downing, Kerri; Stepp, Cara, E.

2016-01-01

Purpose: This article describes the development and initial validation of an objective measure of nasal air emission (NAE) using nasal accelerometry. Method: Nasal acceleration and nasal airflow signals were simultaneously recorded while an expert speech language pathologist modeled NAEs at a variety of severity levels. In addition, microphone and…

Evaluation of polyvinylidene fluoride nasal sensor to assess deviated nasal septum in comparision with peak nasal inspiratory flow measurements.

PubMed

Manjunatha, Roopa G; Rajanna, K; Mahapatra, D Roy; Prakash, Surya

2014-01-01

Deviated nasal septum (DNS) is one of the major causes of nasal obstruction. Polyvinylidene fluoride (PVDF) nasal sensor is the new technique developed to assess the nasal obstruction caused by DNS. This study evaluates the PVDF nasal sensor measurements in comparison with PEAK nasal inspiratory flow (PNIF) measurements and visual analog scale (VAS) of nasal obstruction. Because of piezoelectric property, two PVDF nasal sensors provide output voltage signals corresponding to the right and left nostril when they are subjected to nasal airflow. The peak-to-peak amplitude of the voltage signal corresponding to nasal airflow was analyzed to assess the nasal obstruction. PVDF nasal sensor and PNIF were performed on 30 healthy subjects and 30 DNS patients. Receiver operating characteristic was used to analyze the DNS of these two methods. Measurements of PVDF nasal sensor strongly correlated with findings of PNIF (r = 0.67; p < 0.01) in DNS patients. A significant difference (p < 0.001) was observed between PVDF nasal sensor measurements and PNIF measurements of the DNS and the control group. A cutoff between normal and pathological of 0.51 Vp-p for PVDF nasal sensor and 120 L/min for PNIF was calculated. No significant difference in terms of sensitivity of PVDF nasal sensor and PNIF (89.7% versus 82.6%) and specificity (80.5% versus 78.8%) was calculated. The result shows that PVDF measurements closely agree with PNIF findings. Developed PVDF nasal sensor is an objective method that is simple, inexpensive, fast, and portable for determining DNS in clinical practice.

Development of in vitro models to demonstrate the ability of PecSys®, an in situ nasal gelling technology, to reduce nasal run-off and drip

PubMed Central

2013-01-01

Many of the increasing number of intranasal products available for either local or systemic action can be considered sub-optimal, most notably where nasal drip or run-off give rise to discomfort/tolerability issues or reduced/variable efficacy. PecSys, an in situ gelling technology, contains low methoxy (LM) pectin which gels due to interaction with calcium ions present in nasal fluid. PecSys is designed to spray readily, only forming a gel on contact with the mucosal surface. The present study employed two in vitro models to confirm that gelling translates into a reduced potential for drip/run-off: (i) Using an inclined TLC plate treated with a simulated nasal electrolyte solution (SNES), mean drip length [±SD, n = 10] was consistently much shorter for PecSys (1.5 ± 0.4 cm) than non-gelling control (5.8 ± 1.6 cm); (ii) When PecSys was sprayed into a human nasal cavity cast model coated with a substrate containing a physiologically relevant concentration of calcium, PecSys solution was retained at the site of initial deposition with minimal redistribution, and no evidence of run-off/drip anteriorly or down the throat. In contrast, non-gelling control was significantly more mobile and consistently redistributed with run-off towards the throat. Conclusion In both models PecSys significantly reduced the potential for run-off/drip ensuring that more solution remained at the deposition site. In vivo, this enhancement of retention will provide optimum patient acceptability, modulate drug absorption and maximize the ability of drugs to be absorbed across the nasal mucosa and thus reduce variability in drug delivery. PMID:22803832

A novel intranasal breath-powered delivery system for sumatriptan: a review of technology and clinical application of the investigational product AVP-825 in the treatment of migraine.

PubMed

Cady, Roger

2015-01-01

AVP-825, formerly 'OptiNose Sumatriptan,' is an investigational Breath-Powered(TM) Bi-Directional(TM) intranasal delivery system containing low-dose sumatriptan (22 mg intranasal powder) that avoids limitations of other types of intranasal administration by taking advantage of unique features of nasal anatomy and physiology. This review summarizes intranasal drug delivery for migraine, how the breath-powered technology works, and AVP-825 pharmacokinetic, efficacy and safety/tolerability findings. To identify AVP-825 clinical studies, a PubMed/MEDLINE database search was conducted with the terms AVP-825, OptiNose, OptiNose Sumatriptan, Breath-Powered Nasal Delivery or sumatriptan powder. Of 20 articles, 5 clinical studies were identified, including the head-to-head comparative COMPASS trial (AVP-825 vs oral sumatriptan) and two placebo-controlled studies. AVP-825 has faster sumatriptan absorption versus oral tablets or traditional liquid nasal spray. In Phase II/III randomized, double-blind, placebo-controlled trials, AVP-825 produced early and sustained efficacy with minimal triptan-related adverse effects. In COMPASS, AVP-825 produced earlier reduction of migraine pain intensity and migraine-associated symptoms than 100 mg oral sumatriptan, and higher early rates of pain relief and pain freedom, similar sustained efficacy, and fewer atypical sensations. AVP-825 has the potential to provide migraine patients with improved intranasal administration of sumatriptan that may enhance efficacy and tolerability.

Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice.

PubMed

Suzuki, Hidehiko; Nagatake, Takahiro; Nasu, Ayaka; Lan, Huangwenxian; Ikegami, Koji; Setou, Mitsutoshi; Hamazaki, Yoko; Kiyono, Hiroshi; Yagi, Kiyohito; Kondoh, Masuo; Kunisawa, Jun

2018-02-13

Vaccine delivery is an essential element for the development of mucosal vaccine, but it remains to be investigated how physical barriers such as mucus and cilia affect vaccine delivery efficacy. Previously, we reported that C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) targeted claudin-4, which is expressed by the epithelium associated with nasopharynx-associated lymphoid tissue (NALT), and could be effective as a nasal vaccine delivery. Mice lacking tubulin tyrosine ligase-like family, member 1 (Ttll1-KO mice) showed mucus accumulation in nasal cavity due to the impaired motility of respiratory cilia. Ttll1-KO mice nasally immunized with C-CPE fused to pneumococcal surface protein A (PspA-C-CPE) showed reduced PspA-specific nasal IgA responses, impaired germinal center formation, and decreased germinal center B-cells and follicular helper T cells in the NALT. Although there was no change in the expression of claudin-4 in the NALT epithelium in Ttll1-KO mice, the epithelium was covered by a dense mucus that prevented the binding of PspA-C-CPE to NALT. However, administration of expectorant N-acetylcysteine removed the mucus and rescued the PspA-specific nasal IgA response. These results show that the accumulation of mucus caused by impaired respiratory cilia function is an interfering factor in the C-CPE-based claudin-4-targeting nasal vaccine.

Star-shaped poly(oligoethylene glycol) copolymer-based gels: Thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery.

PubMed

Soliman, Mahmoud E; Elmowafy, Enas; Casettari, Luca; Alexander, Cameron

2018-05-30

The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37 °C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in situ gels should have promising application as nasal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Similarity and Enhancement: Nasality from Moroccan Arabic Pharyngeals and Nasals

ERIC Educational Resources Information Center

Zellou, Georgia Eve

2012-01-01

Experimental studies of the articulation, acoustics, and perception of nasal and pharyngeal consonants and adjacent vowels were conducted to investigate nasality in Moroccan Arabic (MA). The status of nasality in MA is described as coarticulatorily complex, where two phoneme types (pharyngeal segments and nasal segments) yield similar…

Canine model of nasal congestion and allergic rhinitis.

PubMed

Tiniakov, Ruslan L; Tiniakova, Olga P; McLeod, Robbie L; Hey, John A; Yeates, Donovan B

2003-05-01

The ragweed- and histamine-induced decreases in nasal patency in cohorts of ragweed-sensitized and nonsensitized dogs were assessed. The volume of nasal airways (V(NA)) was assessed by acoustic rhinometry and resistance to airflow (R(NA)) by anterior rhinomanometry. Histamine delivered to the nasal passages of five dogs caused a rapid and prolonged increase in R(NA) (0.75 +/- 0.26 to 3.56 +/- 0.50 cmH(2)O. l(-1). min), an effect that was reversed by intranasal delivery of aerosolized phenylephrine. Ragweed challenge in five ragweed-sensitized dogs increased R(NA) from 0.16 +/- 0.02 to 0.53 +/- 0.07 cmH(2)O. l(-1). min and decreased V(NA) from 12.5 +/- 1.9 to 3.9 +/- 0.3 cm(3), whereas administration of saline aerosol neither increased R(NA) nor decreased V(NA). Prior administration of d-pseudoephedrine (30 mg po) attenuated the ragweed-induced increase in R(NA) and decrease in V(NA). Ragweed challenge changed neither R(NA) nor V(NA) in four nonsensitized dogs. Mediator-induced nasal congestion and allergen-induced allergic rhinitis in ragweed-sensitized dogs, which exhibit symptoms similar to human disease, can be used in the evaluation of safety and efficacy of antiallergic activity of potential drugs.

Thiomers: potential excipients for non-invasive peptide delivery systems.

PubMed

Bernkop-Schnürch, Andreas; Krauland, Alexander H; Leitner, Verena M; Palmberger, Thomas

2004-09-01

In recent years thiolated polymers or so-called thiomers have appeared as a promising alternative in the arena of non-invasive peptide delivery. Thiomers are generated by the immobilisation of thiol-bearing ligands to mucoadhesive polymeric excipients. By formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of these polymers are improved up to 130-fold. Due to formation of inter- and intramolecular disulfide bonds within the thiomer itself, dosage forms such as tablets or microparticles display strong cohesive properties resulting in comparatively higher stability, prolonged disintegration times and a more controlled release of the embedded peptide drug. The permeation of peptide drugs through mucosa can be improved by the use of thiolated polymers. Additionally some thiomers exhibit improved inhibitory properties towards peptidases. The efficacy of thiomers in non-invasive peptide delivery could be demonstrated by various in vivo studies. Tablets comprising a thiomer and pegylated insulin, for instance, resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Furthermore, a pharmacological efficacy of 1.3% was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Human growth hormone in a thiomer-gel was applied nasally to rats and led to a bioavailability of 2.75%. In all these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. According to these results drug carrier systems based on thiomers seem to be a promising tool for non-invasive peptide drug delivery.

Saline nasal washes

MedlinePlus

... nasal wash helps flush pollen, dust, and other debris from your nasal passages. It also helps remove excess mucus (snot) and adds moisture. Your nasal passages are open spaces behind your nose. Air passes through your nasal ...

[Strategy and collaboration between medicinal chemists and pharmaceutical scientists for drug delivery systems].

PubMed

Mano, Takashi

2013-01-01

In order to successfully apply drug delivery systems (DDS) to new chemical entities (NCEs), collaboration between medicinal chemists and formulation scientists is critical for efficient drug discovery. Formulation scientists have to use 'language' that medicinal chemists understand to help promote mutual understanding, and medicinal chemists and formulation scientists have to set up strategies to use suitable DDS technologies at the discovery phase of the programmes to ensure successful transfer into the development phase. In this review, strategies of solubilisation formulation for oral delivery, inhalation delivery, nasal delivery and bioconjugation are all discussed. For example, for oral drug delivery, multiple initiatives can be proposed to improve the process to select an optimal delivery option for an NCE. From a technical perspective, formulation scientists have to explain the scope and limitations of formulations as some DDS technologies might be applicable only to limited chemical spaces. Other limitations could be the administered dose and, cost, time and resources for formulation development and manufacturing. Since DDS selection is best placed as part of lead-optimisation, formulation scientists need to be involved in discovery projects at lead selection and optimisation stages. The key to success in their collaboration is to facilitate communication between these two areas of expertise at both a strategic and scientific level. Also, it would be beneficial for medicinal chemists and formulation scientists to set common goals to improve the process of collaboration and build long term partnerships to improve DDS.

[Clinical analysis of nasal resistance and pulmonary function testing in patients with chronic nasal-sinusitis and nasal polyps].

PubMed

Liao, Hua; Shen, Ying; Wang, Pengjun

2015-05-01

To study the pulmonary function and nasal resistance characteristics of patients with chronic nose-sinusitis and nasal polyps (CRSwNP), to explore the evaluation role of nasal resistance in nasal ventilation function and the effect of endoscopic sinus surgery on pulmonary function in patients with CRSwNP. Fifty CRSwNP patients that met the study criteria were selected . The patients were performed endoscopic surgeries according to Messerklinger surgical procedures under general anesthesia. Extent of surgery was based on preoperative CT showing the range of the lesion of disease and endoscopic findings. Perioperative treatments contained intranasal corticosteroids, cephalosporin or penicillin antibiotics, nasal irrigation and other treatments. Main outcome measures included visual analog scale (VAS), endoscopic Lind-Kennedy scores, nasal resistence, pulmonary function in patientsone week before and after surgery, three months and six months after surgery. Pulmonary function includes forced expiratory volume in one second (FEV1), forced vital capacity FEV1/FVC and peak expiratory flow (PEF). The study found that there were significantly positive correlations among VAS score, Lund-Kennedy score and nasal resistance (P < 0.05) in CRSwNP patients, but there is a significantly negative correlation between VAS score, Lund-Kennedy score, nasal resistance and pulmonary function indexes of FEV1, FVC and PEF (P < 0.05). The VAS score, Lund-Kennedy score and nasal resistance values of CRSwNP patients were decreased significantly after comprehensive treatments with nasal endoscopic operation as the major one, the difference was statistically different (P < 0.05). And the pulmonary function indexs (FEV1, FVC, PEF) were significantly increased after surgery in CRSwNP patients. The nasal resistance can objectively and reliably reflect the degree of nasal congestion and the recovery of nasal function in CRSwNP patients after endoscopic sinus surgery. The detection method of nasal

Rumen-stable delivery systems.

PubMed

Papas; Wu

1997-12-08

Ruminants have a distinct digestive system which serves a unique symbiotic relationship between the host animal and predominantly anaerobic rumen bacteria and protozoa. Rumen fermentation can be both beneficial by enabling utilization of cellulose and non-protein nitrogen and detrimental by reducing the nutritive value of some carbohydrates, high biological value proteins and by hydrogenating unsaturated lipids. In addition it can also result in the modification and inactivation of many pharmacologically active ingredients administered to the host animal via the oral route. The advances in ruminant nutrition and health demand a rumen-stable delivery system which can deliver the active ingredient post-ruminally while simultaneously meet efficacy, safety and cost criteria. In contrast to drug delivery systems for humans, the demand for low-cost has hindered the development of effective rumen-stable delivery systems. Historically, heat and chemical treatment of feed components, low solubility analogues or lipid-based formulations have been used to achieve some degree of rumen-stability, and products have been developed accordingly. Recently, a polymeric pH-dependent rumen-stable delivery system has been developed and commercialized. The rationale of this delivery system is based on the pH difference between ruminal and abomasal fluids. The delivery system is composed of a basic polymer, a hydrophobic substance and a pigment material. It can be applied as a coating to solid particles via a common encapsulation method such as air-suspension coating. In the future, the delivery system could be used to deliver micronutrients and pharmaceuticals post-ruminally to ruminant animals. A further possible application of the delivery system is that it could also be combined with other controlled delivery devices/systems in order to enhance slow release or to achieve targeted delivery needs for ruminants. This paper discusses the rumen protection and the abomasal release mechanism

Using a high-flow nasal cannula provides superior results to OxyMask delivery in moderate to severe bronchiolitis: a randomized controlled study.

PubMed

Ergul, Ayse Betul; Calıskan, Emrah; Samsa, Hasan; Gokcek, Ikbal; Kaya, Ali; Zararsiz, Gozde Erturk; Torun, Yasemin Altuner

2018-06-18

The effectiveness of using a face mask with a small diffuser for oxygen delivery (OxyMask) was compared to use of a high-flow nasal cannula (HFNC) in patients with moderate or severe bronchiolitis.The study population in this open, phase 4, randomized controlled trial consisted of 60 patients aged 1-24 months diagnosed with moderate or severe bronchiolitis and admitted to an intensive care unit (ICU) for oxygen therapy. The patients were randomized into two groups according to the method of oxygen delivery: a diffuser mask group and an HFNC group.There were seven failures in the mask group and none in the HFNC group. The survival probability differed significantly between the two treatment methods (p = 0.009).Time to weaning off oxygen therapy was 56 h in the HFNC group and 96 h in the mask group (p < 0.001). HFNC use decreased the treatment failure rate and the duration of both oxygen therapy and ICU treatment compared to the diffuser mask, which implies that an HFNC should be the first choice for treating patients admitted to the ICU with severe bronchiolitis. What is known: • A high-flow nasal cannula (HFNC) does not significantly reduce the time on oxygen compared to standard therapy in children with moderate to severe bronchiolitis. Observational studies show that, since the introduction of HFNC, fewer children with bronchiolitis need intubation. For children with moderate to severe bronchiolitis there is no proof of its benefit. What Is New: • In children with moderate to severe bronchiolitis, HFNC provides faster and more effective improvement than can be achieved with a diffuser mask.

Carrier Mediated Systemic Delivery of Protein and Peptide Therapeutics.

PubMed

Zaman, Rahela; Othman, Iekhan; Chowdhury, Ezharul Hoque

2016-01-01

Over the last few decades proteins and peptide therapeutics have occupied an enormous fraction of pharmaceutical industry. Despite their high potential as therapeutics, the big challenge often encountered is the effective administration and bioavailability of protein therapeutics in vivo system. Peptide molecules are well known for their in vivo short half-lives. In addition, due to high molecular weight and susceptibility to enzymatic degradation, often it is not easy to administer peptides and proteins orally or through any other noninvasive routes. Conventional drug management system often demands for frequent and regular interval intravenous/subcutaneous administration, which decreases overall patient compliance and increases chances of side-effects related to dose-fluctuation in systemic circulation. A controlled mode of delivery system could address all these short-comings at a time. Therefore, long-acting sustained release formulations for both invasive and noninvasive routes are under rigorous study currently. Long-acting formulations through invasive routes can address patient compliance and dose-fluctuation issues by less frequent administration. Also, any new route of administration other than invasive routes will address cost-effectiveness of the therapeutic by lessening the need to deal with health professional and health care facility. Although a vast number of studies are dealing with novel drug delivery systems, till now only a handful of controlled release formulations for proteins and peptides have been approved by FDA. This study therefore focuses on current and perspective controlled release formulations of existing and novel protein/peptide therapeutics via conventional invasive routes as well as potential novel non-invasive routes of administration, e.g., oral, buccal, sublingual, nasal, ocular, rectal, vaginal and pulmonary.

Nasal drug delivery: Design of a novel mucoadhesive and in situ gelling polymer.

PubMed

Menzel, Claudia; Jelkmann, Max; Laffleur, Flavia; Bernkop-Schnürch, Andreas

2017-01-30

The aim of the present study was to establish a novel polymeric excipient for liquid nasal dosage forms exhibiting viscosity increasing properties, improved mucoadhesion and stability towards oxidation in solution. In order to achieve this goal, 2-mercaptonicotinic acid was first coupled to l-cysteine by disulfide exchange reaction and after purification directly attached to the polymeric backbone of xanthan gum by carbodiimide mediated amide bond formation. The resulting conjugate was characterized with respect to the amount of coupled ligand, the in situ gelling behavior, mucoadhesive properties and stability towards oxidation. Furthermore, the influence of preactivated polymers on ciliary beat frequency (CBF) of porcine nasal epithelial cells was investigated. Results showed, that 252.52±20.54μmol of the ligand was attached per gram polymer. No free thiol groups could be detected on the polymeric backbone indicating entire preactivation. Rheological investigations of polymer mucus mixtures revealed a 1.7-fold and 2.5-fold enhanced mucoadhesion of entirely preactivated xanthan (Xan-Cys-MNA) compared to thiolated xanthan (Xan-Cys) and unmodified xanthan (Xan). Tensile force evaluation reported a 2.87 and 5.11-fold higher total work of adhesion (TWA) as well as a 1.63 and 2.41-fold higher maximum detachement force of Xan-Cys-MNA compared to Xan-Cys and Xan. In the presence of H 2 O 2 as an oxidizing agent Xan-Cys-MNA showed unlike Xan-Cys no increase in viscosity, indicating high stability towards oxidation. Addition of CaCl 2 to Xan-Cys-MNA solutions caused a decrease in viscosity at nevertheless higher total viscosity. Results from CBF studies proved nasal safety for the novel conjugate. According to these results, entirely preactivated thiolated xanthan gum seems to be a promising excipient for nasal dosage forms in order to improve drug bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

A Nasal Epithelial Receptor for Staphylococcus aureus WTA Governs Adhesion to Epithelial Cells and Modulates Nasal Colonization

PubMed Central

Faulstich, Manuela; Grau, Timo; Severin, Yannik; Unger, Clemens; Hoffmann, Wolfgang H.; Rudel, Thomas; Autenrieth, Ingo B.; Weidenmaier, Christopher

2014-01-01

Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization. PMID:24788600

Nasal mucosal gene expression in patients with allergic rhinitis with and without nasal polyps.

PubMed

Fritz, Stephen B; Terrell, Jeffrey E; Conner, Edward R; Kukowska-Latallo, Jolanta F; Baker, James R

2003-12-01

Nasal polyps are a common problem that is difficult to diagnose and treat, in part because the cause of nasal polyposis is unknown. Although information on the pathogenesis of polyposis is lacking, there are reports suggesting that a genetic predisposition underlies this disorder. We sought to better understand the basis of nasal polyposis associated with allergic rhinitis. We hypothesize that the expression of unique genes is associated with the nasal polyposis phenotype. We examined 12000 human genes transcribed in the nasal mucosa of patients with allergic rhinitis with and without nasal polyps. Biopsy specimens of the mucosa of patients with and without polyps were obtained after the patients refrained from the use of topical or systemic steroid therapy for 2 weeks. Thirty-four genes were differentially expressed between the patient groups, including those for inflammatory molecules and putative growth factors. The greatest differential expression identified by the array analysis was for a group of genes associated with neoplasia, including mammaglobin, a gene transcribed 12-fold higher in patients with polyps compared with control patients with rhinitis alone. Quantitative RT-PCR confirmed this differential expression and documented that the number of mammaglobin mRNA copies is actually 64-fold greater in tissues of patients with polyps versus control patients. The specificity of mammaglobin protein expression was evaluated by means of immunohistochemistry, which showed specific staining in nasal polyp mucosal goblet cells only in patients with polyps. These data suggest that nasal polyposis involves deregulated cell growth, using gene activation in some ways similar to a neoplasm. In addition, mammaglobin, a gene of unknown function associated with breast neoplasia, might be related to polyp growth.

Assessment of nasalance and nasality in patients with a repaired cleft palate.

PubMed

Sinko, Klaus; Gruber, Maike; Jagsch, Reinhold; Roesner, Imme; Baumann, Arnulf; Wutzl, Arno; Denk-Linnert, Doris-Maria

2017-07-01

In patients with a repaired cleft palate, nasality is typically diagnosed by speech language pathologists. In addition, there are various instruments to objectively diagnose nasalance. To explore the potential of nasalance measurements after cleft palate repair by NasalView ® , we correlated perceptual nasality and instrumentally measured nasalance of eight speech items and determined the relationship between sensitivity and specificity of the nasalance measures by receiver-operating characteristics (ROC) analyses and AUC (area under the curve) computation for each single test item and specific item groups. We recruited patients with a primarily repaired cleft palate receiving speech therapy during follow-up. During a single day visit, perceptive and instrumental assessments were obtained in 36 patients and analyzed. The individual perceptual nasality was assigned to one of four categories; the corresponding instrumental nasalance measures for the eight specific speech items were expressed on a metric scale (1-100). With reference to the perceptual diagnoses, we observed 3 nasal and one oral test item with high sensitivity. However, the specificity of the nasality indicating measures was rather low. The four best speech items with the highest sensitivity provided scores ranging from 96.43 to 100%, while the averaged sensitivity of all eight items was below 90%. We conclude that perceptive evaluation of nasality remains state of the art. For clinical follow-up, instrumental nasalance assessment can objectively document subtle changes by analysis of four speech items only. Further studies are warranted to determine the applicability of instrumental nasalance measures in the clinical routine, using discriminative items only.

Intracochlear Drug Delivery Systems

PubMed Central

Borenstein, Jeffrey T.

2011-01-01

Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization.

PubMed

Shah, Brijesh M; Misra, Manju; Shishoo, Chamanlal J; Padh, Harish

2015-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to irreversible loss of neurons, cognition and formation of abnormal protein aggregates. Rivastigmine, a reversible cholinesterase inhibitor used for the treatment of AD, undergoes extensive first-pass metabolism, thus limiting its absolute bioavailability to only 36% after 3-mg dose. Due to extreme aqueous solubility, rivastigmine shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. This investigation was aimed to formulate microemulsion (ME) and mucoadhesive microemulsions (MMEs) of rivastigmine for nose to brain delivery and to compare percentage drug diffused for both systems using in-vitro and ex-vivo study. Rivastigmine-loaded ME and MMEs were prepared by titration method and characterized for drug content, globule size distribution, zeta potential, pH, viscosity and nasal ciliotoxicity study. Rivastigmine-loaded ME system containing 8% w/w Capmul MCM EP, 44% w/w Labrasol:Transcutol-P (1:1) and 48% w/w distilled water was formulated, whereas 0.3% w/w chitosan (CH) and cetyl trimethyl ammonium bromide (as mucoadhesive agents) were used to formulate MMEs, respectively. ME and MMEs formulations were transparent with drug content, globule size and zeta potential in the range of 98.59% to 99.43%, 53.8 nm to 55.4 nm and -2.73 mV to 6.52 mV, respectively. MME containing 0.3% w/w CH followed Higuchi model (r(2) = 0.9773) and showed highest diffusion coefficient. It was free from nasal ciliotoxicity and stable for three months. However, the potential of developed CH-based MME for nose to brain delivery of rivastigmine can only be established after in-vivo and biodistribution study.

Pharmacokinetic evaluation of ipamorelin and other peptidyl growth hormone secretagogues with emphasis on nasal absorption.

PubMed

Johansen, P B; Hansen, K T; Andersen, J V; Johansen, N L

1998-11-01

1. The pharmacokinetics of three new peptidyl growth hormone secretagogues, ipamorelin (NNC 26-0161), NNC 26-0194 and NNC 26-0235, were compared with two well-known hexapeptides, GHRP-2 and GHRP-6, in the male rat following different routes of administration. 2. Following i.v. bolus injection, plasma concentrations of the peptides declined biexponentially. Ipamorelin differed markedly from the other peptides investigated, demonstrating a systemic plasma clearance 5-fold lower than that of GHRP-6. Ipamorelin was mainly excreted in the urine, whereas GHRP-6 was predominantly excreted in the bile. NNC 26-0194 and NNC 26-0235 also showed high biliary excretions. Ipamorelin and the two NNC peptides were moderately resistant towards metabolism as 60-80% of the administered dose could be recovered from bile and urine as intact peptide. 3. After intranasal application, the bioavailability of ipamorelin was estimated at approximately 20%. Higher bioavailabilities of approximately 50% were determined for NNC 26-0235, NNC 26-0194 and GHRP-2, whereas the nasal absorption of GHRP-6 was somewhat lower. Thus, the peptides could be easily transported across the nasal epithelium suggesting that the nasal route seems promising for systemic delivery of this family of peptidyl growth hormone secretagogues.

A novel device for delivery of intranasal particulate medication: a pilot study.

PubMed

Khalili, Sammy; Tkachenko, Natalia; Rotenberg, Brian

2013-11-01

Intranasal medication delivery for allergic rhinitis (AR) is considered a mainstay of therapy but is hampered by poor compliance. Among reasons given are unpleasant sensations associated with spray penetration into the pharynx. Our objective was to study a novel method of particle delivery to the nose that would abrogate these issues. This was a double-blind, randomized study. Subjects who met study criteria underwent intranasal particle delivery using a novel device (Trivair Nasal Deposition System; Trimel Pharmaceuticals, Toronto, Canada) that delivered anhydrous lactose particles into the nose via a transoral air puff (thus elevating soft palate and blocking the nasopharynx). Subjects had nostrils randomized into 4 groups (particle sizes 5 μm and 50 μm × doses 12.5 mg and 25 mg). Particle deposition was assessed at 1 minute, 10 minutes, and 30 minutes on the inferior turbinate, middle turbinate, and nasopharynx, respectively, using high-definition endoscopic photography. Each image was compared using an expert blinded 2-person panel for percentage particles remaining. Nonparametric data was assessed using the Wilcoxon signed-rank test via Strata software. Twelve nostrils in total met study criteria. The results showed no difference in effectiveness of nasal particle retention between the groups based on particle size or dose. No particles entered the nasopharynx or oropharynx. This study provides proof-of-principle data that the Trivair Nasal Deposition System is effective at retaining medication in the nose without pharyngeal penetration. Larger studies on this device are warranted. © 2013 ARS-AAOA, LLC.

Nose and Nasal Planum Neoplasia, Reconstruction.

PubMed

Worley, Deanna R

2016-07-01

Most intranasal lesions are best treated with radiation therapy. Computed tomographic imaging with intravenous contrast is critical for treatment planning. Computed tomographic images of the nose will best assess the integrity of the cribriform plate for central nervous system invasion by a nasal tumor. Because of an owner's emotional response to an altered appearance of their dog's face, discussions need to include the entire family before proceeding with nasal planectomy or radical planectomy. With careful case selection, nasal planectomy and radical planectomy surgeries can be locally curative. Copyright © 2016 Elsevier Inc. All rights reserved.

Kinect based real-time position calibration for nasal endoscopic surgical navigation system

NASA Astrophysics Data System (ADS)

Fan, Jingfan; Yang, Jian; Chu, Yakui; Ma, Shaodong; Wang, Yongtian

2016-03-01

Unanticipated, reactive motion of the patient during skull based tumor resective surgery is the source of the consequence that the nasal endoscopic tracking system is compelled to be recalibrated. To accommodate the calibration process with patient's movement, this paper developed a Kinect based Real-time positional calibration method for nasal endoscopic surgical navigation system. In this method, a Kinect scanner was employed as the acquisition part of the point cloud volumetric reconstruction of the patient's head during surgery. Then, a convex hull based registration algorithm aligned the real-time image of the patient head with a model built upon the CT scans performed in the preoperative preparation to dynamically calibrate the tracking system if a movement was detected. Experimental results confirmed the robustness of the proposed method, presenting a total tracking error within 1 mm under the circumstance of relatively violent motions. These results point out the tracking accuracy can be retained stably and the potential to expedite the calibration of the tracking system against strong interfering conditions, demonstrating high suitability for a wide range of surgical applications.

Thiolated chitosan nanoparticles for the nasal administration of leuprolide: bioavailability and pharmacokinetic characterization.

PubMed

Shahnaz, Gul; Vetter, Anja; Barthelmes, Jan; Rahmat, Deni; Laffleur, Flavia; Iqbal, Javed; Perera, Glen; Schlocker, Wolfgang; Dünnhaput, Sarah; Augustijns, Patrick; Bernkop-Schnürch, Andreas

2012-05-30

The purpose of this study was to develop thiolated nanoparticles to enhance the bioavailability for the nasal application of leuprolide. Thiolated chitosan-thioglycolic acid (chitosan-TGA) and unmodified chitosan nanoparticles (NPs) were developed via ionic gelation with tripolyphosphate (TPP). Leuprolide was incorporated during the formulation process of NPs. The thiolated (chitosan-TGA) NPs had a mean size of 252 ± 82 nm, a zeta potential of +10.9 ± 4 mV, and payload of leuprolide was 12 ± 2.8. Sustained release of leuprolide from thiolated NPs was demonstrated over 6h, which might be attributed to inter- and/or intramolecular disulfide formation within the NPs network. Ciliary beat frequency (CBF) study demonstrated that thiolated NPs can be considered as suitable additives for nasal drug delivery systems. Compared to leuprolide solution, unmodified NPs and thiolated NPs provoked increased leuprolide transport through porcine nasal mucosa by 2.0 and 5.2 folds, respectively. The results of a pharmacokinetic study in male Sprague-Dawley rats showed improved transport of leuprolide from thiolated NPs as compared to leuprolide solution. Thiolated NPs had a 6.9-fold increase in area under the curve, more than 4-fold increase in elimination half-life, and a ∼3.8-fold increase in maximum plasma concentration compared to nasal solution alone. The relative nasal bioavailability (versus s.c. injection) of leuprolide thiolated NPs calculated on the basis of AUC((0-6)) was about 19.6% as compared to leuprolide solution 2.8%. The enhanced bioavailability of leuprolide is likely due to facilitated transport by thiolated NPs rather than improved release. Copyright © 2012. Published by Elsevier B.V.

Nasal Anatomy and Function.

PubMed

Patel, Ruchin G

2017-02-01

The nose is a complex structure important in facial aesthetics and in respiratory physiology. Nasal defects can pose a challenge to reconstructive surgeons who must re-create nasal symmetry while maintaining nasal function. A basic understanding of the underlying nasal anatomy is thus necessary for successful nasal reconstruction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Is Surgical Navigation Useful During Closed Reduction of Nasal Bone Fractures?

PubMed

Kim, Seon Tae; Jung, Joo Hyun; Kang, Il Gyu

2017-05-01

To report the case of a 42-year-old woman with a nasal bone fracture that was easily treated using a surgical navigation system. In this clinical report, the authors suggest that intraoperative surgical navigation systems are useful diagnostically and for localizing sites of nasal bone fractures exactly. The patient underwent successful closed reduction of the nasal bone fracture. Surgical navigation is a useful tool for identifying nasal bone fracture locations and for guiding closed reduction. Surgical navigation is recommended when nasal bone fractures are complicated or not well reduced using the ordinary method.

The efficacy of mobile application use on recall of surgical risks in nasal bone fracture reduction surgery

PubMed Central

Kim, Choong Hyeon; Cheon, Ji Seon; Choi, Woo Young; Son, Kyung Min

2018-01-01

Background The number of surgical risks recalled by a patient after surgery can be used as a parameter for assessing how well the patient has understood the informed consent process. No study has investigated the usefulness of a self-developed mobile application in the traditional informed consent process in patients with a nasal bone fracture. This study aimed to investigate whether delivery of information, such as surgical risks, through a mobile application is more effective than delivery of information through only verbal means and a paper. Methods This prospective, randomized study included 60 patients with a nasal bone fracture. The experimental group (n=30) received preoperative explanation with the traditional informed consent process in addition to a mobile application, while the control group (n=30) received preoperative explanation with only the traditional informed consent process. Four weeks after surgery, the number of recalled surgical risks was compared for analysis. The following six surgical risks were explained: pain, bleeding, nasal deformity, numbness, nasal obstruction, and nasal cartilage necrosis. Results The mean number of recalled surgical risks among all patients was 1.58±0.56. The most frequently recalled surgical risk was nasal deformity in both groups. The mean number of recalled surgical risks was 1.72±0.52 in the experimental group and 1.49±0.57 in the control group. There was a significant association between mobile application use and the mean number of recalled surgical risks (p=0.047). Age, sex, and the level of education were not significantly associated with the mean number of recalled surgical risks. Conclusion This study found that a mobile application could contribute to the efficient delivery of information during the informed consent process. With further improvement, it could be used in other plastic surgeries and other surgeries, and such an application can potentially be used for explaining risks as well as

The efficacy of mobile application use on recall of surgical risks in nasal bone fracture reduction surgery.

PubMed

Kim, Choong Hyeon; Cheon, Ji Seon; Choi, Woo Young; Son, Kyung Min

2018-03-01

The number of surgical risks recalled by a patient after surgery can be used as a parameter for assessing how well the patient has understood the informed consent process. No study has investigated the usefulness of a self-developed mobile application in the traditional informed consent process in patients with a nasal bone fracture. This study aimed to investigate whether delivery of information, such as surgical risks, through a mobile application is more effective than delivery of information through only verbal means and a paper. This prospective, randomized study included 60 patients with a nasal bone fracture. The experimental group (n=30) received preoperative explanation with the traditional informed consent process in addition to a mobile application, while the control group (n=30) received preoperative explanation with only the traditional informed consent process. Four weeks after surgery, the number of recalled surgical risks was compared for analysis. The following six surgical risks were explained: pain, bleeding, nasal deformity, numbness, nasal obstruction, and nasal cartilage necrosis. The mean number of recalled surgical risks among all patients was 1.58±0.56. The most frequently recalled surgical risk was nasal deformity in both groups. The mean number of recalled surgical risks was 1.72±0.52 in the experimental group and 1.49±0.57 in the control group. There was a significant association between mobile application use and the mean number of recalled surgical risks ( p =0.047). Age, sex, and the level of education were not significantly associated with the mean number of recalled surgical risks. This study found that a mobile application could contribute to the efficient delivery of information during the informed consent process. With further improvement, it could be used in other plastic surgeries and other surgeries, and such an application can potentially be used for explaining risks as well as delivering other types of information.

Island composite nasal flap for nasal dorsum skin defects.

PubMed

Skitarelić, Neven; Mladina, Ranko; Mraovic, Boris; Simurina, Tatjana; Skitarelić, Nataa; Vuković, Katarina

2009-08-01

Skin defects on the nasal dorsum remain a challenge for the plastic surgeon. There are few local nasal flap options for the repair of proximally positioned nasal skin defects. During a 3-year period, 22 patients were treated after excision of skin cancer in the proximal two-thirds of the nose. Nine patients (41%) were female and 13 (59%) were male, with an average age of 69 years. All patients were operated on under local anesthesia. The average follow-up was 25 months. In all patients, after tumor ablation, the skin defect was closed with an island composite nasal skin flap. Pathohistologic analysis confirmed that the margins of the removed tumor were free of malignant cells. Six patients (27.3%) had squamous cell and 16 (72.7%) had basal cell carcinoma. There was no total or partial flap loss. None of the patients has suffered from recurrence of the tumor. The island composite nasal flap is a reliable technique for the closure of proximal nasal skin defects. Complications in the elevation of the island composite flap were rare, and the final result was acceptable.

Correlation of Nasal Mucosal Temperature With Subjective Nasal Patency in Healthy Individuals

PubMed Central

Bailey, Ryan S.; Casey, Kevin P.; Pawar, Sachin S.; Garcia, Guilherme J. M.

2016-01-01

Importance Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort. Objective To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy subjects. Design, Setting, and Participants Twenty-two healthy adults were recruited for this study. Subjects first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale (VAS) to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in two locations along the nasal septum: at the vestibule and across from the inferior turbinate head. Results The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (ΔTexp-insp = 6.2 ± 2.6°C) than during resting breathing (ΔTexp-insp = 4.2 ± 2.3°C) in both locations (p < 10−13). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side VAS score (Pearson r = −0.55, p=0.0076) and NOSE score (Pearson r = −0.47, p=0.028). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower in the first cavity to be measured, which was the right cavity in all subjects. Conclusions and Relevance The greater mucosal temperature oscillations during deep breathing is consistent with the common experience that airflow sensation is enhanced during deep breaths, thus supporting the hypothesis that mucosal cooling plays a central role in nasal airflow sensation

Influence of cooling face masks on nasal air conditioning and nasal geometry.

PubMed

Lindemann, J; Hoffmann, T; Koehl, A; Walz, E M; Sommer, F

2017-06-01

Nasal geometries and temperature of the nasal mucosa are the primary factors affecting nasal air conditioning. Data on intranasal air conditioning after provoking the trigeminal nerve with a cold stimulus simulating the effects of an arctic condition is still missing. The objective was to investigate the influence of skin cooling face masks on nasal air conditioning, mucosal temperature and nasal geometry. Standardized in vivo measurements of intranasal air temperature, humidity and mucosal temperature were performed in 55 healthy subjects at defined detection sites before and after wearing a cooling face mask. Measurements of skin temperature, rhinomanometry and acoustic rhinometry were accomplished. After wearing the face mask the facial skin temperature was significantly reduced. Intranasal air temperature did not change. Absolute humidity and mucosal temperature increased significantly. The acoustic rhinometric results showed a significant increase of the volumes and the cross-sectional areas. There was no change in nasal airflow. Nasal mucosal temperature, humidity of inhaled air, and volume of the anterior nose increased after application of a cold face mask. The response is mediated by the trigeminal nerve. Increased mucosal temperatures as well as changes in nasal geometries seem to guarantee sufficient steady intranasal nasal air conditioning.

Reduced nasal growth after primary nasal repair combined with cleft lip surgery.

PubMed

Yoshimura, Y; Okumoto, T; Iijima, Y; Inoue, Y

2015-11-01

Nasal growth after cleft lip surgery with or without primary nasal repair was evaluated using lateral cephalograms. In 14 patients who underwent simultaneous nasal repair with primary cleft lip repair and 12 patients without simultaneous nasal repair, lateral cephalograms were obtained at 5 and 10 years of age. Lateral cephalograms of normal Japanese children were used as a control. At 5 years of age, there were significant differences in the nasal height and columellar angle among the three groups. Children without simultaneous nasal repair had shorter noses with more upward tilt of the columella compared with the controls, while children with simultaneous nasal repair had much shorter noses and more upward tilt than those without repair. At 10 years of age, the children without simultaneous nasal repair showed no differences from the control group, while those with simultaneous repair still had shorter noses and more upward tilt of the columella. These findings suggest that performing nasal repair at the same time as primary cleft lip surgery has an adverse influence on the subsequent growth of the nose. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

A review of nasal polyposis

PubMed Central

Newton, Jonathan Ray; Ah-See, Kim Wong

2008-01-01

Nasal polyps are common, affecting up to four percent of the population. Their etiology remains unclear, but they are known to have associations with allergy, asthma, infection, cystic fibrosis, and aspirin sensitivity. They present with nasal obstruction, anosmia, rhinorrhoea, post nasal drip, and less commonly facial pain. Clinical examination reveals single or multiple grey polypoid masses in the nasal cavity. Computerized tomography allows evaluation of the extent of the disease and is essential if surgical treatment is to be considered. Management of polyposis involves a combination of medical therapy and surgery. There is good evidence for the use of corticosteroids (systemic and topical) both as primary treatment and as postoperative prophylaxis against recurrence. Surgical treatment has been refined significantly over the past twenty years with the advent of endoscopic sinus surgery and, in general, is reserved for cases refractory to medical treatment. Recurrence of the polyposis is common with severe disease recurring in up to ten percent of patients. PMID:18728843

[Endoscopic treatment of small osteoma of nasal sinuses manifested as nasal and facial pain].

PubMed

Li, Yu; Zheng, Tianqi; Li, Zhong; Deng, Hongyuan; Guo, Chaoxian

2015-12-01

To discuss the clinical features, diagnosis and endoscopic surgical intervention for small steoma of nasal sinuses causing nasal and facial pain. A retrospective review was performed on 21 patients with nasal and facial pain caused by small osteoma of nasal sinuses, and nasal endoscopic surgery was included in the treatment of all cases. The nasal and facial pain of all the patients was relieved. Except for one ase exhibiting periorbital bruise after operation, the other patients showed no postoperative complications. Nasal and facial pain caused by small osteoma of nasal sinuses was clinically rare, mostly due to the neuropathic pain of nose and face caused by local compression resulting from the expansion of osteoma. Early diagnosis and operative treatment can significantly relieve nasal and facial pain.

Distilled water nasal provocation in hyperreactive patients.

PubMed

Baudoin, T; Anzic, S A; Kalogjera, L

1999-01-01

Nonisotonic aerosol may act as a provocation agent in the upper and lower airways of hyperreactive individuals. The purpose of the study was to compare the results of nasal challenge with distilled water in patients with allergic rhinitis to those with noninfective nonallergic rhinitis (NINAR), with respect to the potential clinical use of the obtained data. A group of 68 ambulatory patients with allergic rhinitis or NINAR (39 perennial allergic, 6 seasonal, 23 NINAR) were challenged with 10 mL of distilled water aerosol after the baseline active anterior rhinomanometry. Patients with nasal polyposis at endoscopy, significant unilateral septal deviation, positive bacteriologic swab, recent nasal surgery, and uncertain anamnestic data about the medication taken 6 weeks before the provocation were excluded from the study. After 10 minutes of nasal provocation, rhinomanometry was repeated to assess the response. In 15 patients of the perennial allergic group, the same measurements were performed after a 2-week oral antihistamine and topical steroid therapy. Nasal resistance was significantly increased on the more patent side of the nose after nasal provocation with distilled water aerosol in allergic patients in comparison to the nasal resistance before provocation. In the patients with NINAR, the provocation resulted in a significant rise on the more patent side, but the total nasal airway resistance (NAR) levels were also significantly increased. The systemic antihistamine and topical steroid 2-week therapy in patients with perennial allergic rhinitis significantly reduced the response to nasal distilled water provocation. Nasal provocation with distilled water aerosol is a cheap, simple, and acceptable method that provides useful clinical data on the level of nonspecific nasal hyperreactivity and the therapy success.

CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

PubMed

Dal Monte, Olga; Noble, Pamela L; Turchi, Janita; Cummins, Alex; Averbeck, Bruno B

2014-01-01

Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

Oxymetazoline Nasal Spray

MedlinePlus

... is recommended by a doctor. Children 6 to 12 years of age should use oxymetazoline nasal spray carefully and under adult supervision. Oxymetazoline is in a class of medications called nasal decongestants. It works by narrowing the blood vessels in the nasal passages.

Validation of polyvinylidene fluoride nasal sensor to assess nasal obstruction in comparison with subjective technique.

PubMed

Roopa Manjunatha, G; Mahapatra, D Roy; Prakash, Surya; Rajanna, K

2015-01-01

The aim of this study is to validate the applicability of the PolyVinyliDene Fluoride (PVDF) nasal sensor to assess the nasal airflow, in healthy subjects and patients with nasal obstruction and to correlate the results with the score of Visual Analogue Scale (VAS). PVDF nasal sensor and VAS measurements were carried out in 50 subjects (25-healthy subjects and 25 patients). The VAS score of nasal obstruction and peak-to-peak amplitude (Vp-p) of nasal cycle measured by PVDF nasal sensors were analyzed for right nostril (RN) and left nostril (LN) in both the groups. Spearman's rho correlation was calculated. The relationship between PVDF nasal sensor measurements and severity of nasal obstruction (VAS score) were assessed by ANOVA. In healthy group, the measurement of nasal airflow by PVDF nasal sensor for RN and LN were found to be 51.14±5.87% and 48.85±5.87%, respectively. In patient group, PVDF nasal sensor indicated lesser nasal airflow in the blocked nostrils (RN: 23.33±10.54% and LN: 32.24±11.54%). Moderate correlation was observed in healthy group (r=-0.710, p<0.001 for RN and r=-0.651, p<0.001 for LN), and moderate to strong correlation in patient group (r=-0.751, p<0.01 for RN and r=-0.885, p<0.0001 for LN). PVDF nasal sensor method is a newly developed technique for measuring the nasal airflow. Moderate to strong correlation was observed between PVDF nasal sensor data and VAS scores for nasal obstruction. In our present study, PVDF nasal sensor technique successfully differentiated between healthy subjects and patients with nasal obstruction. Additionally, it can also assess severity of nasal obstruction in comparison with VAS. Thus, we propose that the PVDF nasal sensor technique could be used as a new diagnostic method to evaluate nasal obstruction in routine clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Peptide and protein delivery using new drug delivery systems.

PubMed

Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

2013-01-01

Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.

Biomaterials for drug delivery systems.

PubMed

Buckles, R G

1983-01-01

Drug delivery systems have unusual materials requirements which derive mainly from their therapeutic role: to administer drugs over prolonged periods of time at rates that are independent of patient-to-patient variables. The chemical nature of the surfaces of such devices may stimulate biorejection processes which can be enhanced or suppressed by the simultaneous presence of the drug that is being administered. Selection of materials for such systems is further complicated by the need for compatibility with the drug contained within the system. A review of selected drug delivery systems is presented. This leads to a definition of the technologies required to develop successfully such systems as well as to categorize the classes of drug delivery systems available to the therapist. A summary of the applications of drug delivery systems will also be presented. There are five major challenges to the biomaterials scientist: (1) how to minimize the influence on delivery rate of the transient biological response that accompanies implantation of any object; (2) how to select a composition, size, shape, and flexibility that optimizes biocompatibility; (3) how to make an intravascular delivery system that will retain long-term functionality; (4) how to make a percutaneous lead for those delivery systems that cannot be implanted but which must retain functionality for extended periods; and (5) how to make biosensors of adequate compatibility and stability to use with the ultimate drug delivery system-a system that operates with feedback control.

Correlation of Nasal Mucosal Temperature With Subjective Nasal Patency in Healthy Individuals.

PubMed

Bailey, Ryan S; Casey, Kevin P; Pawar, Sachin S; Garcia, Guilherme J M

2017-01-01

Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort. To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy individuals. Healthy adult volunteers first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in 2 locations along the nasal septum: at the vestibule and across from the inferior turbinate head. Nasal mucosal temperature and subjective patency scores in healthy individuals. The 22 healthy adult volunteers (12 [55%] male; mean [SD] age, 28.3 [7.0] years) had a mean (SD) NOSE score of 5.9 (8.4) (range, 0-30) and unilateral VAS score of 1.2 (1.4) (range, 0-5). The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (mean [SD] change in temperature, 6.2°C [2.6°C]) than during resting breathing (mean [SD] change in temperature, 4.2°C [2.3°C]) in both locations (P < .001). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side visual analog scale score (Pearson r = -0.55; 95% CI, -0.79 to -0.17; P = .008) and NOSE score (Pearson r = -0.47; 95% CI, -0.74 to -0.06; P = .03). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower (mean of 1.5°C lower) in the first cavity to be measured, which was the right cavity in all

Is the use of benzalkonium chloride as a preservative for nasal formulations a safety concern? A cautionary note based on compromised mucociliary transport.

PubMed

Bernstein, I L

2000-01-01

Topical nasal solution and suspension delivery systems are available for short- and long-acting vasoconstrictors, ipratropium, cromolyn, azelastine, and glucocorticosteroids. The use of intranasal glucocorticosteroids has increased substantially because the efficacy of these agents has been well established for the treatment of perennial and seasonal allergic rhinitis. Adverse local effects of burning, irritation, and dryness are occasionally associated with glucocorticosteroid nasal preparations. Benzalkonium chloride (BKC) is a quaternary ammonium antimicrobial agent included in some nasal solutions (including glucocorticosteroids) to prevent the growth of bacteria. Some reports suggest that BKC in nasal sprays may cause adverse effects, including reduced mucociliary transport, rhinitis medicamentosa, and neutrophil dysfunction. This article summarizes recent literature about possible adverse biologic effects associated with BKC as a nasal spray preservative by examining its effects on the following properties of mucociliary transport: ciliary motion, ciliary form, ciliary beat frequency, electron microscopy, and particle movement/saccharin clearance tests. Both animal and human in vitro data suggest that BKC promotes ciliostasis and reduction in mucociliary transport that may be partially masked by absorption and dilution effects occurring in respiratory mucus. These possible confounding factors may account for several disparate human in vivo results. The use of BKC-free glucocorticosteroid formulations should be considered, particularly in patients who complain of nasal burning, dryness, or irritation.

Nasal Cancer

MedlinePlus

... the way to your throat as you breathe. Cancer of the nasal cavity and paranasal sinuses is ... be like those of infections. Doctors diagnose nasal cancer with imaging tests, lighted tube-like instruments that ...

An exposure system for measuring nasal and lung uptake of vapors in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dahl, A.R.; Brookins, L.K.; Gerde, P.

1995-12-01

Inhaled gases and vapors often produce biological damage in the nasal cavity and lower respiratory tract. The specific site within the respirator tract at which a gas or vapor is absorbed strongly influences the tissues at risk to potential toxic effects; to predict or to explain tissue or cell specific toxicity of inhaled gases or vapors, the sites at which they are absorbed must be known. The purpose of the work reported here was to develop a system for determining nose and lung absorption of vapors in rats, an animal commonly used in inhalation toxicity studies. In summary, the exposuremore » system described allows us to measure in the rate: (1) nasal absorption and desorption of vapors; (2) net lung uptake of vapors; and (3) the effects of changed breathing parameters on vapor uptake.« less

Continuing Professional Education Delivery Systems.

ERIC Educational Resources Information Center

Weeks, James P.

This investigation of delivery systems for continuing professional education provides an overview of current operational delivery systems in continuing professional education, drawing on experience as found in the literature. Learning theories and conclusions are woven into the descriptive text. Delivery systems profiled in the paper include the…

A pilot study of direct delivery of hydroxypropyl-beta-cyclodextrin to the lung by the nasal route in a mouse model of Niemann-Pick C1 disease: motor performance is unaltered and lung disease is worsened.

PubMed

Erickson, Robert P; Deutsch, Gail; Patil, Ruturaj

2018-05-01

We have tested the efficacy of hydroxypropyl-beta-cyclodextrin (HPBCD) delivered by the nasal route in the mouse model of juvenile Niemann-Pick C1 disease (NPC1), as pulmonary disease has not responded to systemic therapy with this drug. Since mice have no gag reflex, coating of the nasal cavity, with possible access to the brain, would be followed by delivery of HPBCD to the lung. While foamy macrophages, containing stored cholesterol, were found in the Npc1 nmf164 homozygous mice, a marked inflammatory response was found with inhaled HPBCD, both in mutant and wild-type animals. Slight inflammation also occasionally occurred with saline inhalation. There was no difference between the saline-treated, HPBCD-treated, and untreated Npc1 nmf164 homozygous mice for weight, balance beam performance, or coat hanger performance. Interestingly, there was a trend to longer survival in the HPBCD-treated Npc1 nmf164 homozygous mice, which, when combined with the survival times of the saline-treated survivals (each of which was not different), became significant.

Nasal Physiology

MedlinePlus

... Anatomy Virtual Anatomy Disclosure Statement Printer Friendly Nasal Physiology Jeremiah A. Alt, MD, PhD Noam Cohen, MD, ... control the inflammation. CONCLUSION An understanding of the physiology of the nose is critical to understand nasal ...

Adenosine-Associated Delivery Systems

PubMed Central

Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

2016-01-01

Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

Assessment of nasal spray deposition pattern in a silicone human nose model using a color-based method.

PubMed

Kundoor, Vipra; Dalby, Richard N

2010-01-01

To develop a simple and inexpensive method to visualize and quantify droplet deposition patterns. Deposition pattern was determined by uniformly coating the nose model with Sar-Gel (a paste that changes from white to purple on contact with water) and subsequently discharging sprays into the nose model. The color change was captured using a digital camera and analyzed using Adobe Photoshop. Several tests were conducted to validate the method. Deposition patterns of different nasal sprays (Ayr, Afrin, and Zicam) and different nasal drug delivery devices (Afrin nasal spray and PARI Sinustar nasal nebulizer) were compared. We also used the method to evaluate the effect of inhaled flow rate on nasal spray deposition. There was a significant difference in the deposition area for Ayr, Afrin, and Zicam. The deposition areas of Afrin nasal spray and PARI Sinustar nasal nebulizer (2 min and 5 min) were significantly different. Inhaled flow rate did not have a significant effect on the deposition pattern. Lower viscosity formulations (Ayr, Afrin) provided greater coverage than the higher viscosity formulation (Zicam). The nebulizer covered a greater surface area than the spray pump we evaluated. Aerosol deposition in the nose model was not affected by air flow conditions.

In Silico Models of Aerosol Delivery to the Respiratory Tract – Development and Applications

PubMed Central

Longest, P. Worth; Holbrook, Landon T.

2011-01-01

This review discusses the application of computational models to simulate the transport and deposition of inhaled pharmaceutical aerosols from the site of particle or droplet formation to deposition within the respiratory tract. Traditional one-dimensional (1-D) whole-lung models are discussed briefly followed by a more in-depth review of three-dimensional (3-D) computational fluid dynamics (CFD) simulations. The review of CFD models is organized into sections covering transport and deposition within the inhaler device, the extrathoracic (oral and nasal) region, conducting airways, and alveolar space. For each section, a general review of significant contributions and advancements in the area of simulating pharmaceutical aerosols is provided followed by a more in-depth application or case study that highlights the challenges, utility, and benefits of in silico models. Specific applications presented include the optimization of an existing spray inhaler, development of charge-targeted delivery, specification of conditions for optimal nasal delivery, analysis of a new condensational delivery approach, and an evaluation of targeted delivery using magnetic aerosols. The review concludes with recommendations on the need for more refined model validations, use of a concurrent experimental and CFD approach for developing aerosol delivery systems, and development of a stochastic individual path (SIP) model of aerosol transport and deposition throughout the respiratory tract. PMID:21640772

Humidification of inspired oxygen is increased with pre-nasal cannula, compared to intranasal cannula.

PubMed

Dellweg, Dominic; Wenze, Markus; Hoehn, Ekkehard; Bourgund, Olaf; Haidl, Peter

2013-08-01

Oxygen therapy is usually combined with a humidification device, to prevent mucosal dryness. Depending on the cannula design, oxygen can be administered pre- or intra-nasally (administration of oxygen in front of the nasal ostia vs cannula system inside the nasal vestibulum). The impact of cannula design on intra-nasal humidity, however, has not been investigated to date. First, to develop a system, that samples air from the nasal cavity and analyzes the humidity of these samples. Second, to investigate nasal humidity during pre-nasal and intra-nasal oxygen application, with and without humidification. We first developed and validated a sampling and analysis system to measure humidity from air samples. By means of this system we measured inspiratory air samples from 12 subjects who received nasal oxygen with an intra-nasal and pre-nasal cannula at different flows, with and without humidification. The sampling and analysis system showed good correlation to a standard hygrometer within the tested humidity range (r = 0.99, P < .001). In our subjects intranasal humidity dropped significantly, from 40.3 ± 8.7% to 35.3 ± 5.8%, 32 ± 5.6%, and 29.0 ± 6.8% at flows of 1, 2, and 3 L, respectively, when oxygen was given intra-nasally without humidification (P = .001, P < .001, and P < .001, respectively). We observed no significant change in airway humidity when oxygen was given pre-nasally without humidification. With the addition of humidification we observed no significant change in humidity at any flow, and independent of pre- or intranasal oxygen administration. Pre-nasal administration of dry oxygen achieves levels of intranasal humidity similar to those achieved by intranasal administration in combination with a bubble through humidifier. Pre-nasal oxygen simplifies application and may reduce therapy cost.

Delivery of salmon calcitonin using a microneedle patch

PubMed Central

Tas, Cetin; Mansoor, Saffar; Kalluri, Haripriya; Zarnitsyn, Vladimir G.; Choi, Seong-O; Banga, Ajay K.; Prausnitz, Mark R.

2011-01-01

Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to carry out an injection. The aim of this study was to develop a transdermal patch containing microneedles (MNs) coated with a peptide drug, salmon calcitonin (sCT), as an alternative to traditional subcutaneous and nasal delivery routes. Quantitative analysis of sCT after coating and drying onto microneedles was performed with a validated HPLC method. In vivo studies were carried out on hairless rats and serum levels of sCT were determined by ELISA. The AUC value of MNs coated with a trehalose-containing formulation (250 ± 83 ng/mL.min) was not significantly different as compared to subcutaneous injections (403 ± 253 ng/mL.min), but approximately 13 times higher than nasal administration (18.4 ± 14.5 ng/mL.min). Tmax (7.5 ± 5 min) values for MN mediated administration were 50% shorter than subcutaneous injections (15 min), possibly due to rapid sCT dissolution and absorption by dermal capillaries. These results suggest that with further optimization of coating formulations, microneedles may enable administration of sCT and other peptides without the need for hypodermic injections. PMID:22172290

Nasal computed tomography.

PubMed

Kuehn, Ned F

2006-05-01

Chronic nasal disease is often a challenge to diagnose. Computed tomography greatly enhances the ability to diagnose chronic nasal disease in dogs and cats. Nasal computed tomography provides detailed information regarding the extent of disease, accurate discrimination of neoplastic versus nonneoplastic diseases, and identification of areas of the nose to examine rhinoscopically and suspicious regions to target for biopsy.

Formulations for Intranasal Delivery of Pharmacological Agents to Combat Brain Disease: A New Opportunity to Tackle GBM?

PubMed Central

van Woensel, Matthias; Wauthoz, Nathalie; Rosière, Rémi; Amighi, Karim; Mathieu, Véronique; Lefranc, Florence; van Gool, Stefaan W.; de Vleeschouwer, Steven

2013-01-01

Despite recent advances in tumor imaging and chemoradiotherapy, the median overall survival of patients diagnosed with glioblastoma multiforme does not exceed 15 months. Infiltration of glioma cells into the brain parenchyma, and the blood-brain barrier are important hurdles to further increase the efficacy of classic therapeutic tools. Local administration methods of therapeutic agents, such as convection enhanced delivery and intracerebral injections, are often associated with adverse events. The intranasal pathway has been proposed as a non-invasive alternative route to deliver therapeutics to the brain. This route will bypass the blood-brain barrier and limit systemic side effects. Upon presentation at the nasal cavity, pharmacological agents reach the brain via the olfactory and trigeminal nerves. Recently, formulations have been developed to further enhance this nose-to-brain transport, mainly with the use of nanoparticles. In this review, the focus will be on formulations of pharmacological agents, which increase the nasal permeation of hydrophilic agents to the brain, improve delivery at a constant and slow release rate, protect therapeutics from degradation along the pathway, increase mucoadhesion, and facilitate overall nasal transport. A mounting body of evidence is accumulating that the underexplored intranasal delivery route might represent a major breakthrough to combat glioblastoma. PMID:24202332

Perception of Better Nasal Patency Correlates with Increased Mucosal Cooling after Surgery for Nasal Obstruction

NASA Astrophysics Data System (ADS)

Garcia, Guilherme; Sullivan, Corbin; Frank-Ito, Dennis; Kimbell, Julia; Rhee, John

2014-11-01

Nasal airway obstruction (NAO) is a common health problem with 340,000 patients undergoing surgery annually in the United States. Traditionally, otolaryngologists have focused on airspace cross-sectional areas and nasal resistance to airflow as objective measures of nasal patency, but neither of these variables correlated consistently with patients' symptoms. Given that the sensation of nasal airflow is also associated with mucosal cooling (i.e., heat loss) during inspiration, we investigated the correlation between the sensation of nasal obstruction and mucosal cooling in 10 patients before and after NAO surgery. Three-dimensional models of the nasal anatomy were created based on pre- and post-surgery computed tomography scans. Computational fluid dynamics (CFD) simulations were conducted to quantify nasal resistance and mucosal cooling. Patient-reported symptoms were measured by a visual analog scale and the Nasal Obstruction Symptom Evaluation (NOSE), a disease-specific quality of life questionnaire. Our results revealed that the subjective sensation of nasal obstruction correlated with both nasal resistance and heat loss, but the strongest correlation was between the NOSE score and the nasal surface area where heat flux exceeds 50 W /m2 . In conclusion, a significant post-operative increase in mucosal cooling correlates well with patients' perception of better nasal patency after NAO surgery.

Colloidal drug delivery system: amplify the ocular delivery.

PubMed

Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

2016-01-01

The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

[Clinical effects of nasal glucocorticoid on amelioration of nasal obstruction in patients with persistent non-allergic rhinitis].

PubMed

Sail, Giyab A; Zuo, Ke-jun; Xu, Geng

2009-09-01

To observe the efficacy of nasal glucocorticoid continuously used for 12 weeks on nasal obstruction in patients with persistent non-allergic rhinitis (PNAR). The changes of nasal obstruction, nasal resistance, nasal mucous membrane and quality of life in 47 patients with PNAR were observed. The efficacy of nasal glucocorticoid (Mometasone Furoate Nasal Spray, MFNS 200 microg/day) on patients with PNAR was evaluated. The results of nasal glucocorticoid (MFNS) continuously used for 12 weeks demonstrated: (1) After treatment, the nasal obstruction, nasal discharge, nasal obstruction related dizziness, headache, hyposmia, daily life activity, whole body fatigue, mental status were significantly improved (P < 0.05). (2) Nasal resistance showed significant amelioration (pre-treatment = 0.28 +/- 0.10, post- treatment = 0.16 +/- 0.05; F = 91.471, P < 0.05). (3) SF-36 questionnaire revealed that role physical, bodily pain, general health, role emotional had significant amelioration (P < 0.01). (4) SNOT-20 questionnaire revealed that the defatigation, impaired concentration, pinch the nose, nasal discharging into the throat, sleep quality had significant amelioration (P < 0.01). (5) Continued treatment for 12 weeks was better than 4 weeks, continued treatment had good effect. The study shows that nasal glucocorticoid improved the nasal obstruction, nasal resistance, nasal mucous membrane and quality of life in patients with PNAR.

Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties.

PubMed

Rygg, Alex; Hindle, Michael; Longest, P Worth

2016-04-01

The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

Immediate effect of benzalkonium chloride in decongestant nasal spray on the human nasal mucosal temperature.

PubMed

Lindemann, J; Leiacker, R; Wiesmiller, K; Rettinger, G; Keck, T

2004-08-01

Benzalkonium chloride is a preservative commonly used in nasal decongestant sprays. It has been suggested that benzalkonium chloride may be harmful to the nasal mucosa. Decongestion with the vasoconstrictor xylometazoline containing benzalkonium chloride has been shown to cause a significant reduction of the nasal mucosal temperature. The purpose of the present study was to determine the short-term influence of xylometazoline nasal spray with and without benzalkonium chloride on the nasal mucosal temperature. Healthy volunteers (30) were included in the study. Fifteen volunteers received xylometazoline nasal spray (1.0 mg/mL) containing benzalkonium chloride (0.1 mg/mL) and 15 age-matched subjects, received xylometazoline nasal spray without benzalkonium chloride. Using a miniaturized thermocouple the septal mucosal temperature was continuously measured at defined intranasal detection sites before and after application of the nasal spray. The mucosal temperature values did not significantly differ between the group receiving xylometazoline containing benzalkonium chloride and the group receiving xylometazoline spray without benzalkonium chloride before and after decongestion (P > 0.05). In both study groups septal mucosal temperatures significantly decreased after decongestion (P < 0.05) because of a reduction of the nasal mucosal blood flow following vasoconstriction. This study indicates that benzalkonium chloride itself does not seem to influence nasal blood flow and nasal mucosal temperature in topical nasal decongestants.

MEMS: Enabled Drug Delivery Systems.

PubMed

Cobo, Angelica; Sheybani, Roya; Meng, Ellis

2015-05-01

Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A preliminary report on the effects of paclitaxel-impregnated stents on sheep nasal mucosa.

PubMed

Herrmann, Brian W; Citardi, Martin J; Vogler, George; Gardner, Laura; Smith, Greg; Javer, Amin R; Burt, Helen M; Jackson, John; Kuhn, Frederick A

2004-01-01

Traditional frontal sinus stents serve only as mechanical devices. It has been proposed that stents also may serve as drug-delivery systems for the topical application of drugs that minimize postoperative scarring. Paclitaxel (Taxol), which has recognized antiscarring effects, may be incorporated via a polymeric formulation into standard rubber stents. The impact of topically applied paclitaxel on the morphology of the nasal mucosa is unknown. An adult sheep model was used for this study. A modified rubber T-tube stent (incorporating paclitaxel at varying dosages) was secured to each side of the septum in four animals (eight sides). An unmodified T-tube was placed on each side of one animal, a T-tube with the drug carrier (but no paclitaxel) was placed on each side of the second animal, and T-tubes with varying paclitaxel were placed on each side of the final two animals. After 4 weeks, animals were killed and the nasal mucosa was harvested. The nasal mucosa was sectioned and stained with hematoxylin and eosin. A pathologist then assessed the nasal mucosa for vascular congestion, glandular atrophy, chronic inflammation, mucosal metaplasia, and mucosal ulceration. No consistent histopathological differences were noted in the specimens. All specimens showed varying degrees of vascular congestion, glandular atrophy, chronic inflammation, and mucosal metaplasia; the paclitaxel-impregnated stents were not consistently associated with more severe mucosal injury. Finally, mucosal ulceration was noted to be very rare in all specimens. This preliminary report describes the impact of paclitaxel-impregnated stents on sheep nasal mucosa, which tolerated these stents very well. Because paclitaxel minimizes scarring reactions at very low concentrations, paclitaxel-impregnated stents may prove useful in clinical situations in which frontal sinus stenting is deemed necessary. Additional investigations with animal models, as well as clinical trials, may be warranted.

Multi-channel gas-delivery system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rozenzon, Yan; Trujillo, Robert T.; Beese, Steven C.

One embodiment of the present invention provides a gas-delivery system for delivering reaction gas to a reactor chamber. The gas-delivery system includes a main gas-inlet port for receiving reaction gases and a gas-delivery plate that includes a plurality of gas channels. A gas channel includes a plurality of gas holes for allowing the reaction gases to enter the reactor chamber from the gas channel. The gas-delivery system further includes a plurality of sub-gas lines coupling together the main gas-inlet port and the gas-delivery plate, and a respective sub-gas line is configured to deliver a portion of the received reaction gasesmore » to a corresponding gas channel.« less

Surgical management of nasal obstruction.

PubMed

Moche, Jason A; Palmer, Orville

2012-05-01

The proper evaluation of the patient with nasal obstruction relies on a comprehensive history and physical examination. Once the site of obstruction is accurately identified, the patient may benefit from a trial of medical management. At times however, the definitive treatment of nasal obstruction relies on surgical management. Recognizing the nasal septum, nasal valve, and turbinates as possible sites of obstruction and addressing them accordingly can dramatically improve a patient's nasal breathing. Conservative resection of septal cartilage, submucous reduction of the inferior turbinate, and structural grafting of the nasal valve when appropriate will provide the optimal improvement in nasal airflow and allow for the most stable results. Copyright © 2012. Published by Elsevier Inc.

Snoring and Nasal Congestion

MedlinePlus

... treat the various causes of nasal congestion include: Topical nasal steroid spray Topical nasal antihistamine spray Oral antibiotic (in case of ... include more than just the decrease in oxygen levels at night during the apnea episodes. They also ...

Oral continuous positive airway pressure (CPAP) following nasal injury in a preterm infant.

PubMed

Carlisle, H R; Kamlin, C O F; Owen, L S; Davis, P G; Morley, C J

2010-03-01

Non-invasive respiratory support is increasingly popular but is associated with complications including nasal trauma. The present report describes a novel method of oral continuous positive airway pressure (CPAP) delivery in an extremely premature infant with severe nasal septum erosion. The distal end of a cut down endotracheal tube was passed through a small hole made in the teat of a dummy (infant pacifier) and sutured in place. The dummy was secured in the infant's mouth and CPAP was delivered to the pharynx. The device was well tolerated and the infant was successfully managed using this technique for 48 days, avoiding endotracheal intubation and ventilation.

Topical nasal decongestant oxymetazoline (0.05%) provides relief of nasal symptoms for 12 hours.

PubMed

Druce, H M; Ramsey, D L; Karnati, S; Carr, A N

2018-05-22

Nasal congestion, often referred to as stuffy nose or blocked nose is one of the most prevalent and bothersome symptoms of an upper respiratory tract infection. Oxymetazoline, a widely used intranasal decongestant, offers fast symptom relief, but little is known about the duration of effect. The results of 2 randomized, double-blind, vehicle-controlled, single-dose, parallel, clinical studies (Study 1, n=67; Study 2, n=61) in which the efficacy of an oxymetazoline (0.05% Oxy) nasal spray in patients with acute coryzal rhinitis was assessed over a 12-hour time-period. Data were collected on both subjective relief of nasal congestion (6-point nasal congestion scale) and objective measures of nasal patency (anterior rhinomanometry) in both studies. A pooled study analysis showed statistically significant changes from baseline in subjective nasal congestion for 0.05% oxymetazoline and vehicle at each hourly time-point from Hour 1 through Hour 12 (marginally significant at Hour 11). An objective measure of nasal flow was statistically significant at each time-point up to 12 hours. Adverse events on either treatment were infrequent. The number of subjects who achieved an improvement in subjective nasal congestion scores of at least 1.0 was significantly higher in the Oxy group vs. vehicle at all hourly time-points on a 6-point nasal congestion scale. This study shows for the first time, that oxymetazoline provides both statistically significant and clinically meaningful relief of nasal congestion and improves nasal airflow for up to 12 hours following a single dose.

Chronic Rhinosinusitis with Nasal Polyps

PubMed Central

Stevens, Whitney W.; Schleimer, Robert P.; Kern, Robert C.

2016-01-01

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an important clinical entity diagnosed by the presence of both subjective and objective evidence of chronic sinonasal inflammation. Symptoms include anterior or posterior rhinorrhea, nasal congestion, hyposmia and/or facial pressure or pain that last for greater than 12 weeks duration. Nasal polyps are inflammatory lesions that project into the nasal airway, are typically bilateral, and originate from the ethmoid sinus. Males are more likely to be affected than females but no specific genetic or environmental factors have been strongly linked to the development of this disorder to date. CRSwNP is frequently associated with asthma and allergic rhinitis but the cellular and molecular mechanisms that contribute to the clinical symptoms are not fully understood. Defects in the sinonasal epithelial cell barrier, increased exposure to pathogenic and colonized bacteria, and dysregulation of the host immune system are all thought to play prominent roles in disease pathogenesis. Additional studies are needed to further explore the clinical and pathophysiological features of CRSwNP so that biomarkers can be identified and novel advances can be made to improve the treatment and management of this disease. PMID:27393770

Evaluation of nasal IgA secretion in normal subjects by nasal spray and aspiration.

PubMed

Fujimoto, Chisa; Kido, Hiroshi; Sawabuchi, Takako; Mizuno, Dai; Hayama, Masaki; Yanagawa, Hiroaki; Takeda, Noriaki

2009-06-01

Nasal washing (NW) is a popular method for collecting human nasal lavage fluid. However, for NW the subject must be trained, and the method is unsuitable for field studies on untrained subjects. To overcome this problem, we have developed an easy and painless method, a nasal spray and aspiration (NSA) method. This method is different from NW in that the nasal cavity is misted over with saline, and the nasal lavage fluid is aspirated from the nostrils through a silicon tube. First, nasal lavage fluid was obtained twice by NSA with an interval of a week between lavages to evaluate intraindividual variability, and the IgA and protein levels in the nasal lavage fluid were measured by enzyme-linked immunosorbent assay and bicinchoninic acid assay, respectively. Next, the IgA value determined by NSA was compared with that by NW in another 12 normal subjects 2 days after NSA. In 10 normal subjects, mean volume of saline sprayed into the nose was 0.46+/-0.15 ml (mean+/-S.D.). Mean volume of aspirated nasal lavage fluid containing both sprayed saline and nasal secretion was 0.44+/-0.37 ml. The mean IgA level/mg protein in the nasal lavage fluid determined by NSA was 112+/-18 microg/mg protein at the first and 99+/-20 at the second times of measurement, being highly reproducible. The mean value by NSA was 114+/-19 microg/mg protein, being almost the same as that by NW of 99+/-27. These findings suggest that the IgA level/mg protein in nasal lavage fluid determined by NSA instead of NW might be useful for assessing the variability of nasal IgA secretion.

Perceiving nasal patency through mucosal cooling rather than air temperature or nasal resistance.

PubMed

Zhao, Kai; Blacker, Kara; Luo, Yuehao; Bryant, Bruce; Jiang, Jianbo

2011-01-01

Adequate perception of nasal airflow (i.e., nasal patency) is an important consideration for patients with nasal sinus diseases. The perception of a lack of nasal patency becomes the primary symptom that drives these patients to seek medical treatment. However, clinical assessment of nasal patency remains a challenge because we lack objective measurements that correlate well with what patients perceive. The current study examined factors that may influence perceived patency, including air temperature, humidity, mucosal cooling, nasal resistance, and trigeminal sensitivity. Forty-four healthy subjects rated nasal patency while sampling air from three facial exposure boxes that were ventilated with untreated room air, cold air, and dry air, respectively. In all conditions, air temperature and relative humidity inside each box were recorded with sensors connected to a computer. Nasal resistance and minimum airway cross-sectional area (MCA) were measured using rhinomanometry and acoustic rhinometry, respectively. General trigeminal sensitivity was assessed through lateralization thresholds to butanol. No significant correlation was found between perceived patency and nasal resistance or MCA. In contrast, air temperature, humidity, and butanol threshold combined significantly contributed to the ratings of patency, with mucosal cooling (heat loss) being the most heavily weighted predictor. Air humidity significantly influences perceived patency, suggesting that mucosal cooling rather than air temperature alone provides the trigeminal sensation that results in perception of patency. The dynamic cooling between the airstream and the mucosal wall may be quantified experimentally or computationally and could potentially lead to a new clinical evaluation tool.

Nasal Base Retraction: A Treatment Algorithm.

PubMed

Tas, Süleyman; Colakoglu, Salih; Lee, Bernard Travis

2017-06-01

Nasal base retraction results from cephalic malposition of the alar base in the vertical plane, which causes disharmony of the alar base with the rest of the nose structures. Correcting nasal base retraction is very important for improved aesthetic outcomes; however, there is a limited body of literature about this deformity and its treatment. Create a nasal base retraction treatment algorithm based on a severity classification system. This is a retrospective case review study of 53 patients who underwent rhinoplasty with correction of alar base retraction by the senior author (S.T.). The minimum follow-up time was 6 months. Levator labii alaque nasi muscle dissection or alar base release with or without a rim graft on the effected side were performed based on the severity of the alar base retraction. Aesthetic results were assessed with objective grading of preoperative and postoperative patient photographs by two independent plastic surgeons. Functional improvement was assessed with patient self-evaluations of nasal patency. Also, a rhinoplasty outcomes evaluation (ROE) questionnaire was distributed to patients. Comparison of preoperative and postoperative photographs demonstrated that nasal base asymmetry was significantly improved in all cases, and 85% of the patients had complete symmetry. Nasal obstruction was also significantly reduced after surgery (P < 0.001). The majority of patients reported satisfaction (92.5%), with an ROE total score greater than or equal to 20. New techniques and a treatment algorithm for correcting nasal base retraction deformities that will help rhinoplasty surgeons obtain aesthetically and functionally pleasing outcomes for patients. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Functional anatomy of the nasal bones and adjacent structures. Consequences for nasal surgery.

PubMed

Popko, M; Verlinde-Schellekens, S A M W; Huizing, E H; Bleys, R L A W

2018-03-01

The periosteum of the nasal bones, the periosteal-perichondrial nasal envelope, and the cartilaginous support of the bony vault were studied in serial coronal sections of four human cadaver noses. To differentiate between the various tissue components, the sections were stained according to Mallory-Cason and Verhoeff-Van Gieson stain. The results demonstrated: 1. the presence of clearly distinguishable layers of the periosteum covering the nasal bones; 2. the presence of a continuous periosteal-perichondrial covering of the bony and cartilaginous nasal vaults; 3. the way the cartilaginous support of the bony vault is constructed. The findings described in the present study may have clinical relevance in nasal surgery.

Comparison between Perceptual Assessments of Nasality and Nasalance Scores

ERIC Educational Resources Information Center

Brunnegard, Karin; Lohmander, Anette; van Doorn, Jan

2012-01-01

Background: There are different reports of the usefulness of the Nasometer[TM] as a complement to listening, often as correlation calculations between listening and nasalance measurements. Differences between findings have been attributed to listener experience and types of speech stimuli. Aims: To compare nasalance scores from the Nasometer with…

Novel application for electrochemotherapy: Immersion of nasal cavity in dog.

PubMed

Suzuki, Daniela O H; Berkenbrock, José A; de Oliveira, Krishna D; Freytag, Jennifer O; Rangel, Marcelo M M

2017-08-01

Electrochemotherapy is a new modality of local cancer treatment that increases the delivery of chemotherapy drugs into tumor cells by applying intense electric fields. This novel electrochemotherapy application was applied as an adjuvant to surgery and eliminated intranasal tumors in dog. The treatment challenges are the surgery limitations due to anatomy and residual tumor in the bone cavity. Most of the tumoral mass on nasal cavity was surgically removed. The internal nasal cavity was immersed in liquid and bleomycin before applying electric field. The solution was necessary to increase the superficial contact between plate electrodes and residual tumor. The numerical study demonstrated electrochemotherapy efficiency in different clinical situations. The proximity between electrodes and bone (<3 mm) and bone irregularities affect the electric field distribution on tumoral tissue. The tumoral tissue around bone protuberances tends to be eliminated. Electrochemotherapy with plate electrodes inside the cavity might not be effective. Different values of electric conductivity solution were studied; the ideal value was 0.5 S/m. The numerical and experimental results confirm the successful application of electrochemotherapy on dog nasal cavity. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Topical Drug Delivery in Chronic Rhinosinusitis Patients before and after Sinus Surgery Using Pulsating Aerosols

PubMed Central

Möller, Winfried; Schuschnig, Uwe; Celik, Gülnaz; Münzing, Wolfgang; Bartenstein, Peter; Häussinger, Karl; Kreyling, Wolfgang G.; Knoch, Martin

2013-01-01

Objectives Chronic rhinosinusitis (CRS) is a common chronic disease of the upper airways and has considerable impact on quality of life. Topical delivery of drugs to the paranasal sinuses is challenging, therefore the rate of surgery is high. This study investigates the delivery efficiency of a pulsating aerosol in comparison to a nasal pump spray to the sinuses and the nose in healthy volunteers and in CRS patients before and after sinus surgery. Methods 99mTc-DTPA pulsating aerosols were applied in eleven CRSsNP patients without nasal polyps before and after sinus surgery. In addition, pulsating aerosols were studied in comparison to nasal pump sprays in eleven healthy volunteers. Total nasal and frontal, maxillary and sphenoidal sinus aerosol deposition and lung penetration were assessed by anterior and lateral planar gamma camera imaging. Results In healthy volunteers nasal pump sprays resulted in 100% nasal, non-significant sinus and lung deposition, while pulsating aerosols resulted 61.3+/-8.6% nasal deposition and 38.7% exit the other nostril. 9.7+/-2.0 % of the nasal dose penetrated into maxillary and sphenoidal sinuses. In CRS patients, total nasal deposition was 56.7+/-13.3% and 46.7+/-12.7% before and after sinus surgery, respectively (p<0.01). Accordingly, maxillary and sphenoidal sinus deposition was 4.8+/-2.2% and 8.2+/-3.8% of the nasal dose (p<0.01). Neither in healthy volunteers nor in CRS patients there was significant dose in the frontal sinuses. Conclusion In contrast to nasal pump sprays, pulsating aerosols can deliver significant doses into posterior nasal spaces and paranasal sinuses, providing alternative therapy options before and after sinus surgery. Patients with chronic lung diseases based on clearance dysfunction may also benefit from pulsating aerosols, since these diseases also manifest in the upper airways. PMID:24040372

Perceiving Nasal Patency through Mucosal Cooling Rather than Air Temperature or Nasal Resistance

PubMed Central

Zhao, Kai; Blacker, Kara; Luo, Yuehao; Bryant, Bruce; Jiang, Jianbo

2011-01-01

Adequate perception of nasal airflow (i.e., nasal patency) is an important consideration for patients with nasal sinus diseases. The perception of a lack of nasal patency becomes the primary symptom that drives these patients to seek medical treatment. However, clinical assessment of nasal patency remains a challenge because we lack objective measurements that correlate well with what patients perceive.The current study examined factors that may influence perceived patency, including air temperature, humidity, mucosal cooling, nasal resistance, and trigeminal sensitivity. Forty-four healthy subjects rated nasal patency while sampling air from three facial exposure boxes that were ventilated with untreated room air, cold air, and dry air, respectively. In all conditions, air temperature and relative humidity inside each box were recorded with sensors connected to a computer. Nasal resistance and minimum airway cross-sectional area (MCA) were measured using rhinomanometry and acoustic rhinometry, respectively. General trigeminal sensitivity was assessed through lateralization thresholds to butanol. No significant correlation was found between perceived patency and nasal resistance or MCA. In contrast, air temperature, humidity, and butanol threshold combined significantly contributed to the ratings of patency, with mucosal cooling (heat loss) being the most heavily weighted predictor. Air humidity significantly influences perceived patency, suggesting that mucosal cooling rather than air temperature alone provides the trigeminal sensation that results in perception of patency. The dynamic cooling between the airstream and the mucosal wall may be quantified experimentally or computationally and could potentially lead to a new clinical evaluation tool. PMID:22022361

Physically facilitating drug-delivery systems

PubMed Central

Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

2012-01-01

Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

Comparison of Early-period Results of Nasal Splint and Merocel Nasal Packs in Septoplasty

PubMed Central

Bingöl, Fatih; Budak, Ali; Şimşek, Eda; Kılıç, Korhan; Bingöl, Buket Özel

2017-01-01

Objective Several types of nasal packs are used postoperatively in septoplasty. In this study, we compared two commonly used nasal packing materials, the intranasal septal splint with airway and Merocel tampon, in terms of pain, bleeding, nasal obstruction, eating difficulties, discomfort in sleep, and pain and bleeding during removal of packing in the early period. Methods The study group included 60 patients undergoing septoplasty. Patients were divided into two groups (n=30 in each group). An intranasal splint with airway was used for the patients in the first group after septoplasty, while Merocel nasal packing was used for the second group. Patients were investigated in terms of seven different factors - pain, bleeding while the tampon was in place, nasal obstruction, eating difficulties, night sleep, pain during removal of the nasal packing, and bleeding after removal of packing. Results There was no statistically significant difference between the groups in terms of pain 24 hours after operation (p=0.05), while visual analog scale (VAS) scores for nasal obstruction, night sleep, eating difficulties, and pain during packing removal were lower in the nasal splint group with a statistically significant difference (p<0.05). There was no statistically significant difference between the groups in terms of postoperative bleeding (p=0.23). Significantly less bleeding occurred during removal of the packing in the nasal splint group (p<0.05). Conclusion Our study indicates that the nasal splint was more comfortable and effective in terms of causing lesser bleeding and pain during removal of packing. PMID:29392071

Nasalance measures in Cantonese-speaking women.

PubMed

Whitehill, T L

2001-03-01

To establish and evaluate stimulus materials for nasalance measurement in Cantonese speakers, to provide normative data for Cantonese-speaking women, and to evaluate session-to-session reliability of nasalance measures. One hundred forty-one Cantonese-speaking women with normal resonance who were students in the Department of Speech and Hearing Sciences, University of Hong Kong. Participants read aloud four speech stimuli: oral sentences, nasal sentences, an oral paragraph (similar to the Zoo Passage), and an oral-nasal paragraph (similar to the Rainbow Passage). Data were collected and analyzed using the Kay Nasometer 6200. Data collection was repeated for a subgroup of speakers (n = 28) on a separate day. Nasalance materials were evaluated by using statistical tests of difference and correlation. Group mean (standard deviation) nasalance scores for oral sentences, nasal sentences, oral paragraph, and oral-nasal paragraph were 16.79 (5.99), 55.67 (7.38), 13.68 (7.16), and 35.46 (6.22), respectively. There was a significant difference in mean nasalance scores for oral versus nasal materials. Correlations between stimuli were as expected, ranging from 0.43 to 0.91. Session-to-session reliability was within 5 points for over 95% of speakers for the oral stimuli but for less than 76% of speakers for the nasal and oral-nasal stimuli. Standard nasalance materials have been developed for Cantonese, and normative data have been established for Cantonese women. Evaluation of materials indicated acceptable differentiation between oral and nasal materials. Two stimuli (nasal sentences and oral paragraph) are recommended for future use. Comparison with findings from other languages showed similarities in scores; possible language-specific differences are discussed. Session-to-session reliability was poorer for nasal than oral stimuli.

Nasal septal hematoma

MedlinePlus

... medlineplus.gov/ency/article/001292.htm Nasal septal hematoma To use the sharing features on this page, please enable JavaScript. A nasal septal hematoma is a collection of blood within the septum ...

Nasal hydropulsion.

PubMed

Elizabeth, Ashbaugh

2013-08-01

Intranasal tumors of dogs and cats pose a diagnostic and therapeutic challenge for the small animal practitioner. A simplified flushing technique to biopsy and debulk nasal tumors, that often results in immediate clinical relief for the patient is described. This technique can also be utilized to remove nasal foreign bodies. © 2013 Elsevier Inc. All rights reserved.

Ipratropium Nasal Spray

MedlinePlus

... follow these steps: Remove the clear plastic dust cap and the safety clip from the nasal spray ... the other nostril. Replace the clear plastic dust cap and safety clip. If the nasal tip becomes ...

Nasal fracture - aftercare

MedlinePlus

... page: //medlineplus.gov/ency/patientinstructions/000554.htm Nasal fracture - aftercare To use the sharing features on this ... that gives your nose its shape. A nasal fracture occurs when the bony part of your nose ...

Nasal Wash Treatment

MedlinePlus

... Guidelines Wash your hands. Make the nasal wash solution. Do not use tap water for the nasal ... Whichever water you use to make the saline solution, replace container or water at least weekly. To ...

Beclomethasone Nasal Spray

MedlinePlus

... the lining of the nose) after nasal polyp removal surgery. Beclomethasone nasal spray should not be used ... room temperature and away from excess heat and moisture (not in the bathroom).Unneeded medications should be ...

Nanotechnology for protein delivery: Overview and perspectives.

PubMed

Yu, Mikyung; Wu, Jun; Shi, Jinjun; Farokhzad, Omid C

2016-10-28

Protein-based therapeutics have made a significant impact in the treatment of a variety of important human diseases. However, given their intrinsically vulnerable structure and susceptibility to enzymatic degradation, many therapeutic proteins such as enzymes, growth factors, hormones, and cytokines suffer from poor physicochemical/biological stability and immunogenicity that may limit their potential benefits, and in some cases limit their utility. Furthermore, when protein therapeutics are developed for intracellular targets, their internalization and biological activity may be limited by inefficient membrane permeability and/or endosomal escape. Development of effective protein delivery strategies is therefore essential to further enhance therapeutic outcomes to enable widespread medical applications. This review discusses the advantages and limitations of marketed and developmental-stage protein delivery strategies, and provides a focused overview of recent advances in nanotechnology platforms for the systemic delivery of therapeutic proteins. In addition, we also highlight nanoparticle-mediated non-invasive administration approaches (e.g., oral, nasal, pulmonary, and transdermal routes) for protein delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Integrated delivery systems focus on service delivery after capitation efforts stall.

PubMed

2005-03-01

Integrated delivery systems focus on service delivery after capitation efforts stall. Integrated delivery systems are going through changes that are focusing the provider organizations more on delivering care than managing risk, says Dean C. Coddington, one of the leading researchers into capitated organizations and a senior consultant with McManis Consulting in Denver.

External Nasal Neuralgia: A Neuropathic Pain Within the Territory of the External Nasal Nerve.

PubMed

García-Moreno, Héctor; Aledo-Serrano, Ángel; Gimeno-Hernández, Jesús; Cuadrado, María-Luz

2015-10-01

Nasal pain is a challenging diagnosis and very little has been reported in the neurological literature. The nose is a sophisticated structure regarding its innervation, which is supplied by the first and second divisions of the trigeminal nerve. Painful cranial neuropathies are an important group in the differential diagnosis, although they have been described only scarcely. Here, we report a case that can conform a non-traumatic external nasal nerve neuralgia. A 76-year-old woman was referred to our office due to pain in her left nose. She was suffering from daily excruciating attacks, which were strictly limited to the territory supplied by her left external nasal nerve (left ala nasi and apex nasi). She denied previous traumatisms and the ancillary tests did not yield any underlying pathology. An anesthetic blockade of her left external nasal nerve achieved a marked reduction of the number of episodes as well as their intensity. External nasal neuralgia seems a specific neuralgia causing nasal pain. Anesthetic blockades of the external nasal nerve may be a valid treatment for this condition. © 2015 American Headache Society.

Does rhinoplasty improve nasal breathing?

PubMed

Xavier, Rui

2010-08-01

Rhinoplasty is a surgical procedure that aims to improve nasal aesthetics and nasal breathing. The aesthetic improvement of the nose is usually judged subjectively by the patient and the surgeon, but the degree of improvement of nasal obstruction is difficult to assess by clinical examination only. The measurement of peak nasal inspiratory flow (PNIF) is a reliable tool that has been shown to correlate with other objective methods of assessing nasal breathing and with patients' symptoms of nasal obstruction. Twenty-three consecutive patients undergoing rhinoplasty have been evaluated by measurement of PNIF before and after surgery. All but three patients had an increase in PNIF after surgery. The mean preoperative PNIF was 86.5 L/min and the mean postoperative PNIF was 123.0 L/min ( P < 0.001). Not surprisingly, the greatest improvement in PNIF was achieved when bilateral spreader grafts were used. This study suggests that rhinoplasty does improve nasal breathing. (c) Thieme Medical Publishers

Management of nasal septal perforation using silicone nasal septal button

PubMed Central

Mullace, M; Gorini, E; Sbrocca, M; Artesi, L; Mevio, N

2006-01-01

Summary Nasal septal perforation may present with various symptoms: epistaxis, crusting, secondary infection, whistling and nasal obstruction. Perforation may be treated by conservative pharmacological treatment or closed by surgical approach. A useful alternative is mechanical obturation, achieved inserting a prosthesis. The present report refers to a study on 15 patients (10 male, 5 female, mean age 38.5 years) treated by insertion of a one-piece or two-piece silicone septal button (Xomed). In the follow-up period, insertion of the nasal button reduced epistaxis, eliminated whistling during inspiration, and reduced nasal obstruction and crusting around the margin of the perforation. Contraindications are presence of acute infection with osteitis, chronic septal disease (Wegener), neoplasia and extremely large perforations. The latest buttons appear to be superior to the conventional type on account of plasticity and adaptability which offer greater conformity to the septum. This study also reveals that the new septal button is well tolerated by patients. PMID:18236638

Complications of Nasal Bone Fractures.

PubMed

Hwang, Kun; Yeom, Seung Han; Hwang, Suk Hyun

2017-05-01

The aim of this study was to perform a systematic review of the treatment of nasal bone fractures. The search terms ("nasal bone fracture" AND complication) and ("nasal bone fracture" AND [anosmia OR olfaction OR olfactory nerve OR smell]) and (anosmia AND ["nasal preparation" OR "nasal antiseptics"]) were used to search PubMed and SCOPUS. Of the 500 titles, 40 full papers were reviewed. One paper was excluded, and 3 mined papers were added. Ultimately, 12 papers were analyzed. The overall deformity rate was 10.4% ± 4.8%. No significant differences were found between patients who underwent closed reduction (14.7% ± 7.3%) and those who underwent open reduction (9.4% ± 4.4%), between those who underwent local anesthesia (5.8% ± 4.5%), and those who underwent general anesthesia (8.8% ± 3.8%), or between those who received timely treatment (5.7%) and those whose treatment was delayed (9.0%). Septal deviation occurred in 10.0% of patients as a sequela of nasal bone fracture. The nasal obstruction rate was 10.5% ± 5.3%. Fewer patients of nasal obstruction occurred in the open reduction patients (6.9% ± 4.4%) than in the closed reduction patients (15.2%). One patient of epiphora and 1 patient of diplopia were reportedAmong the 77 patients with nasal bone fractures, 29 (37.7% ± 11.3%) complained of olfactory disturbances. No significant associations were found between the type of fracture and the presence of olfactory disturbances. It is recommended for providers to explain to patients that approximately one-tenth of nasal bone fractures exhibit deformity, septal deviation, or nasal obstruction after surgery. Surgeons should take considerable care to avoid the olfactory mucosa during reduction surgery.

Changes in nasal airflow and heat transfer correlate with symptom improvement after surgery for nasal obstruction.

PubMed

Kimbell, J S; Frank, D O; Laud, Purushottam; Garcia, G J M; Rhee, J S

2013-10-18

Surgeries to correct nasal airway obstruction (NAO) often have less than desirable outcomes, partly due to the absence of an objective tool to select the most appropriate surgical approach for each patient. Computational fluid dynamics (CFD) models can be used to investigate nasal airflow, but variables need to be identified that can detect surgical changes and correlate with patient symptoms. CFD models were constructed from pre- and post-surgery computed tomography scans for 10 NAO patients showing no evidence of nasal cycling. Steady-state inspiratory airflow, nasal resistance, wall shear stress, and heat flux were computed for the main nasal cavity from nostrils to posterior nasal septum both bilaterally and unilaterally. Paired t-tests indicated that all CFD variables were significantly changed by surgery when calculated on the most obstructed side, and that airflow, nasal resistance, and heat flux were significantly changed bilaterally as well. Moderate linear correlations with patient-reported symptoms were found for airflow, heat flux, unilateral allocation of airflow, and unilateral nasal resistance as a fraction of bilateral nasal resistance when calculated on the most obstructed nasal side, suggesting that these variables may be useful for evaluating the efficacy of nasal surgery objectively. Similarity in the strengths of these correlations suggests that patient-reported symptoms may represent a constellation of effects and that these variables should be tracked concurrently during future virtual surgery planning. © 2013 Elsevier Ltd. All rights reserved.

Effect of Deviated Nasal Septum Type on Nasal Mucociliary Clearance, Olfactory Function, Quality of Life, and Efficiency of Nasal Surgery.

PubMed

Berkiten, Güler; Kumral, Tolgar Lütfi; Saltürk, Ziya; Atar, Yavuz; Yildirim, Güven; Uyar, Yavuz; Aydoğdu, Imran; Arslanoğlu, Ahmet

2016-07-01

The aim of this study was to analyze the influence of deviated nasal septum (DNS) type on nasal mucociliary clearance, quality of life (QoL), olfactory function, and efficiency of nasal surgery (septoplasty with or without inferior turbinate reduction and partial middle turbinectomy). Fifty patients (20 females and 30 males) with septal deviation were included in the study and were divided into 6 groups according to deviation type after examination by nasal endoscopy and paranasal computed tomography. The saccharin clearance test to evaluate the nasal mucociliary clearance time, Connecticut Chemosensory Clinical Research Center smell test for olfactory function, and sinonasal outcome test-22 (SNOT-22) for patient satisfaction were applied preoperatively and postoperatively at the sixth week after surgery. Nasal mucociliary clearance, smell, and SNOT-22 scores were measured before surgery and at the sixth week following surgery. No significant difference was found in olfactory and SNOT-22 scores for any of the DNS types (both convex and concave sides) (P > 0.05). In addition, there was no difference in the saccharin clearance time (SCT) of the concave and convex sides (P > 0.05). According to the DNS type, the mean SCT of the convex sides showed no difference, but that of the concave sides showed a difference in types 3, 4, 5, and 6. These types had a prolonged SCT (P < 0.05). Olfactory scores revealed no difference postoperatively in types 5 and 6 but were decreased significantly in types 1 to 4 (P < 0.05). There was no significant difference in the healing of both the mucociliary clearance (MCC) and olfactory functions. SNOT-22 results showed a significant decrease in type 3. All DNS types disturb the QoL regarding nasal MCC and olfaction functions. MCC values, olfactory function, and QoL scores are similar among the DNS types. Both sides of the DNS types affect the MCC scores symmetrically. Septal surgery improves olfaction function and QoL at the

Intranasal hydrocodone-acetaminophen abuse induced necrosis of the nasal cavity and pharynx.

PubMed

Alexander, David; Alexander, Keith; Valentino, Joseph

2012-11-01

Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid transmucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Retrospective chart review. Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. The majority of patients will initially deny the behavior, frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow-up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented, with one resulting in death. The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue, which can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Cosmetic and Functional Nasal Deformities

MedlinePlus

... nasal complaints. Nasal deformity can be categorized as “cosmetic” or “functional.” Cosmetic deformity of the nose results in a less ... taste , nose bleeds and/or recurrent sinusitis . A cosmetic or functional nasal deformity may occur secondary to ...

Cosmetic rostral nasal reconstruction after nasal planum and premaxilla resection: technique and results in two dogs.

PubMed

Gallegos, Javier; Schmiedt, Chad W; McAnulty, Jonathan F

2007-10-01

To describe a novel reconstructive technique after nasal planum and premaxilla resection. Case report. Dogs (n=2) with squamous cell carcinoma (SCC) of the nasal planum. A 9-year-old neutered female Labrador retriever (dog 1) and an 11-year-old neutered male Golden retriever (dog 2) had resection of the nasal planum and premaxilla for treatment of locally invasive SCC. Reconstruction of a nasal planum facsimile was based on use of the nonhaired pigmented margins of bilateral labial mucocutaneous rotation-advancement flaps. Reconstruction of the premaxilla by construction of a nasal planum facsimile resulted in uncomplicated wound healing and improved cosmesis. There was no tumor recurrence at 1290 (dog 1) and 210 (dog 2) days after surgery. Reconstruction of a nasal planum facsimile was successfully performed without complications in 2 dogs with high owner satisfaction with cosmetic appearance. This technique represents a significant advancement in surgical cosmetic outcome, may potentially reduce postoperative complications, and should be considered for dogs requiring nasal reconstruction after nasal planum resection with premaxillectomy.

Nose-to-brain drug delivery by nanoparticles in the treatment of neurological disorders.

PubMed

Ong, Wei-Yi; Shalini, Suku-Maran; Costantino, Luca

2014-01-01

Many potential drugs for the treatment of neurological diseases are unable to reach the brain in sufficient enough concentrations to be therapeutic because of the blood brain barrier. On the other hand, direct delivery of drugs to the brain provides the possibility of a greater therapeutic-toxic ratio than with systemic drug delivery. The use of intranasal delivery of therapeutic agents to the brain provides a means of bypassing the blood brain barrier in a non-invasive manner. In this respect, nanosized drug carriers were shown to enhance the delivery of drugs to CNS compared to equivalent drug solution formulations. Neurological conditions that have been studied in animal models that could benefit from nose-to-brain delivery of nanotherapeutics include pain, epilepsy, neurodegenerative disease and infectious diseases. The delivery of drugs to the brain via the nose-to-brain route holds great promise, on the basis of preclinical research by means of drug delivery systems such as polymeric nanoparticles and clinical data related to intranasal delivery to CNS of large molecular weight biologics administered in solution, but safety issues about toxicity on nasal mucosa, Np transport into the brain, delivery only to specific brain regions and variability in the adsorbed dose still represent research topics that need to be considered, with a view of clinical translation of these delivery systems.

CPAP and High-Flow Nasal Cannula Oxygen in Bronchiolitis.

PubMed

Sinha, Ian P; McBride, Antonia K S; Smith, Rachel; Fernandes, Ricardo M

2015-09-01

Severe respiratory failure develops in some infants with bronchiolitis because of a complex pathophysiologic process involving increased airways resistance, alveolar atelectasis, muscle fatigue, and hypoxemia due to mismatch between ventilation and perfusion. Nasal CPAP and high-flow nasal cannula (HFNC) oxygen may improve the work of breathing and oxygenation. Although the mechanisms behind these noninvasive modalities of respiratory support are not well understood, they may help infants by way of distending pressure and delivery of high concentrations of warmed and humidified oxygen. Observational studies of varying quality have suggested that CPAP and HFNC may confer direct physiologic benefits to infants with bronchiolitis and that their use has reduced the need for intubation. No trials to our knowledge, however, have compared CPAP with HFNC in bronchiolitis. Two randomized trials compared CPAP with oxygen delivered by low-flow nasal cannula or face mask and found some improvements in blood gas results and some physiologic parameters, but these trials were unable to demonstrate a reduction in the need for intubation. Two trials evaluated HFNC in bronchiolitis (one comparing it with headbox oxygen, the other with nebulized hypertonic saline), with the results not seeming to suggest important clinical or physiologic benefits. In this article, we review the pathophysiology of respiratory failure in bronchiolitis, discuss these trials in detail, and consider how future research studies may be designed to best evaluate CPAP and HFNC in bronchiolitis.

Calcium silicate-based drug delivery systems.

PubMed

Zhu, Ying-Jie; Guo, Xiao-Xuan; Sham, Tsun-Kong

2017-02-01

Compared with other inorganic materials such as silica, metal oxides, noble metals and carbon, calcium silicate-based materials, especially nanostructured calcium silicate materials, have high biocompatibility, bioactivity and biodegradability, high specific surface area, nanoporous/hollow structure, high drug-loading capacity, pH-responsive drug release behavior and desirable drug release properties, and thus they are promising for the application in drug delivery. Calcium silicate-based drug delivery systems have a long drug-release time, which can significantly prolong the therapeutic effect of drugs. Another advantage of calcium silicate-based drug delivery systems is their pH-responsive drug release property, which can act as an ideal platform for targeted drug delivery. Areas covered: In recent years, studies have been carried out on calcium silicate-based drug delivery systems, and important results and insights have been documented. This article is not intended to offer a comprehensive review on the research on calcium silicate-based drug delivery systems, but presents some examples reported in the literature, and includes new insights obtained by tracking the interactions between drug molecules and calcium silicate carriers on the molecular level using the synchrotron-based X-ray spectroscopy. Expert opinion: Finally, our opinions on calcium silicate-based drug delivery systems are provided, and several research directions for the future studies are proposed.

Risk factors for nasal malignancies in German men: the South-German Nasal cancer study.

PubMed

Greiser, Eberhard M; Greiser, Karin Halina; Ahrens, Wolfgang; Hagen, Rudolf; Lazszig, Roland; Maier, Heinz; Schick, Bernhard; Zenner, Hans Peter

2012-11-06

There are few studies of the effects of nasal snuff and environmental factors on the risk of nasal cancer. This study aimed to investigate the impact of using nasal snuff and of other risk factors on the risk of nasal cancer in German men. A population-based case-control study was conducted in the German Federal States of Bavaria and Baden-Württemberg. Tumor registries and ear, nose and throat departments provided access to patients born in 1926 or later. Telephone interviews were conducted with 427 cases (mean age 62.1 years) and 2.401 population-based controls (mean age 60.8 years). Ever-use of nasal snuff was associated with an odds ratio (OR) for nasal cancer of 1.45 (95% confidence interval [CI] 0.88-2.38) in the total study population, whereas OR in smokers was 2.01 (95% CI 1.00-4.02) and in never smokers was 1.10 (95% CI 0.43-2.80). The OR in ever-smokers vs. never-smokers was 1.60 (95% CI 1.24-2.07), with an OR of 1.06 (95% CI 1.05-1.07) per pack-year smoked, and the risk was significantly decreased after quitting smoking. Exposure to hardwood dust for at least 1 year resulted in an OR of 2.33 (95% CI 1.40-3.91) in the total population, which was further increased in never-smokers (OR 4.89, 95% CI 1.92-12.49) in analyses stratified by smoking status. The OR for nasal cancer after exposure to organic solvents for at least 1 year was 1.53 (1.17-2.01). Ever-use of nasal sprays/nasal lavage for at least 1 month rendered an OR of 1.59 (1.04-2.44). The OR after use of insecticides in homes was 1.48 (95% CI 1.04-2.11). Smoking and exposure to hardwood dust were confirmed as risk factors for nasal carcinoma. There is evidence that exposure to organic solvents, and in-house use of insecticides could represent novel risk factors. Exposure to asbestos and use of nasal snuff were risk factors in smokers only.

Nasal obstruction and human communication.

PubMed

Malinoff, R; Moreno, C

1989-04-01

Nasal obstruction may cause a variety of communication disorders, particularly in children. The effects of nasal obstruction on hearing, speech, language, and voice are examined. Methods for assessing the effects of nasal obstruction are delineated, and recommendations for therapeutic interventions are described.

Polymers for Drug Delivery Systems

PubMed Central

Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

2012-01-01

Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

Nasal masks or binasal prongs for delivering continuous positive airway pressure in preterm neonates-a randomised trial.

PubMed

Chandrasekaran, Aparna; Thukral, Anu; Jeeva Sankar, M; Agarwal, Ramesh; Paul, Vinod K; Deorari, Ashok K

2017-03-01

The objective of this study was to compare the efficacy and safety of continuous positive airway pressure (CPAP) delivered using nasal masks with binasal prongs. We randomly allocated 72 neonates between 26 and 32 weeks gestation to receive bubble CPAP by either nasal mask (n = 37) or short binasal prongs (n = 35). Primary outcome was mean FiO 2 requirement at 6, 12 and 24 h of CPAP initiation and the area under curve (AUC) of FiO 2 against time during the first 24 h (FiO 2 AUC 0-24 ). Secondary outcomes were the incidence of CPAP failure and nasal trauma. FiO 2 requirement at 6, 12 and 24 h (mean (SD); 25 (5.8) vs. 27.9 (8); 23.8 (4.5) vs. 25.4 (6.8) and 22.6 (6.8) vs. 22.7 (3.3)) as well as FiO 2 AUC 0-24 (584.0 (117.8) vs. 610.6 (123.6)) were similar between the groups. There was no difference in the incidence of CPAP failure (14 vs. 20%; relative risk 0.67; 95% confidence interval 0.24-1.93). Incidence of severe nasal trauma was lower with the use of nasal masks (0 vs. 31%; p < .001). Nasal masks appear to be as efficacious as binasal prongs in providing CPAP. Masks are associated with lower risk of severe nasal trauma. CTRI2012/08/002868 What is Known? • Binasal prongs are better than single nasal and nasopharyngeal prongs for delivering continuous positive airway pressure (CPAP) in preventing need for re-intubation. • It is unclear if they are superior to newer generation nasal masks in preterm neonates requiring CPAP. What is New? • Oxygen requirement during the first 24 h of CPAP delivery is comparable with use of nasal masks and binasal prongs. • Use of nasal masks is, however, associated with significantly lower risk of severe grades of nasal injury.

Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin.

PubMed

Cai, Zheng; Song, Xiangrong; Sun, Feng; Yang, Zhaoxiang; Hou, Shixiang; Liu, Zhongqiu

2011-12-01

Gastrodin is the major bioactive constituent of the traditional Chinese drug "Tianma." It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.

21 CFR 874.3900 - Nasal dilator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... nasal airflow. The device decreases airway resistance and increases nasal airflow. The external nasal...

21 CFR 874.3900 - Nasal dilator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... nasal airflow. The device decreases airway resistance and increases nasal airflow. The external nasal...

Efficient Nose-to-Lung (N2L) Aerosol Delivery with a Dry Powder Inhaler

PubMed Central

Golshahi, Laleh; Behara, Srinivas R.B.; Tian, Geng; Farkas, Dale R.; Hindle, Michael

2015-01-01

Abstract Purpose: Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy. Methods: The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region. Results: The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5–2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%. Conclusions: The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy. PMID:25192072

A Systems Approach to Nitrogen Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goins, Bobby

A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should bemore » less frustration associated with the delivery process.« less

Fiber coupled optical spark delivery system

DOEpatents

Yalin, Azer; Willson, Bryan; Defoort, Morgan

2008-08-12

A spark delivery system for generating a spark using a laser beam is provided, the spark delivery system including a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. In addition, the laser delivery assembly includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. In accordance with embodiments of the present invention, the assembly may be used to create a spark in a combustion engine. In accordance with other embodiments of the present invention, a method of using the spark delivery system is provided. In addition, a method of choosing an appropriate fiber for creating a spark using a laser beam is also presented.

The effects of systemic, topical, and intralesional steroid treatments on apoptosis level of nasal polyps.

PubMed

Kapucu, Burak; Cekin, Engin; Erkul, Bulent Evren; Cincik, Hakan; Gungor, Atila; Berber, Ufuk

2012-09-01

The purpose of this study was to compare the apoptotic responses to systemic, topical, and intrapolyp injection of glucocorticoid with no treatment in nasal polyps. Prospective, randomized controlled study. Tertiary training hospital. The study was performed on 48 patients with nasal polyposis in the Department of Otorhinolaryngology between 2008 and 2009. Patients were assigned to 1 of 4 groups of 12 patients. Group A was treated with oral methylprednisolone 1 mg/kg/d, and the dose was tapered gradually. Group B received 0.3 mL triamcinolone acetonide (40 mg/mL), which was injected into polyp tissue. Group C was treated with topical 55 µg triamcinolone acetonide 2 times daily for 1 month. Group D received no medication. Samples were collected endoscopically after the seventh day for groups A and B, the first month for group C, and the first visit for group D. Apoptotic indexes were determined using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. Statistically significant differences in apoptotic index were found between each steroid-medicated group and the control group (P (D-A) = .0001; P (D-B) = .003; P (D-C) = .026) and between groups A and C (P (A-C) = .012). Group B did not differ significantly from either group A or C (P (A-B) = .11; P (B-C) = .75). The apoptotic index in nasal polyps treated with systemic, topical, and intrapolyp injection forms of glucocorticoids was higher than that in the control group. Systemic steroid treatment induced the most apoptosis.

Sterile Product Packaging and Delivery Systems.

PubMed

Akers, Michael J

2015-01-01

Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology.

Recent developments in protein and peptide parenteral delivery approaches

PubMed Central

Patel, Ashaben; Cholkar, Kishore; Mitra, Ashim K

2014-01-01

Discovery of insulin in the early 1900s initiated the research and development to improve the means of therapeutic protein delivery in patients. In the past decade, great emphasis has been placed on bringing protein and peptide therapeutics to market. Despite tremendous efforts, parenteral delivery still remains the major mode of administration for protein and peptide therapeutics. Other routes such as oral, nasal, pulmonary and buccal are considered more opportunistic rather than routine application. Improving biological half-life, stability and therapeutic efficacy is central to protein and peptide delivery. Several approaches have been tried in the past to improve protein and peptide in vitro/in vivo stability and performance. Approaches may be broadly categorized as chemical modification and colloidal delivery systems. In this review we have discussed various chemical approaches such as PEGylation, hyperglycosylation, mannosylation, and colloidal carriers including microparticles, nanoparticles, liposomes, carbon nanotubes and micelles for improving protein and peptide delivery. Recent developments on in situ thermosensitive gel-based protein and peptide delivery have also been described. This review summarizes recent developments on some currently existing approaches to improve stability, bioavailability and bioactivity of peptide and protein therapeutics following parenteral administration. PMID:24592957

[Nasal septal abscess].

PubMed

Barril, María F; Ferolla, Fausto M; José, Pablo; Echave, Cecilia; Tomezzoli, Silvana; Fiorini, Sandra; López, Eduardo Luis

2008-12-01

A nasal septal abscess (NA) is defined as a collection of pus between the cartilage or bony septum and its normally applied mucoperichondrium or mucoperiostium. It is an uncommon disease which should be suspected in a patient with acute onset of nasal obstruction and recent history of nasal trauma, periodontal infection or an inflammatory process of the rhinosinusal region. We report a case of an 8-year-old boy with bilateral NA caused by community-acquired methicillin-resistant Staphylococcus aureus(MR-CO) in order to emphasize the importance of prompt diagnosis and adequate treatment to prevent the potentially dangerous spread of infection and the development of severe functional and cosmetic sequelae.

Chondrosarcoma of the nasal septum: A case report.

PubMed

Kainuma, Kazuyuki; Netsu, Kiminori; Asamura, Kenji; Hayashi, Keiko; Takumi, Yutaka; Ota, Hiroyoshi; Usami, Shin-ichi

2009-10-01

Chondrosarcoma make up only 10-20% of malignant primary bone tumors, with 5-10% located in the head and neck (Downey TJ, Clark SK, Moore DW. Chondrosarcoma of the nasal septum. Otolaryngol Head Neck Surg 2001;125:98-100), and nasal septal chondrosarcoma is extremely rare. Surgical excision is the only curative treatment and radiation and chemotherapy have a limited role for palliation. We used a navigation system in endoscopic surgery without complications for a case of chondrosarcoma of the nasal septum by means of a midfacial degloving approach at primary operation and an external incision approach at salvage operation for local recurrence. To our knowledge, this is the first report of the use of such a system for this surgical approach along with a salvage operation. We discuss the clinical presentation, diagnosis, and treatment of this case as well as present a review of the literature.

Analytical challenges and regulatory requirements for nasal drug products in europe and the u.s.

PubMed

Trows, Sabrina; Wuchner, Klaus; Spycher, Rene; Steckel, Hartwig

2014-04-11

Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results.

Pharmacokinetics of a new, nasal formulation of naloxone.

PubMed

Tylleskar, Ida; Skulberg, Arne Kristian; Nilsen, Turid; Skarra, Sissel; Jansook, Phatsawee; Dale, Ola

2017-05-01

Nasal naloxone is wanted for bystander administration in opioid overdose and as a needle-free alternative for emergency medical personnel. Epidemiologic studies have indicated a therapeutic effect of bystander administration of low-concentration/high-volume formulations. The objective for this study was to describe the nasal pharmacokinetics of a new high-concentration/low-volume nasal formulation of naloxone. This was an open, randomized triple crossover trial in healthy, human volunteers (n = 12) where two doses of nasal naloxone (0.8 and 1.6 mg) and one intravenous dose (1.0 mg) were compared. Fifteen serum samples were collected before and until 6 h after naloxone administration. Quantification of naloxone was performed by a validated liquid chromatography-tandem mass spectrometry method. Bioavailability was 0.54 (0.45-0.63) for the 0.8 mg and 0.52 (0.37-0.67) for the 1.6 mg nasal naloxone formulation. Maximum concentration levels (C max ) were 1.45 ng/ml (1.07-1.84) for 0.8 mg and 2.57 ng/ml (1.49-3.66) for the 1.6 mg. Time to maximum concentrations (T max ) were reached at 17.9 min (11.4-24.5) and 18.6 min (14.4-22.9) for the 0.8 mg and the 1.6 mg doses, respectively. This nasal naloxone formulation had a rapid, systemic uptake and higher bioavailability than naloxone formulations not designed for IN use. This indicates that an optimized high-concentration/low-volume nasal spray formulation may deliver a therapeutic dose. The 1.6 mg nasal dose provided serum concentrations that surpassed those of 1.0 mg IV after 15-20 min and stayed above for the rest of the study period.

Nasal Glial Heterotopia with Cleft Palate.

PubMed

Chandna, Sudhir; Mehta, Milind A; Kulkarni, Abhishek Kishore

2018-01-01

Congenital midline nasal masses are rare anomalies of which nasal glial heterotopia represents an even rarer subset. We report a case of a 25-day-old male child with nasal glial heterotopia along with cleft palate suggesting embryonic fusion anomaly which was treated with excision and primary closure for nasal mass followed by palatal repair at later date.

Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

PubMed Central

Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

2012-01-01

This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

Designing and assessing a sustainable networked delivery (SND) system: hybrid business-to-consumer book delivery case study.

PubMed

Kim, Junbeum; Xu, Ming; Kahhat, Ramzy; Allenby, Braden; Williams, Eric

2009-01-01

We attempted to design and assess an example of a sustainable networked delivery (SND) system: a hybrid business-to-consumer book delivery system. This system is intended to reduce costs, achieve significant reductions in energy consumption, and reduce environmental emissions of critical local pollutants and greenhouse gases. The energy consumption and concomitant emissions of this delivery system compared with existing alternative delivery systems were estimated. We found that regarding energy consumption, an emerging hybrid delivery system which is a sustainable networked delivery system (SND) would consume 47 and 7 times less than the traditional networked delivery system (TND) and e-commerce networked delivery system (END). Regarding concomitant emissions, in the case of CO2, the SND system produced 32 and 7 times fewer emissions than the TND and END systems. Also the SND system offer meaningful economic benefit such as the costs of delivery and packaging, to the online retailer, grocery, and consumer. Our research results show that the SND system has a lot of possibilities to save local transportation energy consumption and delivery costs, and reduce environmental emissions in delivery system.

[Hemangiopericytoma in nasal cavity: a case report].

PubMed

Hu, Honghai; Shi, Qifeng; Chen, Jidong

2015-05-01

We report a case of a 46 year old female patient with nasal hemangiopericytoma. She complained of left nasal congestion, pus snot for 10 years, sometimes with left nasal bleeding. Physical examination: in the left nasal tract saw red soft neoplasm, roughness surface, easy bleeding when touched. Sinus CT shows: bilateral maxillary sinus, ethmoid sinus, sphenoid sinus and the left posterior nasal cavity lesions, considering inflammation with the formation of polyps, tumor not excluded. The left nasal cavity neoplasm biopsy shows: hemangioma of left nasal cavity. After admission in general anesthesia, we do transnasal endoscopic sinus openning operation and the left nasal cavity neoplasm resection. Postoperative pathological examination shows: the left nasal cavity hemangiopericytoma. Immunohistochemical showed: Vimentin(+), Smooth muscle actin(+), Desmin(-), endothelial cells CD31(-) and CD34(-). No postoperative radiotherapy or chemotherapy, no tumor recurrence. After one year of follow-up, the contact was lost.

Mask versus Nasal Tube for Stabilization of Preterm Infants at Birth: Respiratory Function Measurements.

PubMed

van Vonderen, Jeroen J; Kamlin, C Omar; Dawson, Jennifer A; Walther, Frans J; Davis, Peter G; te Pas, Arjan B

2015-07-01

To compare the nasal tube with face mask as interfaces for stabilization of very preterm infants at birth by using physiological measurements of leak, obstruction, and expired tidal volumes during positive pressure ventilation (PPV). In the delivery room, 43 infants <30 weeks gestation were allocated to receive respiratory support by nasal tube or face mask. Respiratory function, heart rate, and oxygen saturation were measured. Occurrence of obstruction, amount of leak, and tidal volumes were compared using a Mann-Whitney U test or a Fisher exact test. The first 5 minutes after initiation of PPV were analyzed (1566 inflations in the nasal tube group and 1896 inflations in the face mask group). Spontaneous breathing coincided with PPV in 32% of nasal tube and 34% of face mask inflations. During inflations, higher leak was observed using nasal tube compared with face mask (98% [33%-100%] vs 14 [0%-39%]; P < .0001). Obstruction occurred more often (8.2% vs 1.1%; P < .0001). Expired tidal volumes were significantly lower during inflations when using nasal tube compared with face mask (0.0 [0.0-3.1] vs 9.9 [5.5-12.8] mL/kg; P < .0001) and when spontaneous breathing coincided with PPV (4.4 [2.1-8.4] vs 9.6 [5.4-15.2] mL/kg; P < .0001) but were similar during breathing on continuous positive airway pressure (4.7 [2.8-6.9] vs 4.8 [2.7-7.9] mL/kg; P > 0.05). Heart rate was not significantly different between groups, but oxygen saturation was significantly lower in the nasal tube group the first 2 minutes after start of respiratory support. The use of a nasal tube led to large leak, more obstruction, and inadequate tidal volumes compared with face mask. Trial registration Registered with the Dutch Trial Registry (NTR 2061) and the Australia and New Zealand Clinical Trials Register (ACTRN 12610000230055). Copyright © 2015 Elsevier Inc. All rights reserved.

Objective measurements for grading the nasal esthetics on Basal view in individuals with secondary cleft nasal deformity.

PubMed

He, Xing; Li, Hua; Shao, Yan; Shi, Bing

2015-01-01

The purpose of this study is to ascertain objective nasal measurements from the basal view that are predictive of nasal esthetics in individuals with secondary cleft nasal deformity. Thirty-three patients who had undergone unilateral cleft lip repair were retrospectively reviewed in this study. The degree of nasal deformity was subjectively ranked by seven surgeons using standardized basal-view measurements. Nine physical objective parameters including angles and ratios were measured. Correlations and regressions between these objective and subjective measurements were then analyzed. There was high concordance in subjective measurements by different surgeons (Kendall's harmonious coefficient = W = .825, P = .006). The strongest predictive factors for nasal aesthetics were the ratio of length of nasal alar (r = .370, P = .034) and the degree of deviation of the columnar axis (r = .451, P = .008). The columellar angle had a more powerful effect in rating nasal esthetics. There was reliable concordance in subjective ranking of nasal esthetics by surgeons. Measurement of the columnar angle may serve as an independent, objective predictor of esthetics of the nose.

Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

PubMed

Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled

2016-01-01

Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems.

Comparison between a Single-Channel Nasal Airflow Device and Oximetry for the Diagnosis of Obstructive Sleep Apnea

PubMed Central

Rofail, Lydia Makarie; Wong, Keith K.H.; Unger, Gunnar; Marks, Guy B.; Grunstein, Ronald R.

2010-01-01

Rationale: The most common single channel devices used for obstructive sleep apnea (OSA) screening are nasal airflow and oximetry. No studies have directly compared their role in diagnosing OSA at home. Study Objectives: To prospectively compare the diagnostic utility of home-based nasal airflow and oximetry to attended polysomnography (PSG) and to assess the diagnostic value of adding oximetry to nasal airflow for OSA. Design: Cross-sectional study Setting: Laboratory and home Participants: Sleep clinic patients with suspected OSA. Interventions: All patients had laboratory PSG and 2 sets of 3 consecutive nights on each device; nasal airflow (Flow Wizard, DiagnoseIT, Australia) and oximetry (Radical Set, Masimo, USA) at home in random order. Results: Ninety-eight of the 105 patients enrolled completed home monitoring. The accuracy of nasal airflow respiratory disturbance index (NF RDI) was not different from oximetry (ODI 3%) for diagnosing OSA (area under the ROC curve (AUC) difference, 0.04; 95% CI of difference −0.05 to 0.12; P = 0.43) over 3 nights of at-home recording. The accuracy of NF RDI was higher after 3 nights compared to one night (AUC difference, 0.05; 95% CI of difference, 0.01 to 0.08; P = 0.04). Addition of oximetry to nasal airflow did not increase the accuracy for predicting OSA compared to nasal airflow alone (P > 0.1). Conclusions: Nasal flow and oximetry have equivalent accuracy for diagnosing OSA in the home setting. Choice of device for home screening of sleep apnea may depend on logistical and service delivery issues. Citation: Makarie Rofail L; Wong KKH; Unger G; Marks GB; Grunstein RR. Comparison between a single-channel nasal airflow device and oximetry for the diagnosis of obstructive sleep apnea. SLEEP 2010;33(8):1106-1114. PMID:20815194

Intranasal Hydrocodone-Acetaminophen Abuse Induced Necrosis of the Nasal Cavity and Pharynx

PubMed Central

Alexander, David; Alexander, Keith; Valentino, Joseph

2012-01-01

Objectives Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid trans mucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. Study Design Retrospective chart review. Methods Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. Results The majority of patients will initially deny the behavior frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented with one resulting in death. Conclusions The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue that can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene. Study Design Chart review, level of evidence: 4 PMID:22965281

Actual therapeutic management of allergic and hyperreactive nasal disorders

PubMed Central

Rudack, Claudia

2004-01-01

Allergic rhinitis (AR) and hyperractive disorders of the upper airways, depending upon the type of releasing stimuli, are defined as nasal hyperreactivity, for example in the case of AR, or as non-specific nasal hyperreactivity and as idiopathic rhinitis (IR) (synonyms frequently used in the past: non-specific nasal hyperreactivity; vasomotor rhinitis) in the case of non-characterised stimuli. An early and professional therapy of allergic disorders of the upper airways is of immense importance as allergic rhinitis is detected in comorbidities such as asthma and rhino sinusitis. The therapeutic concept is influenced by new and further developments in pharmacological substance classes such as antihistamines and glucocorticosteroids. Specific immune therapy, the only causal therapy for AR, has been reviewed over the past few years in respect of the type and pattern of application. However, to date no firm recommendations on oral, sublingual and /or nasal immune therapy have yet been drawn up based on investigations of these modifications. Therapeutic management of IR is aimed at a symptom-oriented therapy of nasal hyperactivity as etiological factors relating to this form of rhinitis are not yet sufficiently known. Drug groups such as mast cell stabilizers, systemic and topic antihistamines, topic and systemic glucocorticosteroids, ipatroium bromide and alpha symphatomimetics belong to the spectrum of the therapeutics employed. PMID:22073046

Visualization and Quantification of Nasal and Olfactory Deposition in a Sectional Adult Nasal Airway Cast.

PubMed

Xi, Jinxiang; Yuan, Jiayao Eddie; Zhang, Yu; Nevorski, Dannielle; Wang, Zhaoxuan; Zhou, Yue

2016-06-01

To compare drug deposition in the nose and olfactory region with different nasal devices and administration techniques. A Sar-Gel based colorimetry method will be developed to quantify local deposition rates. A sectional nasal airway cast was developed based on an MRI-based nasal airway model to visualize deposition patterns and measure regional dosages. Four nasal spray pumps and four nebulizers were tested with both standard and point-release administration techniques. Delivered dosages were measured using a high-precision scale. The colorimetry correlation for deposited mass was developed via image processing in Matlab and its performance was evaluated through comparison to experimental measurements. Results show that the majority of nasal spray droplets deposited in the anterior nose while only a small fraction (less than 4.6%) reached the olfactory region. For all nebulizers considered, more droplets went beyond the nasal valve, leading to distinct deposition patterns as a function of both the nebulizer type (droplet size and initial speed) and inhalation flow rate. With the point-release administration, up to 9.0% (±1.9%) of administered drugs were delivered to the olfactory region and 15.7 (±2.4%) to the upper nose using Pari Sinus. Standard nasal devices are inadequate to deliver clinically significant olfactory dosages without excess drug losses in other nasal epitheliums. The Sar-Gel based colorimetry method appears to provide a simple and practical approach to visualize and quantify regional deposition.

Flow through the nasal cavity of the spiny dogfish, Squalus acanthias

NASA Astrophysics Data System (ADS)

Timm-Davis, L. L.; Fish, F. E.

2015-12-01

The nasal cavity of spiny dogfish is a blind capsule with no internal connection to the oral cavity. Water is envisioned to flow through the cavity in a smooth, continuous flow pattern; however, this assumption is based on previous descriptions of the morphology of the olfactory cavity. No experimentation on the flow through the internal nasal cavity has been reported. Morphology of the head of the spiny dogfish ( Squalus acanthias) does not suggest a close external connection between the oral and nasal systems. However, dye visualization showed that there was flow through the nasal apparatus and from the excurrent nostril to the mouth when respiratory flows were simulated. The hydrodynamic flow through the nasal cavity was observed from flow tank experiments. The dorsum of the nasal cavity of shark heads from dead animals was exposed by dissection and a glass plate was glued over of the exposed cavity. When the head was placed in a flow, dye was observed to be drawn passively into the cavity showing a complex, three-dimensional hydrodynamic flow. Dye entered the incurrent nostril, flowed through the nasal lamellae, crossed over and under the nasal valve, and circulated around the nasal valve before exiting the excurrent nostril. When the nasal valve was removed, the dye became stagnant and back flowed out through the incurrent nostril. The single nasal valve has a hydrodynamic function that organizes a coherent flow of water through the cavity without disruption. The results suggest that the morphology of the nasal apparatus in concert with respiratory flow and ambient flows from active swimming can be used to draw water through the olfactory cavity of the shark.

Novel drug delivery systems for glaucoma

PubMed Central

Lavik, E; Kuehn, M H; Kwon, Y H

2011-01-01

Reduction of intraocular pressure (IOP) by pharmaceutical or surgical means has long been the standard treatment for glaucoma. A number of excellent drugs are available that are effective in reducing IOP. These drugs are typically applied as eye drops. However, patient adherence can be poor, thus reducing the clinical efficacy of the drugs. Several novel delivery systems designed to address the issue of adherence and to ensure consistent reduction of IOP are currently under development. These delivery systems include contact lenses-releasing glaucoma medications, injectables such as biodegradable micro- and nanoparticles, and surgically implanted systems. These new technologies are aimed at increasing clinical efficacy by offering multiple delivery options and are capable of managing IOP for several months. There is also a desire to have complementary neuroprotective approaches for those who continue to show progression, despite IOP reduction. Many potential neuroprotective agents are not suitable for traditional oral or drop formulations. Their potential is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. In this review, we discuss benefits and limitations of the current systems of delivery and application, as well as those on the horizon. PMID:21475311

Health risks associated with inhaled nasal toxicants.

PubMed

Feron, V J; Arts, J H; Kuper, C F; Slootweg, P J; Woutersen, R A

2001-05-01

Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and metabolism-based extrapolation of nasal data in animals to humans. Conspicuous findings in humans are the effects of outdoor air pollution on the nasal mucosa, and tobacco smoking as a risk factor for sinonasal squamous cell carcinoma. Objective methods in humans to discriminate between sensory irritation and olfactory stimulation and between adaptation and habituation have been introduced successfully, providing more relevant information than sensory irritation studies in animals. Against the background of chemoperception as a dominant window of the brain on the outside world, nasal neurotoxicology is rapidly developing, focusing on olfactory and trigeminal nerve toxicity. Better insight in the processes underlying neurogenic inflammation may increase our knowledge of the causes of the various chemical sensitivity syndromes. Nasal immunotoxicology is extremely complex, which is mainly due to the pivotal role of nasal lymphoid tissue in the defense of the middle ear, eye, and oral cavity against antigenic substances, and the important function of the nasal passages in brain drainage in rats. The crucial role of tissue damage and reactive epithelial hyperproliferation in nasal carcinogenesis has become overwhelmingly clear as demonstrated by the recently developed biologically based model for predicting formaldehyde nasal cancer risk in humans. The evidence of carcinogenicity of inhaled complex mixtures in experimental animals is very limited, while there is ample evidence that occupational exposure to mixtures such as wood, leather, or textile dust or chromium- and nickel-containing materials is associated with increased risk of nasal cancer. It is remarkable that these

Nasal packing and stenting

PubMed Central

Weber, Rainer K.

2011-01-01

Nasal packs are indispensable in ENT practice. This study reviews current indications, effectiveness and risks of nasal packs and stents. In endoscopic surgery, nasal packs should always have smooth surfaces to minimize mucosal damage, improve wound healing and increase patient comfort. Functional endoscopic endonasal sinus surgery allows the use of modern nasal packs, since pressure is no longer required. So called hemostatic/resorbable materials are a first step in this direction. However, they may lead to adhesions and foreign body reactions in mucosal membranes. Simple occlusion is an effective method for creating a moist milieu for improved wound healing and avoiding dryness. Stenting of the frontal sinus is recommended if surgery fails to produce a wide, physiologically shaped drainage path that is sufficiently covered by intact tissue. PMID:22073095

Appraisal of transverse nasal groove: a study.

PubMed

Sathyanarayana, Belagola D; Basavaraj, Halevoor B; Nischal, Kuchangi C; Swaroop, Mukunda R; Umashankar, Puttagangu N; Agrawal, Dhruv P; Swamy, Suchetha S; Okram, Sarda

2012-01-01

Transverse nasal groove is a condition of cosmetic concern which awaits due recognition and has been widely described as a shallow groove that extends transversely over the dorsum of nose. However, we observed variations in the clinical presentations of this entity, hitherto undescribed in literature. We conducted a clinicoepidemiological study of transverse nasal lesions in patients attending our outpatient department. We conducted a prospective observational study. We screened all patients attending our out-patient department for presence of transverse nasal lesions, signs of any dermatosis and associated other skin conditions. One hundred patients were recruited in the study. Females (80%) predominated over males. Most patients were of 15-45 years age group (70%). Majority of the transverse nasal lesions were classical transverse nasal groove (39%) and others included transverse nasal line (28%), strip (28%), ridge (4%) and loop (1%). Seborrhoeic diathesis was the most common condition associated with transverse nasal lesion. Occurrence of transverse nasal line, strip, ridge and loop, in addition to classical transverse nasal groove implies that latter is actually a subset of transverse nasal lesions. Common association of this entity with seborrheic dermatitis, seborrhea and dandruff raises a possibility of whether transverse nasal lesion is a manifestation of seborrheic diathesis.

CpG Oligodeoxynucleotides Facilitate Delivery of Whole Inactivated H9N2 Influenza Virus via Transepithelial Dendrites of Dendritic Cells in Nasal Mucosa

PubMed Central

Qin, Tao; Yin, Yinyan; Yu, Qinghua; Huang, Lulu; Wang, Xiaoqing; Lin, Jian

2015-01-01

ABSTRACT The spread of the low-pathogenicity avian H9N2 influenza virus has seriously increased the risk of a new influenza pandemic. Although whole inactivated virus (WIV) vaccine via intranasal pathway is the effective method of blocking virus transmission, the mucosal barrier seems to be a major factor hampering its development. CpG oligodeoxynucleotides, a known adjuvant, can target downstream dendritic cells (DCs) and effectively enhance the mucosal and systemic immune responses. However, the ability of CpGs to assist H9N2 WIV in transepithelial transport remains unknown. Here, in vitro and in vivo, we showed that CpGs provided assistance for H9N2 WIV in recruiting DCs to the nasal epithelial cells (ECs) and forming transepithelial dendrites (TEDs) to capture luminal viruses. CD103+ DCs participated in this process. Chemokine CCL20 from nasal ECs played a key role in driving DC recruitment and TED formation. Virus-loaded DCs quickly migrated into the draining cervical lymph nodes (CLNs) for antigen presentation. In addition, the competence of CpGs was independent of direct epithelial transport via the transcellular or paracellular pathway. Taken together, our data demonstrated that CpGs enhanced the transport of H9N2 WIV via TEDs of nasal DCs, which might be a novel mechanism for optimal adaptive immune responses. IMPORTANCE This paper demonstrates by both an in vivo and an in vitro coculture model that CpG oligodeoxynucleotides, known as an adjuvant generally targeting downstream immune responses, also are crucial for the transport of H9N2 WIV across nasal epithelial cells (ECs) via the uptake of transepithelial dendrites (TEDs). Our results prove for the first time to our knowledge that the immune-potentiating mechanism of CpGs is based on strengthening the transepithelial uptake of H9N2 WIV in nasal mucosa. These findings provide a fresh perspective for further improvement of intranasal influenza vaccines, which are urgently needed in the face of the

Drug delivery systems with modified release for systemic and biophase bioavailability.

PubMed

Leucuta, Sorin E

2012-11-01

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

Systems approaches evaluating the perturbation of xenobiotic metabolism in response to cigarette smoke exposure in nasal and bronchial tissues.

PubMed

Iskandar, Anita R; Martin, Florian; Talikka, Marja; Schlage, Walter K; Kostadinova, Radina; Mathis, Carole; Hoeng, Julia; Peitsch, Manuel C

2013-01-01

Capturing the effects of exposure in a specific target organ is a major challenge in risk assessment. Exposure to cigarette smoke (CS) implicates the field of tissue injury in the lung as well as nasal and airway epithelia. Xenobiotic metabolism in particular becomes an attractive tool for chemical risk assessment because of its responsiveness against toxic compounds, including those present in CS. This study describes an efficient integration from transcriptomic data to quantitative measures, which reflect the responses against xenobiotics that are captured in a biological network model. We show here that our novel systems approach can quantify the perturbation in the network model of xenobiotic metabolism. We further show that this approach efficiently compares the perturbation upon CS exposure in bronchial and nasal epithelial cells in vivo samples obtained from smokers. Our observation suggests the xenobiotic responses in the bronchial and nasal epithelial cells of smokers were similar to those observed in their respective organotypic models exposed to CS. Furthermore, the results suggest that nasal tissue is a reliable surrogate to measure xenobiotic responses in bronchial tissue.

Systems Approaches Evaluating the Perturbation of Xenobiotic Metabolism in Response to Cigarette Smoke Exposure in Nasal and Bronchial Tissues

PubMed Central

Iskandar, Anita R.; Martin, Florian; Talikka, Marja; Schlage, Walter K.; Mathis, Carole; Hoeng, Julia; Peitsch, Manuel C.

2013-01-01

Capturing the effects of exposure in a specific target organ is a major challenge in risk assessment. Exposure to cigarette smoke (CS) implicates the field of tissue injury in the lung as well as nasal and airway epithelia. Xenobiotic metabolism in particular becomes an attractive tool for chemical risk assessment because of its responsiveness against toxic compounds, including those present in CS. This study describes an efficient integration from transcriptomic data to quantitative measures, which reflect the responses against xenobiotics that are captured in a biological network model. We show here that our novel systems approach can quantify the perturbation in the network model of xenobiotic metabolism. We further show that this approach efficiently compares the perturbation upon CS exposure in bronchial and nasal epithelial cells in vivo samples obtained from smokers. Our observation suggests the xenobiotic responses in the bronchial and nasal epithelial cells of smokers were similar to those observed in their respective organotypic models exposed to CS. Furthermore, the results suggest that nasal tissue is a reliable surrogate to measure xenobiotic responses in bronchial tissue. PMID:24224167

Nasal budesonide offers superior symptom relief in perennial allergic rhinitis in comparison to nasal azelastine.

PubMed

Stern, M A; Wade, A G; Ridout, S M; Cambell, L M

1998-10-01

Allergic rhinitis is usually treated with oral antihistamines or nasal steroids. Topically active nasal antihistamine is a new treatment modality for allergic rhinitis. The efficacy in comparison to well established topical treatment alternatives is not fully known. To compare the efficacy of intranasally administered azelastine to budesonide, at their respectively recommended dosage, on the symptoms of perennial rhinitis patients. A placebo-controlled, randomized, parallel group study was conducted to compare the efficacy and tolerability of intranasal budesonide aqueous suspension (256 microg once daily) with azelastine hydrochloride nasal spray (280 microg twice daily (560 microg/day)) and with placebo in the treatment of perennial allergic rhinitis. The 195 patients (with at least a 2-year history of perennial allergic rhinitis) recorded individual nasal symptom scores, the degree of symptom control achieved and any adverse events experienced over a 2-week baseline period and a 6-week treatment period. Following treatment, the reductions in mean combined and individual nasal symptom scores from baseline values were significantly greater in the budesonide group compared with the placebo group (P < .0001 for all variables except runny nose P = .01). In patients treated with budesonide, there were also significantly larger reductions from baseline values in combined nasal symptom scores (P < .01) and in scores for all individual nasal symptoms (P < or = .05) compared with those treated with azelastine. The reductions from baseline in both combined and individual nasal symptom scores did not differ between azelastine and placebo. The study medications were well tolerated, producing no unexpected or serious treatment-related adverse events. A once-daily dose of 256 microg of intranasal budesonide aqueous suspension is significantly more effective at relieving the symptoms of perennial allergic rhinitis compared with a twice daily dose of 280 microg of azelastine

Continuous Positive Airway Pressure Strategies with Bubble Nasal Continuous Positive Airway Pressure: Not All Bubbling Is the Same: The Seattle Positive Airway Pressure System.

PubMed

Welty, Stephen E

2016-12-01

Premature neonates are predisposed to complications, including bronchopulmonary dysplasia (BPD). BPD is associated with long-term pulmonary and neurodevelopmental consequences. Noninvasive respiratory support with nasal continuous positive airway pressure (CPAP) has been recommended strongly by the American Academy of Pediatrics. However, CPAP implementation has shown at least a 50% failure rate. Enhancing nasal CPAP effectiveness may decrease the need for mechanical ventilation and reduce the incidence of BPD. Bubble nasal CPAP is better than nasal CPAP using mechanical devices and the bubbling provides air exchange in distal respiratory units. The Seattle PAP system reduces parameters that assess work of breathing. Copyright © 2016 Elsevier Inc. All rights reserved.

Safety assessment of thiolated polymers: effect on ciliary beat frequency in human nasal epithelial cells.

PubMed

Palmberger, Thomas F; Augustijns, Patrick; Vetter, Anja; Bernkop-Schnürch, Andreas

2011-12-01

The aim of this study was to investigate the nasal safety of gel formulations of thiolated polymers (thiomers) by assessing their effect on ciliary beat frequency (CBF) in human nasal epithelial cells. Poly(acrylic acid) 450 kDa-cysteine (PAA-cys) and alginate-cysteine (alg-cys) were synthesized by covalent attachment of L-cysteine to the polymeric backbone. The cationic polymer chitosan-thiobutylamidine (chito-TBA) was synthesized by attaching iminothiolane to chitosan. CBF using was measured by a photometric system. CBF was measured before incubating the cells with test gels, during incubation and after washing out the polymeric test gels to evaluate reversibility of cilio-inhibition. The influence of viscosity on CBF was determined by using hydroxyethylcellulose (HEC)-gels of various concentrations. Ciliary beating was observed to be affected by viscosity, but cilia were still beating in the presence of a HEC-gel displaying an apparent viscosity of 25 Pa.s. In case of thiolated polymers and their unmodified control, a concentration-dependent decrease in CBF could be observed. PAA-cys, alg-cys, chito-TBA and their corresponding unmodified controls exhibited a moderate cilio-inhibitory effect, followed by a partial recovery of CBF when used at a concentration of 1%. Alg-cys 2% and chito-TBA 2% (m/v) gels exhibited severe cilio-inhibition, which was partially reversible. L-cysteine and reduced glutathione led to mild cilio-inhibition at concentrations of 3% (m/v). Taking into account that dilution after application and cilio-modifying effects is usually more pronounced under in vitro conditions, thiomers can be considered as suitable excipients for nasal drug delivery systems.

Nasal symptoms following endoscopic transsphenoidal pituitary surgery: assessment using the General Nasal Patient Inventory.

PubMed

Wang, Yi Yuen; Srirathan, Vinothan; Tirr, Erica; Kearney, Tara; Gnanalingham, Kanna K

2011-04-01

The endoscopic approach for pituitary tumors is a recent innovation and is said to reduce the nasal trauma associated with transnasal transsphenoidal surgery. The authors assessed the temporal changes in the rhinological symptoms following endoscopic transsphenoidal surgery for pituitary lesions, using the General Nasal Patient Inventory (GNPI). The GNPI was administered to 88 consecutive patients undergoing endoscopic transsphenoidal surgery at 3 time points (presurgery, 3-6 months postsurgery, and at final follow-up). The total GNPI score and the scores for the individual GNPI questions were calculated and differences between groups were assessed once before surgery, several months after surgery, and at final follow-up. Of a maximum possible score of 135, the mean GNPI score at 3-6 months postsurgery was only 12.9 ± 12 and was not significantly different from the preoperative score (10.4 ± 13) or final follow-up score (10.3 ± 10). Patients with functioning tumors had higher GNPI scores than those with nonfunctioning tumors for each of these time points (p < 0.05). Individually, a mild increase in symptom severity was seen for symptoms attributable to the nasal trauma of surgery, with partial recovery (nasal sores and bleeding) or complete recovery (nasal blockage, painful sinuses, and unpleasant nasal smell) by final follow-up (p < 0.05). Progressive improvements in symptom severity were seen for symptoms more attributable to tumor mass preoperatively (for example, headaches and painkiller use [p < 0.05]). In total, by final follow-up 8 patients (9%) required further treatment or advice for ongoing nasal symptoms. Endoscopic transsphenoidal surgery is a well-tolerated minimally invasive procedure for pituitary fossa lesions. Overall patient-assessed nasal symptoms do not change, but some individual symptoms may show a mild worsening or overall improvement.

Elastic liposomes as novel carriers: recent advances in drug delivery

PubMed Central

Hussain, Afzal; Singh, Sima; Sharma, Dinesh; Webster, Thomas J; Shafaat, Kausar; Faruk, Abdul

2017-01-01

Elastic liposomes (EL) are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. PMID:28761343

Elastic liposomes as novel carriers: recent advances in drug delivery.

PubMed

Hussain, Afzal; Singh, Sima; Sharma, Dinesh; Webster, Thomas J; Shafaat, Kausar; Faruk, Abdul

2017-01-01

Elastic liposomes (EL) are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields.

Adjuncts to Improve Nasal Reconstruction Results.

PubMed

Gordon, Shayna Lee; Hurst, Eva A

2017-02-01

The final cosmetic appearance of nasal reconstruction scars is of paramount importance to both the patient and surgeon. Ideal postreconstruction nasal scars are flat and indistinguishable from surrounding skin. Unfortunately, even with meticulous surgical execution, nasal scars can occasionally be suboptimal. Abnormal fibroblast response can lead to hypertrophic nasal scars, and excessive angiogenesis may lead to telangiectasias or an erythematous scar. Imperfect surgical closure or poor postoperative management can lead to surgical outcomes with step-offs, depressions, suture marks, or dyspigmentation. Aesthetically unacceptable nasal scars can cause pruritus, tenderness, pain, sleep disturbance, and anxiety and depression in postsurgical patients. Fortunately, there are several minimally invasive or noninvasive techniques that allow for enhancement and improvement of cosmetic results with minimal risk and associated downtime. This article provides an overview of adjuncts to improve nasal reconstruction with a focus on techniques to be used in the postoperative period. Armed with an understanding of relevant available therapies, skillful surgeons may drastically improve the final cosmesis and outcome of nasal reconstruction scars. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Radiation delivery system and method

DOEpatents

Sorensen, Scott A.; Robison, Thomas W.; Taylor, Craig M. V.

2002-01-01

A radiation delivery system and method are described. The system includes a treatment configuration such as a stent, balloon catheter, wire, ribbon, or the like, a portion of which is covered with a gold layer. Chemisorbed to the gold layer is a radiation-emitting self-assembled monolayer or a radiation-emitting polymer. The radiation delivery system is compatible with medical catheter-based technologies to provide a therapeutic dose of radiation to a lesion following an angioplasty procedure.

Delivery of therapeutics for deep-seated ocular conditions - status quo.

PubMed

Nguyen, Hubert; Eng, Shawn; Ngo, Thanh; Dass, Crispin R

2018-04-19

There is a need for research into designing effective pharmaceutical systems for delivering therapeutic drugs to the posterior of the eye for glaucoma-related pathology, macular degeneration, diabetic retinopathy, macular oedema, retinitis and choroiditis. Conventionally, eye drops have been extensively utilised for topical drug delivery to the anterior segment of the eye, but are less effective for delivery of therapeutics to the back of the eye due to significant barriers hampering drug penetration into the target intraocular tissue. This review explores some of the current and novel delivery systems employed to deliver therapeutics to the back of the eye such as those using liposomes, ocular implants, in situ gels, and nanoparticles, and how they can overcome some of these limitations. Issues such as blinking, precorneal fluid drainage, tear dilution and turnover, conjunctiva and nasal drug absorption, the corneal epithelium, vitreous drug clearance, and the blood-ocular barriers are reviewed and discussed. Further studies are needed to address their shortcomings such as drug compatibility and stability, economic viability and patient compliance. © 2018 Royal Pharmaceutical Society.

Presurgical Nasal Molding With a Nasal Spring in Patients With Mild-to-Moderate Nasal Deformity With Incomplete Unilateral Cleft Lip With or Without Cleft Palate.

PubMed

Peanchitlertkajorn, Supakit

2018-01-01

Traditional nasoalveolar molding (NAM) requires steep learning curve for clinicians and significant compliance from parents. Nasal springs have been developed by the author to simplify presurgical nasal molding. This article presents the design, construction, and application of the spring. The treatment goal is to improve nasal deformity prior to primary repair in infants born with incomplete unilateral cleft lip with or without cleft palate. The design, fabrication, and utility of the nasal spring are described. The spring has a simpler design and construction compared to a traditional NAM appliance. Two patients with incomplete unilateral cleft lip with and without cleft palate are presented. The spring is constructed and delivered. The active arm of the spring can be 3-dimensionally (3-D) adjusted to mold the alar cartilage of the affected nostril. The spring does not require an oral plate for adherence as a traditional NAM appliance does, hence an oral impression is not needed. The spring is easy for clinicians to adjust. It also requires less compliance by parents. Main Outcome Measures/Results: The presurgical molding achieved by the use of a nasal spring improved surgical nasolabial aesthetic outcomes. The nasal springs are effective in reducing the initial cleft nasal deformity. This facilitates primary surgical cleft lip and nose correction and improves surgical outcomes in patients with incomplete unilateral cleft lip with or without cleft palate.

Management of Intractable Nasal Hyperreactivity by Selective Resection of Posterior Nasal Nerve Branches

PubMed Central

Takahara, Daisuke; Hamamoto, Takao; Ishino, Takashi; Hirakawa, Katsuhiro

2017-01-01

The posterior nasal nerves emerge from the sphenopalatine foramen and contain sensory and autonomic nerve components. Posterior nasal neurectomy is an effective method to remove pathological neural networks surrounding the inferior turbinate that cause unregulated nasal hypersensitivity with excess secretion in patients with severe allergic rhinitis (AR). We describe the sophisticated endoscopic surgical procedure that allows feasible access to the confined area and selective resection of the nerve branches with the preservation of the sphenopalatine artery (SPA). We retrospectively analyzed the cases of 23 symptomatic severe AR patients who failed to respond to standard medical treatment and underwent surgery. There have been no major complications after surgery including nasal bleeding or transient numbness of the upper teeth. The mean total nasal symptom scores (TNSS) were decreased by 70.2% at 12 months after the procedure. Our comparison of the clinical effectiveness based on the number of severed nerve branches revealed that the improvement of the TNSS was significantly higher in patients with >2 branches. We conclude that this minimally invasive technique that preserves the SPA is clinically useful and decreases the rate of postoperative complications. This trial is registered with UMIN000029025. PMID:29379524

Management of Intractable Nasal Hyperreactivity by Selective Resection of Posterior Nasal Nerve Branches.

PubMed

Takahara, Daisuke; Takeno, Sachio; Hamamoto, Takao; Ishino, Takashi; Hirakawa, Katsuhiro

2017-01-01

The posterior nasal nerves emerge from the sphenopalatine foramen and contain sensory and autonomic nerve components. Posterior nasal neurectomy is an effective method to remove pathological neural networks surrounding the inferior turbinate that cause unregulated nasal hypersensitivity with excess secretion in patients with severe allergic rhinitis (AR). We describe the sophisticated endoscopic surgical procedure that allows feasible access to the confined area and selective resection of the nerve branches with the preservation of the sphenopalatine artery (SPA). We retrospectively analyzed the cases of 23 symptomatic severe AR patients who failed to respond to standard medical treatment and underwent surgery. There have been no major complications after surgery including nasal bleeding or transient numbness of the upper teeth. The mean total nasal symptom scores (TNSS) were decreased by 70.2% at 12 months after the procedure. Our comparison of the clinical effectiveness based on the number of severed nerve branches revealed that the improvement of the TNSS was significantly higher in patients with >2 branches. We conclude that this minimally invasive technique that preserves the SPA is clinically useful and decreases the rate of postoperative complications. This trial is registered with UMIN000029025.

Communications data delivery system analysis task 2 report : high-level options for secure communications data delivery systems.

DOT National Transportation Integrated Search

2012-05-16

This Communications Data Delivery System Analysis Task 2 report describes and analyzes options for Vehicle to Vehicle (V2V) and Vehicle to Infrastructure (V2I) communications data delivery systems using various communication media (Dedicated Short Ra...

Intranasal Delivery of Topically-Acting Levofloxacin to Rats: a Proof-of-Concept Pharmacokinetic Study.

PubMed

Sousa, Joana; Alves, Gilberto; Fortuna, Ana; Falcão, Amílcar

2017-11-01

To evaluate the potential of levofloxacin intranasal administration as a promising alternative approach to treat local infections such as chronic rhinosinusitis, by delivering drug concentrations directly to the site of infection. Drug concentrations were measured in plasma, olfactory bulb and nasal mucosa of anterior (ANM) and posterior regions after intranasal (0.24 mg/kg) and intravenous (10 mg/kg) administration to rats, and pharmacokinetic parameters were compared between routes. For intranasal administration a thermoreversible in-situ gel was used. Plasma and olfactory bulb exposure to levofloxacin was minimal following intranasal dose, preventing systemic and central nervous system adverse effects. Levofloxacin concentration-time profile in ANM revealed higher concentrations during the first 60 min of the study following intranasal administration than the corresponding ones obtained after intravenous administration. A rapid and continuous decay of levofloxacin concentration in this nasal region was observed after intranasal delivery, resulting in much lower values at the last sampling time-points. The higher dose-normalized concentrations and pharmacokinetic exposure parameters of levofloxacin in ANM after intranasal administration, demonstrates that intranasal delivery of the formulated gel is, by itself, advantageous for delivering levofloxacin to biophase and thus an attractive approach in management of chronic rhinosinusitis.

[Disturbances of nasal aerodynamics in patients with the curved nasal septum and the rationale for its surgical correction].

PubMed

Tulebaev, R K; Mustafin, A A; Zholdybaeva, Z T

2011-01-01

Serious disturbances of nasal aerodynamics contribute to the development of diseases of the broncho-pulmonary apparatus. The early recognition of ventilation problems in patients with the curved nasal septum is paramount for the efficacious prevention and treatment of respiratory complications. The authors describe principles of rhinosurgical correction of affected nasal aerodynamics in patients with the curved nasal septum.

Nasal polyposis (or chronic olfactory rhinitis).

PubMed

Jankowski, R; Rumeau, C; Gallet, P; Nguyen, D T

2018-06-01

The concept of chronic rhinosinusitis with or without polyps is founded on the structural and functional unicity of the pituitary mucosa and its united response to environmental aggression by allergens, viruses, bacteria, pollution, etc. The present review sets this concept against the evo-devo three-nose theory, in which nasal polyposis is distinguished as specific to the olfactory nose and in particular to the non-olfactory mucosa of the ethmoid, which is considered to be not a sinus but rather the skull-base bone harboring the olfactory mucosa. The evo-devo approach enables simple and precise positive diagnosis of nasal polyposis and its various clinical forms, improves differential diagnosis by distinguishing chronic diseases of the respiratory nose and those of the paranasal sinuses, hypothesizes an autoimmune origin specifically aimed at olfactory system auto-antigens, and supports the surgical concept of nasalization against that of functional sinus and ostiomeatal-complex surgery. The ventilation function of the sinuses seems minor compared to their production, storage and active release of nitric oxide (NO) serving to oxygenate arterial blood in the pulmonary alveoli. This respiratory function of the paranasal sinuses may indeed be their most important. NO trapped in the ethmoidal spaces also accounts for certain radiographic aspects associated with nasal polyposis. Copyright © 2018. Published by Elsevier Masson SAS.

New surgical concepts: nasal tip function.

PubMed

Galli, J J; Zavalla, C A; Vivas, D G; Prado, C; Zanetta, G C

1997-01-01

Since the birth of plastic surgery, rhinoplasty has been an outstanding chapter. Facial balance has been endeavoured with two parameters: size and shape. Now, however, the criterion for harmony has involved two more parameters; position and function. Position is related to other facial elements, such as, upper maxilla, upper lip, forehead, and frontonasal sulcus. Function is important because nasal superficial musculoaponeurotic system (SMAS) muscles are important for Nasal tip movement. To understand this better, we must analyze the nasal SMAS, which consists of primary or intrinsic and secondary or extrinsic muscles. When the extrinsics contract, they allow function of the intrinsics. They are the ala nasalis dilator, the ala nasalis elevator, the tranversus, and the tip depressor. Obvious hypertrophies of the dilator and the elevator has been observed in young athletes. Our method combines conventional, new, and modern aspects. It is conventional because the alar cartilages have been completely freed by intercartilaginous and marginal approaches, and the upper or lower border trimmed according to the case. It is more important to measure how much cartilage is left, than how much is removed. The new aspect is consideration of nasal SMAS to treat short noses that display a tendency to descend with laughter, and the modern aspect is the evaluation of dynamic surgical results, apart from the static.

Analytical Challenges and Regulatory Requirements for Nasal Drug Products in Europe and the U.S.

PubMed Central

Trows, Sabrina; Wuchner, Klaus; Spycher, Rene; Steckel, Hartwig

2014-01-01

Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results. PMID:24732068

Stabilization and delivery approaches for protein and peptide pharmaceuticals: an extensive review of patents.

PubMed

Swain, Suryakanta; Mondal, Debanik; Beg, Sarwar; Patra, Chinam Niranjan; Dinda, Subas Chandra; Sruti, Jammula; Rao, Muddana Eswara Bhanoji

2013-04-01

Proteins and peptides are the building blocks of human body and act as the arsenal to combat against the invading pathogenic organisms for treatment and management of diseases. Majority of such biomacromolecules are synthesized by the human body itself. However, entry of disease causing pathogens causes misleading in the synthesis of desired proteins for antibody formation. In such alarming situations, the delivery of requisite protein and peptide from external source helps in augmenting the body's immunity. The major drawbacks underlying poor biopharmaceutical performance of high molecular weight protein and peptide drugs are due to poor oral absorption, formulation stability, degradation in the gastric milieu, susceptible to presystemic metabolism. Numerous literature recounts the application of myriad drug delivery strategies for the effective delivery of protein and peptides viz. parentral, oral, transdermal, nasal, pulmonary, rectal, buccal and ocular drug delivery systems. There are many reviews on various delivery strategies for protein and peptide pharmaceuticals, but the present review article provides a bird's eye view on various novel drug delivery systems used for enhanced delivery of protein and peptide pharmaceuticals in the light of patent literature. Apart from this, the present manuscript endeavor provides idea on possible causes and major degradation pathways responsible for poor stability of protein and peptide drugs along with recent market instances on them utilizing novel drug delivery systems.

Levodopa delivery systems: advancements in delivery of the gold standard.

PubMed

Ngwuluka, Ndidi; Pillay, Viness; Du Toit, Lisa C; Ndesendo, Valence; Choonara, Yahya; Modi, Girish; Naidoo, Dinesh

2010-02-01

Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors. Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated. The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated. This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the

Oxymetazoline plus dexpanthenol in nasal congestion.

PubMed

Jagade, Mohan V; Langade, Deepak G; Pophale, Rupesh R; Prabhu, Arun

2008-12-01

To compare the efficacy and tolerability of Oxymetazoline 0.05 % plus Dexpanthanol 5% versus Xylometazoline 0.1 % nasal drops in patients with nasal congestion due to allergic rhinitis and following nasal surgery. An investigator-blind, randomized, controlled, phase IV clinical trial conducted in 100 patients with acute allergic rhinitis or patients post-nasal surgery. Patients received either Oxymetazoline 0.05% with Dexpanthanol 5% (OD) or Xylometazoline 0.1% (XO) nasal drops. Relief from nasal congestion was significantly better in the OD group then in the XO group (mean nasal scores 1.24 vs 1.86). Significantly more improvement in sneezing and decrease in nasal discharge was seen in the OD group than the XO group. Nasal irritation in the OD group was significantly less as compared to XO group (0.38 v/s 1.12 on second day and 0.10 vs 0.36 on the fourth day). The recovery time for OD group was 1.08 hours, which was significantly (46 min) lesser than that of the XO group. Rebound congestion was significantly less in OD as compared to XO group (6.25% vs 82.98%). 93.75% of the physicians in the OD group and 51.28% in XO group reported response to therapy as good to excellent. 95.83% patients in the OD group and only 52.91% patients in the XO group rated tolerability to therapy as good to excellent. Oxymetazoline and dexpanthenol combination has a better efficacy, shorter recovery time, causes lesser rebound congestion and has better tolerability than xylometazoline.

Recent developments in leishmaniasis vaccine delivery systems.

PubMed

Bhowmick, Sudipta; Ali, Nahid

2008-07-01

The observation that recovery from infection with Leishmania confers immunity to reinfection suggests that control of leishmaniasis by vaccination may be possible. New generation vaccines, particularly those based on recombinant proteins and DNA, are found to be less immunogenic. There is an urgent need for the development of new and improved vaccine adjuvants. Based on their principal mechanisms of action, adjuvants can be broadly separated into two classes: immunostimulatory adjuvants and vaccine delivery systems. Vaccine delivery systems can carry both antigen and adjuvant for effective delivery to the antigen-presenting cells (APCs). In this article, we review the adjuvants, the delivery systems and their combinations used in the search of an effective vaccine against leishmaniasis. Based on current knowledge, cationic liposomes appear to have better prospects as effective delivery systems for developing a vaccine for leishmaniasis.

Drug delivery.

PubMed

Le Souëf, Peter N

2002-09-16

What we know: In preschool children, small-volume spacers perform better than large-volume spacers. Detergent is the best antistatic agent for spacers, increasing lung delivery two- to threefold, but it must not be rinsed off. A mouthpiece should be used in children aged 2-3 years or older, as lung delivery is two- to threefold higher for oral inhalation than nasal inhalation (ie, by mask). Inhaled drug doses do not generally need to be reduced in infants and young children owing to inefficiencies of delivery in younger patients. Nebulisers are "dinosaurs" and not needed for most children with asthma. What we need to know: What is the best inhalation technique for spacers? How long should children breathe, how many breaths should they take, and at what age should they breath-hold? How should children, parents and doctors be instructed to achieve optimal levels of electrostatic charge reduction for spacers? How much should inhaled steroid dose be reduced when a spacer is used optimally? What dosing instructions should be given for beta(2)-agonists delivered by spacer?

Development of thiolated poly(acrylic acid) microparticles for the nasal administration of exenatide.

PubMed

Millotti, Gioconda; Vetter, Anja; Leithner, Katharina; Sarti, Federica; Shahnaz Bano, Gul; Augustijns, Patrick; Bernkop-Schnürch, Andreas

2014-12-01

The purpose of this study was to develop a microparticulate formulation for nasal delivery of exenatide utilizing a thiolated polymer. Poly(acrylic acid)-cysteine (PAA-cys) and unmodified PAA microparticles loaded with exenatide were prepared via coprecipitation of the drug and the polymer followed by micronization. Particle size, drug load and release of incorporated exenatide were evaluated. Permeation enhancing properties of the formulations were investigated on excised porcine respiratory mucosa. The viability of the mucosa was investigated by histological studies. Furthermore, ciliary beat frequency (CBF) studies were performed. Microparticles displayed a mean size of 70-80 µm. Drug encapsulation was ∼80% for both thiolated and non-thiolated microparticles. Exenatide was released from both thiolated and non-thiolated particles in comparison to exenatide in buffer only within 40 min. As compared to exenatide dissolved in buffer only, non-thiolated and thiolated microparticles resulted in a 2.6- and 4.7-fold uptake, respectively. Histological studies performed before and after permeation studies showed that the mucosa is not damaged during permeation studies. CBF studies showed that the formulations were cilio-friendly. Based on these results, poly(acrylic acid)-cysteine-based microparticles seem to be a promising approach starting point for the nasal delivery of exenatide.

A new Strategy to Improve Drug Delivery to the Maxillary Sinuses: The Frequency Sweep Acoustic Airflow.

PubMed

El Merhie, Amira; Navarro, Laurent; Delavenne, Xavier; Leclerc, Lara; Pourchez, Jérémie

2016-05-01

Enhancement of intranasal sinus deposition involves nebulization of a drug superimposed by an acoustic airflow. We investigated the impact of fixed frequency versus frequency sweep acoustic airflow on the improvement of aerosolized drug penetration into maxillary sinuses. Fixed frequency and frequency sweep acoustic airflow were generated using a nebulizing system of variable frequency. The effect of sweep cycle and intensity variation was studied on the intranasal sinus deposition. We used a nasal replica created from CT scans using 3D printing. Sodium fluoride and gentamicin were chosen as markers. Studies performed using fixed frequency acoustic airflow showed that each of maxillary sinuses of the nasal replica required specific frequency for the optimal aerosol deposition. Intranasal sinus drug deposition experiments under the effect of the frequency sweep acoustic airflow showed an optimal aerosol deposition into both maxillary sinus of the nasal replica. Studies on the effect of the duration of the sweep cycle showed that the shorter the cycle the better the deposition. We demonstrate the benefit of frequency sweep acoustic airflow on drug deposition into maxillary sinuses. However further in vivo studies have to be conducted since delivery rates cannot be obviously determined from a nasal replica.

Nasal dermoid sinus cyst.

PubMed

Cauchois, R; Laccourreye, O; Bremond, D; Testud, R; Küffer, R; Monteil, J P

1994-08-01

Nasal dermoid sinus cyst is one of the diagnoses of midline nasal masses in children. This retrospective study analyzes the various theories regarding the origin of this congenital abnormality, the differential diagnosis, and the value of magnetic resonance imaging, as well as the various surgical options available.

Topical drug delivery systems: a patent review.

PubMed

Singh Malik, Deepinder; Mital, Neeraj; Kaur, Gurpreet

2016-01-01

Topical administration is the favored route for local delivery of therapeutic agents due to its convenience and affordability. The specific challenge of designing a therapeutic system is to achieve an optimal concentration of a certain drug at its site of action for an appropriate duration. This review summarizes innovations from the past 3 years (2012-2015) in the field of topical drug delivery for the treatment of local infections of the vagina, nose, eye and skin. The review also throws some light on the anatomy and physiology of these organs and their various defensive barriers which affect the delivery of drugs administered topically. Topical administration has been gaining attention over the last few years. However, conventional topical drug delivery systems suffer from drawbacks such as poor retention and low bioavailability. The successful formulation of topical delivery products requires the careful manipulation of defensive barriers and selection of a soluble drug carrier. Extensive research is required to develop newer topical drug delivery systems aiming either to improve the efficacy or to reduce side effects compared to current patented systems.

Anthrax vaccine powder formulations for nasal mucosal delivery.

PubMed

Jiang, Ge; Joshi, Sangeeta B; Peek, Laura J; Brandau, Duane T; Huang, Juan; Ferriter, Matthew S; Woodley, Wendy D; Ford, Brandi M; Mar, Kevin D; Mikszta, John A; Hwang, C Robin; Ulrich, Robert; Harvey, Noel G; Middaugh, C Russell; Sullivan, Vincent J

2006-01-01

Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and formulation development of such powder formulations. The physical stability of rPA was studied in solution as a function of pH and temperature using circular dichroism (CD), and UV-visible absorption and fluorescence spectroscopies. Extensive aggregation of rPA was observed at physiological temperatures. An empirical phase diagram, constructed using a combination of CD and fluorescence data, suggests that rPA is most thermally stable within the pH range of 6-8. To identify potential stabilizers, a library of GRAS excipients was screened using an aggregation sensitive turbidity assay, CD, and fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7-8 using trehalose as stabilizer and a CpG-containing oligonucleotide adjuvant. SFD formulations displayed substantial improvement in storage stability over liquid formulations. In combination with noninvasive intranasal delivery, such powder formulations may offer an attractive approach for mass biodefense immunization.

Speech rate reduction and "nasality" in normal speakers.

PubMed

Brancewicz, T M; Reich, A R

1989-12-01

This study explored the effects of reduced speech rate on nasal/voice accelerometric measures and nasality ratings. Nasal/voice accelerometric measures were obtained from normal adults for various speech stimuli and speaking rates. Stimuli included three sentences (one obstruent-loaded, one semivowel-loaded, and one containing a single nasal), and /pv/ syllable trains.. Speakers read the stimuli at their normal rate, half their normal rate, and as slowly as possible. In addition, a computer program paced each speaker at rates of 1, 2, and 3 syllables per second. The nasal/voice accelerometric values revealed significant stimulus effects but no rate effects. The nasality ratings of experienced listeners, evaluated as a function of stimulus and speaking rate, were compared to the accelerometric measures. The nasality scale values demonstrated small, but statistically significant, stimulus and rate effects. However, the nasality percepts were poorly correlated with the nasal/voice accelerometric measures.

The activity of N-acetyl-β-d-hexosaminidase A and B and β-glucuronidase in nasal polyps and hypertrophic nasal concha.

PubMed

Chojnowska, Sylwia; Minarowska, Alina; Waszkiewicz, Napoleon; Kępka, Alina; Zalewska-Szajda, Beata; Gościk, Elżbieta; Kowal, Krzysztof; Olszewska, Ewa; Konarzewska-Duchnowska, Emilia; Minarowski, Łukasz; Zwierz, Krzysztof; Ładny, Jerzy Robert; Szajda, Sławomir Dariusz

2014-01-01

Nasal polyps and hypertrophic lower nasal conchae are common disorders of nasal cavity. The majority of etiopathogenetic theories indicate inflammatory background of polyps and hypertrophic concha. N-acetyl-β-D-hexosaminidase and β-glucuronidase are lysosomal exoglycosidases revealing accelerated activity in inflammatory processes. The aim of the study was to evaluate the catabolism of glycoconjugates in nasal polyps and hypertrophic nasal concha basing on the activity of N-acetyl-β-D-hexosaminidase (HEX) and β-glucuronidase (GLU). Material consisted of nasal polyps taken from 40 patients during polypectomy in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and hypertrophic lower nasal conchae taken from 20 patients during mucotomy. The activity of HEX, HEX A, HEX B and GLU in supernatant of homogenates of nasal polyps and hypertrophic lower nasal concha tissues has been estimated using colorimetric method. Statistically significant decrease has been observed in concentration of the activity (per 1mg of tissue) of HEX (p<0.05), HEX B (p<0.001) and specific activity (per 1mg of protein) of HEX B (p<0.001) in nasal polyps tissue in comparison to hypertrophic lower nasal conchae tissue. Decrease in the activity and specific activity concentration of the majority of examined lysosomal exoglycosidases (increasing in inflammations) in comparison to hypertrophic lower nasal conchae suggests electrolytes disorders and questions the inflammatory background of nasal polyps. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Some engineering aspects of insulin delivery systems.

PubMed

Spencer, W J; Bair, R E; Carlson, G A; Love, J T; Urenda, R S; Eaton, R P; Schade, D S

1980-01-01

The characteristics of electronically controlled insulin delivery systems are presented. Early experiments with an external system have shown promise in providing improved glycemic control over conventional methods of single or multiple subcutaneous insulin injections. The encouraging results with external insulin delivery systems have led to the development and early testing in dogs of an implantable system with remote controls to permit variable insulin flow rates. A number of questions remain to be answered before widespread experimentation with external and implanted insulin delivery systems is possible. There appears to be no major development problems with the engineering aspects of such systems.

Use of a frameless computed tomography-guided stereotactic biopsy system for nasal biopsy in five dogs.

PubMed

Kuhlman, Gregory M; Taylor, Amanda R; Thieman-Mankin, Kelley M; Griffin, Jay; Cook, Audrey K; Levine, Jonathan M

2016-04-15

5 dogs (median age, 9 years; median body weight, 31 kg [68.2 lb]) with undefined nasal masses were examined after undergoing CT of the head and nasal biopsy via a rostral rhinoscopic or unaided (blind) approach because histologic results for collected biopsy specimens (inflammatory, necrotic, or hemorrhagic disease) suggested the specimens were nonrepresentative of the underlying disease process identified via CT (aggressive or malignant disease). Clinical signs at the time dogs were evaluated included open-mouth breathing, sneezing, or unilateral epistaxis. Histologic findings pertaining to the original biopsy specimens were suggestive of benign processes such as inflammation. In an attempt to obtain better representative specimens, a frameless CT-guided stereotactic biopsy system (CTSBS) was used to collect additional biopsy specimens from masses within the nasal and sinus passages of the dogs. The second set of biopsy specimens was histologically evaluated. Histologic evaluation of biopsy specimens collected via the CTSBS revealed results suggestive of malignant neoplasia (specifically, chondrosarcoma, hemangiopericytoma, or undifferentiated sarcoma) for 3 dogs, mild mixed-cell inflammation for 1 dog, and hamartoma for 1 dog. No complications were reported. These findings resulted in a change in treatment recommendations for 3 dogs and confirmed that no additional treatment was required for 1 dog (with hamartoma). For the remaining dog, in which CT findings and clinical history were strongly suggestive of neoplasia, the final diagnosis was rhinitis. Biopsy specimens were safely collected from masses within the nasal and sinus passages of dogs by use of a frameless CTSBS, allowing a definitive diagnosis that was unachievable with other biopsy approaches.

Anthrax Vaccine Powder Formulations for Nasal Mucosal Delivery

DTIC Science & Technology

2005-08-04

inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and...fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7–8 using trehalose as stabilizer and a CpG...gas- trointestinal, and pulmonary routes. The inhaled form is of particular concern considering its de- monstrated use as a bioweapon.1–4 Inhalational

Nasal microenvironments and interspecific interactions influence nasal microbiota complexity and S. aureus carriage.

PubMed

Yan, Miling; Pamp, Sünje J; Fukuyama, Julia; Hwang, Peter H; Cho, Do-Yeon; Holmes, Susan; Relman, David A

2013-12-11

The indigenous microbiota of the nasal cavity plays important roles in human health and disease. Patterns of spatial variation in microbiota composition may help explain Staphylococcus aureus colonization and reveal interspecies and species-host interactions. To assess the biogeography of the nasal microbiota, we sampled healthy subjects, representing both S. aureus carriers and noncarriers at three nasal sites (anterior naris, middle meatus, and sphenoethmoidal recess). Phylogenetic compositional and sparse linear discriminant analyses revealed communities that differed according to site epithelium type and S. aureus culture-based carriage status. Corynebacterium accolens and C. pseudodiphtheriticum were identified as the most important microbial community determinants of S. aureus carriage, and competitive interactions were only evident at sites with ciliated pseudostratified columnar epithelium. In vitro cocultivation experiments provided supporting evidence of interactions among these species. These results highlight spatial variation in nasal microbial communities and differences in community composition between S. aureus carriers and noncarriers. Copyright © 2013 Elsevier Inc. All rights reserved.

Nasal microenvironments and interspecific interactions influence nasal microbiota complexity and S. aureus carriage

PubMed Central

Yan, Miling; Pamp, Sünje J.; Fukuyama, Julia; Hwang, Peter H.; Cho, Do-Yeon; Holmes, Susan; Relman, David A.

2013-01-01

Summary The indigenous microbiota of the nasal cavity plays important roles in human health and disease. Patterns of spatial variation in microbiota composition may help explain Staphylococcus aureus colonization, and reveal interspecies and species-host interactions. To assess the biogeography of the nasal microbiota, we sampled healthy subjects, representing both S. aureus carriers and non-carriers, at 3 nasal sites (anterior naris, middle meatus, and sphenoethmoidal recess). Phylogenetic compositional and sparse linear discriminant analyses revealed communities that differed according to site epithelium type and S. aureus culture-based carriage status. Corynebacterium accolens and C. pseudodiphtheriticum were identified as the most important microbial community determinants of S. aureus carriage, with competitive interactions evident only at sites with ciliated pseudostratified columnar epithelium. In vitro co-cultivation experiments provided supporting evidence of interactions among these species. These results highlight spatial variation in nasal microbial communities and differences in community composition between S. aureus carriers and non-carriers. PMID:24331461

Micro injector sample delivery system for charged molecules

DOEpatents

Davidson, James C.; Balch, Joseph W.

1999-11-09

A micro injector sample delivery system for charged molecules. The injector is used for collecting and delivering controlled amounts of charged molecule samples for subsequent analysis. The injector delivery system can be scaled to large numbers (>96) for sample delivery to massively parallel high throughput analysis systems. The essence of the injector system is an electric field controllable loading tip including a section of porous material. By applying the appropriate polarity bias potential to the injector tip, charged molecules will migrate into porous material, and by reversing the polarity bias potential the molecules are ejected or forced away from the tip. The invention has application for uptake of charged biological molecules (e.g. proteins, nucleic acids, polymers, etc.) for delivery to analytical systems, and can be used in automated sample delivery systems.

Simulating the nasal cycle with computational fluid dynamics

PubMed Central

Patel, Ruchin G.; Garcia, Guilherme J. M.; Frank-Ito, Dennis O.; Kimbell, Julia S.; Rhee, John S.

2015-01-01

Objectives (1) Develop a method to account for the confounding effect of the nasal cycle when comparing pre- and post-surgery objective measures of nasal patency. (2) Illustrate this method by reporting objective measures derived from computational fluid dynamics (CFD) models spanning the full range of mucosal engorgement associated with the nasal cycle in two subjects. Study Design Retrospective Setting Academic tertiary medical center. Subjects and Methods A cohort of 24 nasal airway obstruction patients was reviewed to select the two patients with the greatest reciprocal change in mucosal engorgement between pre- and post-surgery computed tomography (CT) scans. Three-dimensional anatomic models were created based on the pre- and post-operative CT scans. Nasal cycling models were also created by gradually changing the thickness of the inferior turbinate, middle turbinate, and septal swell body. CFD was used to simulate airflow and to calculate nasal resistance and average heat flux. Results Before accounting for the nasal cycle, Patient A appeared to have a paradoxical worsening nasal obstruction in the right cavity postoperatively. After accounting for the nasal cycle, Patient A had small improvements in objective measures postoperatively. The magnitude of the surgical effect also differed in Patient B after accounting for the nasal cycle. Conclusion By simulating the nasal cycle and comparing models in similar congestive states, surgical changes in nasal patency can be distinguished from physiological changes associated with the nasal cycle. This ability can lead to more precise comparisons of pre and post-surgery objective measures and potentially more accurate virtual surgery planning. PMID:25450411

[Clinical analysis of nasal mucosa contact headache].

PubMed

Gu, Qingjia; Wen, Bei; Li, Jingxian; Fan, Jiangang; He, Gang

2013-07-01

To investigate the efficacy of nasal mucosa contact point headache with the treatment of endoscopic sinus surgery. Clinical data of 75 cases with nasal mucosa contact point headache treated in our department from Jan 2008 to Nov 2011 were retrospectively analyzed. These patients were performed with endoscopic sinus surgery. All patients were followed up for more than six months. They all achieved significant efficacy and no complications occurred. Nasal mucosa contact point headache and primary headache had different clinical features and different treatment. Misdiagnosis were easily made if not being carefully analyzed. Three lines tension relaxing septorhinoplasty combined with nasal bone fracture correction can achieve satisfactory curative effect and can effectively prevent the occurrence of complications. Therefore, it is necessary to strengthen the awareness of this disease. Nasal structure abnormality is the main reason of nasal mucosa contact point headache. The implementation of individualized nasal endoscopic sinus surgery can achieve satisfactory curative effect.

Smart Drug Delivery Systems in Cancer Therapy.

PubMed

Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fiber laser coupled optical spark delivery system

DOEpatents

Yalin, Azer [Fort Collins, CO; Willson, Bryan [Fort Collins, CO; Defoort, Morgan [Fort Collins, CO; Joshi, Sachin [Fort Collins, CO; Reynolds, Adam [Fort Collins, CO

2008-03-04

A spark delivery system for generating a spark using a laser beam is provided, and includes a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. The laser delivery assembly further includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. Other embodiments use a fiber laser to generate a spark. Embodiments of the present invention may be used to create a spark in an engine. Yet other embodiments include collecting light from the spark or a flame resulting from the spark and conveying the light for diagnostics. Methods of using the spark delivery systems and diagnostic systems are provided.

The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery.

PubMed

Shorter, Susan A; Gollings, Alexander S; Gorringe-Pattrick, Monique A M; Coakley, J Emma; Dyer, Paul D R; Richardson, Simon C W

2017-05-01

The potential of gene replacement therapy has been underscored by the market authorization of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for 'drug' delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the 'PEG dilemma', balancing toxicity and limited (often liver-tropic) pharmacokinetics/oharmacodynamics, with the membrane destabilizing activity, necessary for nucleocytosolic access and transfection remain a problem. Areas covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG dilemma, and their biological properties with specific reference to their intracellular trafficking. Expert opinion: The possibility of using attenuated toxins as antisense and siRNA delivery systems has been demonstrated in vitro. Systems based upon attenuated anthrax toxin have been shown to have high activity (equivalent to nucleofection) and low toxicity whilst not requiring cationic 'helpers' or condensing agents, divorcing these systems from the problems associated with the PEG dilemma. It remains to be seen whether these systems can operate safely, efficiently and reproducibly, in vivo or in the clinic.

Permeation and Systemic Absorption of R- and S-Baclofen across the Nasal Mucosa

PubMed Central

Zhang, Hefei; Schmidt, Mark; Murry, Daryl J.; Donovan, Maureen D.

2012-01-01

Baclofen, an antispasmodic agent that acts as a GABAB agonist, resembles phenylalanine in structure and has been reported to be a substrate of the large amino acid transporter, LAT-1. The objective of this study was to investigate the absorption of baclofen across the nasal mucosa both in vitro and in vivo. Baclofen transport was measured across excised bovine olfactory and respiratory mucosae to investigate site-specific uptake of baclofen, and the intranasal bioavailability of R- and S- baclofen was determined in rats. Increasing flux with increasing baclofen donor concentration and the absence of polarized transport was observed in vitro and similar distribution profiles were observed for both enantiomers following intranasal administration in rats. The absence of stereospecificity in nasal absorption indicates limited involvement of the amino acid or other transporters in the nasal absorption of baclofen. PMID:21283988

Distinct immune responses and virus shedding in pigs following aerosol, intra-nasal and contact infection with pandemic swine influenza A virus, A(H1N1)09.

PubMed

Hemmink, Johanneke D; Morgan, Sophie B; Aramouni, Mario; Everett, Helen; Salguero, Francisco J; Canini, Laetitia; Porter, Emily; Chase-Topping, Margo; Beck, Katy; Loughlin, Ronan Mac; Carr, B Veronica; Brown, Ian H; Bailey, Mick; Woolhouse, Mark; Brookes, Sharon M; Charleston, Bryan; Tchilian, Elma

2016-10-20

Influenza virus infection in pigs is a major farming problem, causing considerable economic loss and posing a zoonotic threat. In addition the pig is an excellent model for understanding immunity to influenza viruses as this is a natural host pathogen system. Experimentally, influenza virus is delivered to pigs intra-nasally, by intra-tracheal instillation or by aerosol, but there is little data comparing the outcome of different methods. We evaluated the shedding pattern, cytokine responses in nasal swabs and immune responses following delivery of low or high dose swine influenza pdmH1N1 virus to the respiratory tract of pigs intra-nasally or by aerosol and compared them to those induced in naturally infected contact pigs. Our data shows that natural infection by contact induces remarkably high innate and adaptive immune response, although the animals were exposed to a very low virus dose. In contacts, the kinetics of virus shedding were slow and prolonged and more similar to the low dose directly infected animals. In contrast the cytokine profile in nasal swabs, antibody and cellular immune responses of contacts more closely resemble immune responses in high dose directly inoculated animals. Consideration of these differences is important for studies of disease pathogenesis and assessment of vaccine protective efficacy.

Status of Statewide Career Information Delivery Systems.

ERIC Educational Resources Information Center

Dunn, Wynonia L.

Intended as a resource document as well as a status report on all the statewide career information delivery systems (CIDS) in operation, this report examines the status of 39 statewide information systems. (Career information delivery systems are computer-based systems that provide national, state, and local information to individuals who are in…

Planetary Regolith Delivery Systems for ISRU

NASA Technical Reports Server (NTRS)

Mantovani, James G.; Townsend, Ivan I., III

2012-01-01

The challenges associated with collecting regolith on a planetary surface and delivering it to an in-situ resource utilization system differ significantly from similar activities conducted on Earth. Since system maintenance on a planetary body can be difficult or impossible to do, high reliability and service life are expected of a regolith delivery system. Mission costs impose upper limits on power and mass. The regolith delivery system must provide a leak-tight interface between the near-vacuum planetary surface and the pressurized ISRU system. Regolith delivery in amounts ranging from a few grams to tens of kilograms may be required. Finally, the spent regolith must be removed from the ISRU chamber and returned to the planetary environment via dust tolerant valves capable of operating and sealing over a large temperature range. This paper will describe pneumatic and auger regolith transfer systems that have already been field tested for ISRU, and discuss other systems that await future field testing.

Delayed extubation to nasal continuous positive airway pressure in the immature baboon model of bronchopulmonary dysplasia: lung clinical and pathological findings.

PubMed

Thomson, Merran A; Yoder, Bradley A; Winter, Vicki T; Giavedoni, Luis; Chang, Ling Yi; Coalson, Jacqueline J

2006-11-01

Using the 125-day baboon model of bronchopulmonary dysplasia treated with prenatal steroid and exogenous surfactant, we hypothesized that a delay of extubation from low tidal volume positive pressure ventilation to nasal continuous positive airway pressure at 5 days (delayed nasal continuous positive airway pressure group) would not induce more lung injury when compared with baboons aggressively weaned to nasal continuous positive airway pressure at 24 hours (early nasal continuous positive airway pressure group), because both received positive pressure ventilation. After delivery by cesarean section at 125 days (term: 185 days), infants received 2 doses of Curosurf (Chiesi Farmaceutica S.p.A., Parma, Italy) and daily caffeine citrate. The delay in extubation to 5 days resulted in baboons in the delayed nasal continuous positive airway pressure group having a lower arterial to alveolar oxygen ratio, high PaCO2, and worse respiratory function. The animals in the delayed nasal continuous positive airway pressure group exhibited a poor respiratory drive that contributed to more reintubations and time on mechanical ventilation. A few animals in both groups developed necrotizing enterocolitis and/or sepsis, but infectious pneumonias were not documented. Cellular bronchiolitis and peribronchiolar alveolar wall thickening were more frequently seen in the delayed nasal continuous positive airway pressure group. Bronchoalveolar lavage levels of interleukin-6, interleukin-8, monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha, and growth-regulated oncogene-alpha were significantly increased in the delayed nasal continuous positive airway pressure group. Standard and digital morphometric analyses showed no significant differences in internal surface area and nodal measurements between the groups. Platelet endothelial cell adhesion molecule vascular staining was not significantly different between the 2 nasal continuous positive airway pressure groups

Methods and metrics challenges of delivery-system research

PubMed Central

2012-01-01

Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned). This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not) into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1) modeling intervention context; (2) measuring readiness for change; (3) assessing intervention fidelity and sustainability; (4) assessing complex, multicomponent interventions; and (5) incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory) and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on February 16-17, 2011

Modeling the Delivery Physiology of Distributed Learning Systems.

ERIC Educational Resources Information Center

Paquette, Gilbert; Rosca, Ioan

2003-01-01

Discusses instructional delivery models and their physiology in distributed learning systems. Highlights include building delivery models; types of delivery models, including distributed classroom, self-training on the Web, online training, communities of practice, and performance support systems; and actors (users) involved, including experts,…

A laser device for fusion of nasal mucosa

NASA Astrophysics Data System (ADS)

Sooklal, Valmiki; McClure, Jesse; Hooper, Luke; Larson, Michael

2010-02-01

A prototype device has been created to fuse septal tissue membranes as an alternative to sutures or staples through the controlled application of laser heating and pressure to induce protein denaturation and subsequent tissue fusion, through renaturation and intertwining, across the interface. Lasers have been used to close wounds in controlled laboratory tests over the last 15 years. Many encouraging results have been obtained; however, no commercial delivery systems are currently available. This is due primarily to two factors: requiring an inordinate amount of experience on the part of the operator, and attempting to achieve general applicability for multiple tissue systems. The present device overcomes these barriers as it is tailored for the particular application of septal laser fusion, namely for the coaptation of mucoperichondrial membranes. The important parameters involved in fusing biological tissues are identified. The development of the device followed from computational modeling based on Monte Carlo simulation of photon transport and on engineering firstprinciples. Experiments were designed and analyzed using orthogonal arrays, employing a subset of the relevant parameters, i.e., laser irradiance, dwell time and spot size, for a range of wavelengths. The in vitro fusion experiments employed 1cm by 1cm sections of equine nasal mucosa having a nominal thickness of 1mm.

Numerical simulation and nasal air-conditioning

PubMed Central

Keck, Tilman; Lindemann, Jörg

2011-01-01

Heating and humidification of the respiratory air are the main functions of the nasal airways in addition to cleansing and olfaction. Optimal nasal air conditioning is mandatory for an ideal pulmonary gas exchange in order to avoid desiccation and adhesion of the alveolar capillary bed. The complex three-dimensional anatomical structure of the nose makes it impossible to perform detailed in vivo studies on intranasal heating and humidification within the entire nasal airways applying various technical set-ups. The main problem of in vivo temperature and humidity measurements is a poor spatial and time resolution. Therefore, in vivo measurements are feasible only to a restricted extent, solely providing single temperature values as the complete nose is not entirely accessible. Therefore, data on the overall performance of the nose are only based on one single measurement within each nasal segment. In vivo measurements within the entire nose are not feasible. These serious technical issues concerning in vivo measurements led to a large number of numerical simulation projects in the last few years providing novel information about the complex functions of the nasal airways. In general, numerical simulations merely calculate predictions in a computational model, e.g. a realistic nose model, depending on the setting of the boundary conditions. Therefore, numerical simulations achieve only approximations of a possible real situation. The aim of this review is the synopsis of the technical expertise on the field of in vivo nasal air conditioning, the novel information of numerical simulations and the current state of knowledge on the influence of nasal and sinus surgery on nasal air conditioning. PMID:22073112

A new approach to the treatment of nasal bone fracture: radiologic classification of nasal bone fractures and its clinical application.

PubMed

Han, Daniel Seung Youl; Han, Yea Sik; Park, Jin Hyung

2011-11-01

A radiologic examination is required in the treatment of nasal bone fracture to determine the fracture condition. Thus, there is an increasing need for radiologic classification of nasal bone fractures that can be applied to clinical practice. Computed tomography was performed in 125 patients with nasal bone fractures to determine which axial view best showed the entire nasal view. The obtained axial view was then used as a reference for classification. The length from the top to the base of the nasal bone was divided into upper, middle, and lower levels, after which the fracture location was determined. If the fracture spanned the boundaries of these levels, it was classified as the total level. Subsequently, the fracture was subclassified based on the fracture direction and pattern and the concurrent fracture. Radiologic examination of patients with nasal bone fracture showed that nasal bone fracture was frequently found at the total, middle, upper, and lower levels, in that order. Nasal bone fractures at the upper level showed lower frequencies of complication and reoperation than the fractures at the other levels, whereas nasal bone fractures at the total level showed the highest frequencies of complication and reoperation. Radiologic classification can be useful for preoperative and postoperative evaluations of nasal bone fractures and can be helpful in understanding such fractures because it can efficiently predict the prognosis of a fracture. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Nasal and Oral Inspiration During Natural Speech Breathing

PubMed Central

Lester, Rosemary A.; Hoit, Jeannette D.

2015-01-01

Purpose The purpose of this study was to determine the typical pattern for inspiration during speech breathing in healthy adults, as well as the factors that might influence it. Method Ten healthy adults, 18–45 years of age, performed a variety of speaking tasks while nasal ram pressure, audio, and video recordings were obtained. Inspirations were categorized as a nasal only, oral only, simultaneous nasal and oral, or alternating nasal and oral inspiration. The method was validated using nasal airflow, oral airflow, audio, and video recordings for two participants. Results The predominant pattern was simultaneous nasal and oral inspirations for all speaking tasks. This pattern was not affected by the nature of the speaking task or by the phonetic context surrounding the inspiration. The validation procedure confirmed that nearly all inspirations during counting and paragraph reading were simultaneous nasal and oral inspirations; whereas for sentence reading, the predominant pattern was alternating nasal and oral inspirations across the three phonetic contexts. Conclusions Healthy adults inspire through both the nose and mouth during natural speech breathing. This pattern of inspiration is likely beneficial in reducing pathway resistance while preserving some of the benefits of nasal breathing. PMID:24129013

Silk-based delivery systems of bioactive molecules

PubMed Central

Numata, Keiji; Kaplan, David L

2010-01-01

Silks are biodegradable, biocompatible, self-assemblying proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes are reviewed. PMID:20298729

Advanced Drug Delivery Systems for Transdermal Delivery of Non-Steroidal Anti-Inflammatory Drugs: A Review.

PubMed

Kumar, Lalit; Verma, Shivani; Singh, Mehakjot; Tamanna, Tamanna; Utreja, Puneet

2018-06-04

Transdermal route of delivery of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) has several advantages over other routes like reduced adverse effects, less systemic absorption, and avoidance of first pass effect and degradation in the gastrointestinal tract (GIT). Transdermal route is also beneficial for drugs having a narrow therapeutic index. The skin acts as the primary barrier for transdermal delivery of various therapeutic molecules. Various advanced nanocarrier systems offer several advantages like improved dermal penetration along with an extended drug release profile due to their smaller size and high surface area. Various nanocarrier explored for transdermal delivery of NSAIDs are liposomes, niosomes, ethosomes, polymeric nanoparticles (NPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), dendrimers, nanosuspensions/nanoemulsion, and nanofibers Objectives: In the present review, our major aim was to explore the therapeutic potential of advanced nanocarrier systems enlisted above for transdermal delivery of NSAIDs. All literature search regarding advanced nanocarrier systems for transdermal delivery of NSAIDs was done using Google Scholar and Pubmed. Advanced nanocarrier have shown various advantages like reduced side effect, low dosing frequency, high skin permeation, and ease of application over conventional transdermal delivery systems of NSAIDs in various preclinical studies. However, clinical exploration of advanced nanocarrier systems for transdermal delivery of NSAIDs is still a challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Clinical symptoms and immunology inspection characteristics of nasal cavity local allergy].

PubMed

Yin, Z X; Zhu, Y; Zhai, X; Zhang, J L; Liu, G

2017-08-05

were positive, could be diagnosised as local allergic rhinitis. After three years, all of the observation group patients were detected with SPT and serum allergen SIgE test. Five patients diagnosed as local allergic rhinitis before three years were positive. Six patients diagnosed as NAR before three years were negative. Conclusion: For patients with the typical medical history and symptoms of AR, but allergen SPT and serum allergen SIgE test were negative, there was local specific hypersensitivity in nasal mucosa, but the reaction was not accompanied by systemic sensitization. Combined with nasal secretions allergen SIgE test or allergen nasal mucosa proocation tests positive, could be diagnosed as local allergic rhinitis. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Mucoadhesive and thermogelling systems for vaginal drug delivery.

PubMed

Caramella, Carla M; Rossi, Silvia; Ferrari, Franca; Bonferoni, Maria Cristina; Sandri, Giuseppina

2015-09-15

This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described. Copyright © 2015 Elsevier B.V. All rights reserved.

Oronasal Masks Require a Higher Pressure than Nasal and Nasal Pillow Masks for the Treatment of Obstructive Sleep Apnea

PubMed Central

Deshpande, Sheetal; Joosten, Simon; Turton, Anthony; Edwards, Bradley A.; Landry, Shane; Mansfield, Darren R.; Hamilton, Garun S.

2016-01-01

Study Objectives: Oronasal masks are frequently used for continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). The aim of this study was to (1) determine if CPAP requirements are higher for oronasal masks compared to nasal mask interfaces and (2) assess whether polysomnography and patient characteristics differed among mask preference groups. Methods: Retrospective analysis of all CPAP implementation polysomnograms between July 2013 and June 2014. Prescribed CPAP level, polysomnography results and patient data were compared according to mask type (n = 358). Results: Oronasal masks were used in 46%, nasal masks in 35% and nasal pillow masks in 19%. There was no difference according to mask type for baseline apnea-hypopnea index (AHI), body mass index (BMI), waist or neck circumference. CPAP level was higher for oronasal masks, 12 (10–15.5) cm H2O compared to nasal pillow masks, 11 (8–12.5) cm H2O and nasal masks, 10 (8–12) cm H2O, p < 0.0001 (Median [interquartile range]). Oronasal mask type, AHI, age, and BMI were independent predictors of a higher CPAP pressure (p < 0.0005, adjusted R2 = 0.26.). For patients with CPAP ≥ 15 cm H2O, there was an odds ratio of 4.5 (95% CI 2.5–8.0) for having an oronasal compared to a nasal or nasal pillow mask. Residual median AHI was higher for oronasal masks (11.3 events/h) than for nasal masks (6.4 events/h) and nasal pillows (6.7 events/h), p < 0.001. Conclusions: Compared to nasal mask types, oronasal masks are associated with higher CPAP pressures (particularly pressures ≥ 15 cm H2O) and a higher residual AHI. Further evaluation with a randomized control trial is required to definitively establish the effect of mask type on pressure requirements. Commentary: A commentary on this article appears in this issue on page 1209. Citation: Deshpande S, Joosten S, Turton A, Edwards BA, Landry S, Mansfield DR, Hamilton GS. Oronasal masks require a higher pressure than nasal and

Phenotype and function of nasal dendritic cells

PubMed Central

Lee, Haekyung; Ruane, Darren; Law, Kenneth; Ho, Yan; Garg, Aakash; Rahman, Adeeb; Esterházy, Daria; Cheong, Cheolho; Goljo, Erden; Sikora, Andrew G.; Mucida, Daniel; Chen, Benjamin; Govindraj, Satish; Breton, Gaëlle; Mehandru, Saurabh

2015-01-01

Intranasal vaccination generates immunity across local, regional and distant sites. However, nasal dendritic cells (DC), pivotal for the induction of intranasal vaccine- induced immune responses, have not been studied in detail. Here, using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of “classical” DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were FLT3 ligand-responsive and displayed unique phenotypic and functional characteristics including the ability to present antigen, induce an allogeneic T cell response and migrate in response to LPS or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1+ DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1+ and BDCA-3hi DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic and functional properties of nasal DCs and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis. PMID:25669151

Nasal Morphology of the Chinese: Three-Dimensional Reference Values for Rhinoplasty.

PubMed

Jayaratne, Yasas S N; Deutsch, Curtis K; Zwahlen, Roger A

2014-06-01

To determine normative nasal measurements for Chinese young adults, conditioned on demographics. A cross-sectional descriptive study. A university hospital. Three-dimensional (3D) photographs were captured from 103 Chinese subjects between 18 and 35 years of age using a commercial stereophotographic system. Anthropometric landmarks were identified on these 3D surface images, and measurements suitable for nasal analysis were performed and contrasted against established Caucasian norms. Gender differences in anthropometric dimensions were also analyzed. Normative data for these measurements are made available. Linear nasal measurements, except those for mid-columella length, were significantly larger in men than in women; further, the nasal tip angle and nasofrontal angle were significantly larger in Chinese women. Contrasts of these new data against published Caucasian norms revealed dimensions that differ for these 2 groups. The Chinese normative mean values for morphological nose width, nasal tip angle, nasofrontal angle, and alar slope angle exceeded those reported for North American Caucasians. Gender-specific normative data for the Chinese nose were established in this study to provide a useful tool for surgeons in dealing with rhinoplasty. Moreover, the Chinese nasal anthropometric measurements in this study are broader and flatter than those reported for North American Caucasians. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Regional deposition of mometasone furoate nasal spray suspension in humans.

PubMed

Shah, Samir A; Berger, Robert L; McDermott, John; Gupta, Pranav; Monteith, David; Connor, Alyson; Lin, Wu

2015-01-01

Nasal deposition studies can demonstrate whether nasal sprays treating allergic rhinitis and polyposis reach the ciliated posterior nasal cavity, where turbinate inflammation and other pathology occurs. However, quantifying nasal deposition is challenging, because in vitro tests do not correlate to human nasal deposition; gamma scintigraphy studies are thus used. For valid data, the radiolabel must distribute, as the drug, into different-sized droplets, remain associated with the drug in the formulation after administration, and not alter its deposition. Some nasal deposition studies have demonstrated this using homogenous solutions. However, most commercial nasal sprays are heterogeneous suspensions. Using mometasone furoate nasal suspension (MFS), we developed a technique to validate radiolabel deposition as a surrogate for nasal cavity drug deposition and characterized regional deposition and nasal clearance in humans. Mometasone furoate (MF) formulation was spiked with diethylene triamine pentacaetic acid. Both unlabeled and radiolabeled formulations (n = 3) were sprayed into a regionally divided nasal cast. Drug deposition was quantified by high pressure liquid chromatography within each region; radiolabel deposition was determined by gamma camera. Healthy subjects (n = 12) were dosed and imaged for six hours. Scintigraphic images were coregistered with magnetic resonance imaging scans to quantify anterior and posterior nasal cavity deposition and mucociliary clearance. The ratio of radiolabel to unlabeled drug was 1.05 in the nasal cast and regionally appeared to match, indicating that in vivo radiolabel deposition could represent drug deposition. In humans, MFS delivered 86% (9.2) of metered dose to the nasal cavity, approximately 60% (9.1) of metered dose to the posterior nasal cavity. After 15 minutes, mucociliary clearance removed 59% of the initial radiolabel in the nasal cavity, consistent with clearance rates from the ciliated posterior surface. MFS

Regional deposition of mometasone furoate nasal spray suspension in humans.

PubMed

Shah, S A; Berger, R L; McDermott, J; Gupta, P; Monteith, D; Connor, A; Lin, W

2014-11-21

Nasal deposition studies can demonstrate whether nasal sprays treating allergic rhinitis and polyposis reach the ciliated posterior nasal cavity, where turbinate inflammation and other pathology occurs. However, quantifying nasal deposition is challenging, because in vitro tests do not correlate to human nasal deposition; gamma scintigraphy studies are thus used. For valid data, the radiolabel must distribute, as the drug, into different-sized droplets, remain associated with the drug in the formulation after administration, and not alter its deposition. Some nasal deposition studies have demonstrated this using homogenous solutions. However, most commercial nasal sprays are heterogeneous suspensions. Using mometasone furoate nasal suspension (MFS), we developed a technique to validate radiolabel deposition as a surrogate for nasal cavity drug deposition and characterized regional deposition and nasal clearance in humans. Mometasone furoate (MF) formulation was spiked with diethylene triamine pentacaetic acid. Both unlabeled and radiolabeled formulations (n = 3) were sprayed into a regionally divided nasal cast. Drug deposition was quantified by high pressure liquid chromatography within each region; radiolabel deposition was determined by gamma camera. Healthy subjects (n = 12) were dosed and imaged for six hours. Scintigraphic images were coregistered with magnetic resonance imaging scans to quantify anterior and posterior nasal cavity deposition and mucociliary clearance. The ratio of radiolabel to unlabeled drug was 1.05 in the nasal cast and regionally appeared to match, indicating that in vivo radiolabel deposition could represent drug deposition. In humans, MFS delivered 86% (9.2) of metered dose to the nasal cavity, approximately 60% (9.1) of metered dose to the posterior nasal cavity. After 15 minutes, mucociliary clearance removed 59% of the initial radiolabel in the nasal cavity, consistent with clearance rates from the ciliated posterior surface. MFS

A Cost-Effectiveness Analysis of Nasal Surgery to Increase Continuous Positive Airway Pressure Adherence in Sleep Apnea Patients With Nasal Obstruction

PubMed Central

Kempfle, Judith S.; BuSaba, Nicholas Y.; Dobrowski, John M.; Westover, Michael B.; Bianchi, Matt T.

2017-01-01

Objectives/Hypothesis Nasal surgery has been implicated to improve continuous positive airway pressure (CPAP) compliance in patients with obstructive sleep apnea (OSA) and nasal obstruction. However, the cost-effectiveness of nasal surgery to improve CPAP compliance is not known. We modeled the cost-effectiveness of two types of nasal surgery versus no surgery in patients with OSA and nasal obstruction undergoing CPAP therapy. Study Design Cost-effectiveness decision tree model. Methods We built a decision tree model to identify conditions under which nasal surgery would be cost-effective to improve CPAP adherence over the standard of care. We compared turbinate reduction and septoplasty to nonsurgical treatment over varied time horizons from a third-party payer perspective. We included variables for cost of untreated OSA, surgical cost and complications, improved compliance postoperatively, and quality of life. Results Our study identified nasal surgery as a cost-effective strategy to improve compliance of OSA patients using CPAP across a range of plausible model assumptions regarding the cost of untreated OSA, the probability of adherence improvement, and a chronic time horizon. The relatively lower surgical cost of turbinate reduction made it more cost-effective at earlier time horizons, whereas septoplasty became cost-effective after a longer timespan. Conclusions Across a range of plausible values in a clinically relevant decision model, nasal surgery is a cost-effective strategy to improve CPAP compliance in OSA patients with nasal obstruction. Our results suggest that OSA patients with nasal obstruction who struggle with CPAP therapy compliance should undergo evaluation for nasal surgery. PMID:27653626

Silk-based delivery systems of bioactive molecules.

PubMed

Numata, Keiji; Kaplan, David L

2010-12-30

Silks are biodegradable, biocompatible, self-assembling proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes is reviewed. Copyright © 2010 Elsevier B.V. All rights reserved.

Nasal Chondromesenchymal Hamartoma in a Child

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finitsis, Stefanos; Giavroglou, Constantinos; Potsi, Stamatia, E-mail: matinapotsi@hotmail.co

Nasal chondromesenchymal hamartoma (NCMH) is a benign tumor that was described in 1998. The occurrence of this lesion in the nasal cavity of infants and children is especially rare, with only 21 cases reported in the international literature. We report a 12-month-old boy with respiratory distress due to nasal obstruction. Computed tomographic scan and magnetic resonance imaging examination demonstrated a soft-tissue mass obstructing the left nasal cavity. Digital subtraction angiography and preoperative superselective embolization with microparticles were also performed. The tumor was completely resected surgically. Histopathology and immunohistochemical analyses of the tumor disclosed a NCMH. The imaging characteristics of themore » tumor are described and the radiology literature is reviewed.« less

Advances in bioresponsive closed-loop drug delivery systems.

PubMed

Yu, Jicheng; Zhang, Yuqi; Yan, Junjie; Kahkoska, Anna R; Gu, Zhen

2017-11-27

Controlled drug delivery systems are able to improve efficacy and safety of therapeutics by optimizing the duration and kinetics of release. Among them, closed-loop delivery strategies, also known as self-regulated administration, have proven to be a practical tool for homeostatic regulation, by tuning drug release as a function of biosignals relevant to physiological and pathological processes. A typical example is glucose-responsive insulin delivery system, which can mimic the pancreatic beta cells to release insulin with a proper dose at a proper time point by responding to plasma glucose levels. Similar self-regulated systems are also important in the treatment of other diseases including thrombosis and bacterial infection. In this review, we survey the recent advances in bioresponsive closed-loop drug delivery systems, including glucose-responsive, enzyme-activated, and other biosignal-mediated delivery systems. We also discuss the future opportunities and challenges in this field. Copyright © 2017 Elsevier B.V. All rights reserved.

Advances of blood cell-based drug delivery systems.

PubMed

Sun, Yanan; Su, Jing; Liu, Geyi; Chen, Jianjun; Zhang, Xiumei; Zhang, Ran; Jiang, Minhan; Qiu, Mingfeng

2017-01-01

Blood cells, including erythrocytes, leukocytes and platelets are used as drug carriers in a wide range of applications. They have many unique advantages such as long life-span in circulation (especially erythrocytes), target release capacities (especially platelets), and natural adhesive properties (leukocytes and platelets). These properties make blood cell based delivery systems, as well as their membrane-derived carriers, far superior to other drug delivery systems. Despite the advantages, the further development of blood cell-based delivery systems was hindered by limitations in the source, storage, and mass production. To overcome these problems, synthetic biomaterials that mimic blood cell and nanocrystallization of blood cells have been developed and may represent the future direction for blood cell membrane-based delivery systems. In this paper, we review recent progress of the rising blood cell-based drug delivery systems, and also discuss their challenges and future tendency of development. Copyright © 2016. Published by Elsevier B.V.

Assessment of the effect of deviated nasal septum on the structure of nasal cavity.

PubMed

Wang, Junguo; Dou, Xin; Liu, Dingding; Song, Panpan; Qian, Xiaoyun; Wang, Shoulin; Gao, Xia

2016-06-01

The present study was aimed to investigate the effects of DNS on the structure of nasal cavity. The paranasal sinus coronal view CT of 108 patients with DNS and 129 hospitalized patients without DNS was retrospectively analyzed. The transverse diameter of nasal cavity (a), transverse diameter of nasal cavity and paranasal sinus (b), angle between maxillary and palatal bone, interalveolar distance, and maxillary rotation distance were measured. The ratio of a/b in experimental group was 0.367 ± 0.006 which was significantly (P = 0.0023) less than that in control group (0.391 ± 0.005). For the angle between maxillary and palatal bone, there was no significant difference found between DNS and control group for both right and left sides. The interalveolar distance was 40.75 mm in experimental group, and 38.8 mm in control (P = 0.0002). For the maxillary rotation distance, findings were considered as significant (P < 0.0001) in experimental group (11.25 mm) compared with control (10.1 mm). The present study demonstrates that long-term DNS affects the development of nasal cavity and paranasal sinus, as well as increases the interalveolar distance and maxillary rotation distance. These influences may be caused by the alteration of airflow inside the nasal cavities.

Nasal Duplication Combined with Cleft Lip and Palate: Surgical Correction and Long-Term Follow-Up.

PubMed

Long, Kanharith; Yamaguchi, Kazuaki; Lonic, Daniel; Long, Vanna; Chhoeurn, Vuthy; Lo, Lun-Jou

2017-10-01

Diprosopus dirrhinus, or nasal duplication, is a rare entity of partial craniofacial duplication. The case we present is the first report of diprosopus dirrhinus associated with complete cleft lip and palate. The baby was born in Cambodia at full term by normal vaginal delivery with no significant perinatal and family history. Physical examination revealed significant facial deformity due to the duplicated nose and the left complete cleft lip/palate on the right subset. There were 4 nostrils; both medial apertures including the cleft site were found to be 10-15 mm deep cul-de-sac structures without communication to the nasopharynx. The upper third of the face was notable for hypertelorism with a duplication of the soft-tissue nasion and glabella. Between the 2 nasal dorsums, there was a small cutaneous depression with a lacrimal fistula in the midline. Surgical treatment included the first stage of primary lip and nose repair and the second stage of palatoplasty. The patient was followed up at the age of 10 years showing satisfactory results for both aesthetic and functional aspects. Further management in the future will be required for the hypertelorism and nasal deformity.

Nasal Duplication Combined with Cleft Lip and Palate: Surgical Correction and Long-Term Follow-Up

PubMed Central

Long, Kanharith; Yamaguchi, Kazuaki; Lonic, Daniel; Long, Vanna; Chhoeurn, Vuthy

2017-01-01

Background: Diprosopus dirrhinus, or nasal duplication, is a rare entity of partial craniofacial duplication. Methods: The case we present is the first report of diprosopus dirrhinus associated with complete cleft lip and palate. The baby was born in Cambodia at full term by normal vaginal delivery with no significant perinatal and family history. Physical examination revealed significant facial deformity due to the duplicated nose and the left complete cleft lip/palate on the right subset. Results: There were 4 nostrils; both medial apertures including the cleft site were found to be 10–15 mm deep cul-de-sac structures without communication to the nasopharynx. The upper third of the face was notable for hypertelorism with a duplication of the soft-tissue nasion and glabella. Between the 2 nasal dorsums, there was a small cutaneous depression with a lacrimal fistula in the midline. Surgical treatment included the first stage of primary lip and nose repair and the second stage of palatoplasty. Conclusions: The patient was followed up at the age of 10 years showing satisfactory results for both aesthetic and functional aspects. Further management in the future will be required for the hypertelorism and nasal deformity. PMID:29184738

Incorporating a Nebulizer System Into High-Flow Nasal Cannula Improves Comfort in Infants With Bronchiolitis.

PubMed

Valencia-Ramos, Juan; Mirás, Alicia; Cilla, Amacia; Ochoa, Carlos; Arnaez, Juan

2018-07-01

High-flow nasal cannula (HFNC) is increasingly used to provide respiratory support in infants with bronchiolitis. The delivery of aerosol therapy through a jet nebulizer is widely indicated despite its controversial efficacy and poor tolerability. This randomized cross-over study aimed to evaluate the comfort and satisfaction of the delivery of aerosol therapy using a nebulization system integrated into HFNC compared with the standard practice of using a jet nebulizer with a face mask. The COMFORT-Behavior (COMFORT-B) scale, a visual analog scale, and a numeric rating scale were used by health professionals and caregivers to assess subjects' levels of comfort and satisfaction. A total of 113 nebulizations (64 via nebulizer with HFNC; 49 via jet nebulizer) were delivered to the 6 subjects included in the study. Use of the nebulizer with HFNC showed increased comfort and satisfaction during nebulization compared to use of the jet nebulizer, as measured by the COMFORT-B scale, the visual analog scale, and the numeric rating scale, with the following median (interquartile range) scores: 10.7 (7-16) versus 14.5 (10-20) ( P = .006), 8.5 (6-10) versus 7 (4-9) ( P = .02), and 3.84 (3.61-4.07) versus 1.83 (1.58-2.08) ( P < .001), respectively. Correlation between the COMFORT-B scale and the visual analog scale using Spearman's rho was -0.757 ( P < .001). The intraclass correlation coefficient for the COMFORT-B scale, visual analog scale, and numeric rating scale, as measured by 2 different nurses, was between 0.75 and 0.87. The use of a nebulizer incorporated into HFNC therapy results in an increased level of comfort and satisfaction compared to the use of a conventional jet nebulizer in subjects with bronchiolitis who required HFNC therapy. Further studies are needed to determine whether aerosol therapy delivered through HFNC improves the clinical course of this pathology. Copyright © 2018 by Daedalus Enterprises.

Distinguishing rhinitis and nasal neoplasia by radiography.

PubMed

Russo, M; Lamb, C R; Jakovljevic, S

2000-01-01

To compare the incidence of radiographic signs in dogs with rhinitis and primary nasal neoplasia and to assess the performance of observers for distinguishing these conditions, the nasal radiographs of 72 dogs with either rhinitis (n = 42) or primary nasal neoplasia (n = 30) were examined by two independent observers using custom-designed forms to record their interpretations. Rhinitis was associated with a higher incidence of focal or multifocal lesions, localised soft tissue opacities, lucent foci, and a lack of frontal sinus involvement. Neoplasia was associated with soft tissue opacities and loss of turbinate detail that affected the entire ipsilateral nasal cavity, signs of invasion of the bones surrounding the nasal cavity, and soft tissue/fluid opacities within the ipsilateral frontal sinus. The signs with the highest positive predictive value (PPV) for rhinitis were absence of frontal sinus lesions and lucent foci in nasal cavity (PPV of each 82%), and invasion of surrounding bones for neoplasia (PPV 88%). There were no significant differences in the position of the lesion within the nasal cavity, incidence of unilateral versus bilateral lesions, calcified lesions, or absence of teeth. There was moderate agreement between observers about the diagnosis (kappa 0.59). Areas (SE) under ROC curves were 0.94 (0.03) and 0.96 (0.03) for observers A and B, respectively (not significantly different; P = 0.68). These results indicate a high accuracy for radiologists examining dogs with nasal diseases. Differentiation of rhinitis and nasal neoplasia should be based on finding combinations of radiologic signs that together have a high PPV. Differences in interpretation between experienced observers in this study suggest that certain signs are potential sources of error.

Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

PubMed

Mahlumba, Pakama; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

2016-07-30

Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects.

Technological Delivery Systems.

ERIC Educational Resources Information Center

Kennedy, Don; And Others

A section on technological delivery systems, presented as part of the second Australian National Workshop on Distance Education (Perth, 1983), contains four papers on using technological resources to provide educational services to persons in isolated locations. The first paper, by Don Kennedy, covers the use of satellite broadcasting of course…

Delivery System, 2003-2004.

ERIC Educational Resources Information Center

Office of Federal Student Aid (ED), Washington, DC.

This workshop guide for financial aid administrators provides training in the federal student financial aid delivery system. An introduction enables the participant to share some information about his or her responsibilities and to reflect on the relevance of the training to the job. Session 1, "Application Systems," identifies methods of applying…

Drug Delivery and Nanoformulations for the Cardiovascular System.

PubMed

Geldenhuys, W J; Khayat, M T; Yun, J; Nayeem, M A

2017-02-01

Therapeutic delivery to the cardiovascular system may play an important role in the successful treatment of a variety of disease state, including atherosclerosis, ischemic-reperfusion injury and other types of microvascular diseases including hypertension. In this review we evaluate the different options available for the development of suitable delivery systems that include the delivery of small organic compounds [adenosin A 2A receptor agonist (CGS 21680), CYP-epoxygenases inhibitor (N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide, trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy] benzoic acid), soluble epoxide hydrolase inhibitor (N-methylsulfonyl-12,12-dibromododec-11-enamide), PPARγ agonist (rosiglitazone) and PPARγ antagonist (T0070907)], nanoparticles, peptides, and siRNA to the cardiovascular system. Effective formulations of nanoproducts have significant potential to overcome physiological barriers and improve therapeutic outcomes in patients. As per the literature covering targeted delivery to the cardiovascular system, we found that this area is still at infancy stage, as compare to the more mature fields of tumor cancer or brain delivery (e.g. blood-brain barrier permeability) with fewer publications focused on the targeted drug delivery technologies. Additionally, we show how pharmacology needs to be well understood when considering the cardiovascular system. Therefore, we discussed in this review various receptors agonists, antagonists, activators and inhibitors which will have effects on cardiovascular system.

[Usage of polyvinylpyrrolidonic films for nasal cavity tamponade].

PubMed

Kriukov, A I; Karel'skaia, N A; Kleshnin, D A; Pashkin, I I

2006-01-01

The experience in otorhinolaryngological application of hydrogel films for nasal tamponade in nasal hemorrhage after surgical interventions on the intranasal structures and in nasal hemorrhage in leukemia patients was analysed.

Evidence-based management of nasal polyposis by intranasal corticosteroids: from the cause to the clinic.

PubMed

Bachert, Claus

2011-01-01

Nasal polyposis is an inflammatory disorder involving the mucosa of the nose and paranasal sinuses and affecting approximately 2-4% of the general population. A literature search of Medline and Embase was conducted to obtain an overview of the epidemiology, pathophysiology, and current treatment of nasal polyposis, focusing on evidence-based efficacy of intranasal corticosteroids (INSs) as primary and postoperative therapy. Recent research on INSs in nasal polyp treatment, along with notable historic findings, was reviewed. Nasal polyps are mostly characterized by eosinophil infiltration, a complex inflammation of nasal mucosa, and possibly production of polyclonal IgE. Current treatment modalities include INSs, oral corticosteroids, and surgery; surgery is generally limited to those with an insufficient response to medical treatment. Because of their effects on eosinophil-dominated inflammation, INSs and oral corticosteroids are the primary medical treatment strategies. The very low (≤1%) systemic bioavailability of newer INSs minimizes the systemic adverse effects seen with oral corticosteroids. Based on randomized, controlled trials, guidelines recommend INSs as first-line therapy for nasal polyps and for care after polypectomy. Clinical data suggest INSs are effective in reducing polyp size and relieving nasal symptoms. INS treatment has also reduced nasal polyp recurrence in patients undergoing functional endoscopic sinus surgery. Treatment with these mainstay options has been found to improve quality of life, which, along with symptom improvement, is a key factor in disease treatment. Copyright © 2011 S. Karger AG, Basel.

21 CFR 868.5350 - Nasal oxygen catheter.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nasal oxygen catheter. 868.5350 Section 868.5350...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5350 Nasal oxygen catheter. (a) Identification. A nasal oxygen catheter is a device intended to be inserted through a patient's nostril to...

21 CFR 868.5340 - Nasal oxygen cannula.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasal oxygen cannula. 868.5340 Section 868.5340...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5340 Nasal oxygen cannula. (a) Identification. A nasal oxygen cannula is a two-pronged device used to administer oxygen to a patient through...

21 CFR 868.5340 - Nasal oxygen cannula.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasal oxygen cannula. 868.5340 Section 868.5340...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5340 Nasal oxygen cannula. (a) Identification. A nasal oxygen cannula is a two-pronged device used to administer oxygen to a patient through...

21 CFR 868.5350 - Nasal oxygen catheter.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasal oxygen catheter. 868.5350 Section 868.5350...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5350 Nasal oxygen catheter. (a) Identification. A nasal oxygen catheter is a device intended to be inserted through a patient's nostril to...

21 CFR 868.5340 - Nasal oxygen cannula.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nasal oxygen cannula. 868.5340 Section 868.5340...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5340 Nasal oxygen cannula. (a) Identification. A nasal oxygen cannula is a two-pronged device used to administer oxygen to a patient through...

21 CFR 868.5340 - Nasal oxygen cannula.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasal oxygen cannula. 868.5340 Section 868.5340...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5340 Nasal oxygen cannula. (a) Identification. A nasal oxygen cannula is a two-pronged device used to administer oxygen to a patient through...

21 CFR 868.5340 - Nasal oxygen cannula.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasal oxygen cannula. 868.5340 Section 868.5340...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5340 Nasal oxygen cannula. (a) Identification. A nasal oxygen cannula is a two-pronged device used to administer oxygen to a patient through...

21 CFR 868.5350 - Nasal oxygen catheter.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasal oxygen catheter. 868.5350 Section 868.5350...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5350 Nasal oxygen catheter. (a) Identification. A nasal oxygen catheter is a device intended to be inserted through a patient's nostril to...

21 CFR 868.5350 - Nasal oxygen catheter.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasal oxygen catheter. 868.5350 Section 868.5350...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5350 Nasal oxygen catheter. (a) Identification. A nasal oxygen catheter is a device intended to be inserted through a patient's nostril to...

21 CFR 868.5350 - Nasal oxygen catheter.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasal oxygen catheter. 868.5350 Section 868.5350...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5350 Nasal oxygen catheter. (a) Identification. A nasal oxygen catheter is a device intended to be inserted through a patient's nostril to...

Light-switchable systems for remotely controlled drug delivery.

PubMed

Shim, Gayong; Ko, Seungbeom; Kim, Dongyoon; Le, Quoc-Viet; Park, Gyu Thae; Lee, Jaiwoo; Kwon, Taekhyun; Choi, Han-Gon; Kim, Young Bong; Oh, Yu-Kyoung

2017-12-10

Light-switchable systems have recently received attention as a new mode of remotely controlled drug delivery. In the past, a multitude of nanomedicine studies have sought to enhance the specificity of drug delivery to target sites by focusing on receptors overexpressed on malignant cells or environmental features of diseases sites. Despite these immense efforts, however, there are few clinically available nanomedicines. We need a paradigm shift in drug delivery. One strategy that may overcome the limitations of pathophysiology-based drug delivery is the use of remotely controlled delivery technology. Unlike pathophysiology-based active drug targeting strategies, light-switchable systems are not affected by the heterogeneity of cells, tissue types, and/or microenvironments. Instead, they are triggered by remote light (i.e., near-infrared) stimuli, which are absorbed by photoresponsive molecules or three-dimensional nanostructures. The sequential conversion of light to heat or reactive oxygen species can activate drug release and allow it to be spatio-temporally controlled. Light-switchable systems have been used to activate endosomal drug escape, modulate the release of chemical and biological drugs, and alter nanoparticle structures to control the release rates of drugs. This review will address the limitations of pathophysiology-based drug delivery systems, the current status of light-based remote-switch systems, and future directions in the application of light-switchable systems for remotely controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Normal and variant anatomy of the nasal tip.

PubMed

Ketcham, Amy S; Dobratz, Eric J

2012-04-01

A thorough understanding of nasal tip anatomy is a prerequisite to understanding the nuances of restructuring the nasal tip. The three-dimensional structural anatomy of the nasal tip is complex. Additionally, the interrelationship between these structures determines the ultimate form and function of the nasal tip. As a result, alteration of one structure in the tip will often lead to change in other portions of the nasal tip. This dynamic concept of anatomy in the nasal tip makes proper alteration of the nasal tip one of the most challenging tasks faced by a rhinoplasty surgeon. This article provides a fundamental knowledge of the normal anatomy of the tip structures and how their interaction with each other determines the shape and support of the lower portion of the nose. It also provides a description of some common variants of tip anatomy that cause patients to seek consultation for rhinoplasty. A proper understanding of the concepts presented provides a foundation to build on as the reader continues to explore the "nuances of the nasal tip." Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Allergic rhinitis-induced nasal congestion: its impact on sleep quality.

PubMed

Storms, William

2008-03-01

Allergic rhinitis (AR) is an extremely common health problem affecting 20 to 40 million Americans and between 10-25% of the world's population. Patients with AR suffer from both nasal symptoms (congestion, rhinorrhea, itching, and sneezing) and ocular symptoms (itching, redness, and tearing). The negative impact on sleep quality and quantity, and consequently on various aspects of the patient's life, is an under-recognised and under-treated component of AR morbidity. Nasal congestion, which is one of the most bothersome and prevalent symptoms of AR, is thought to be the leading symptom responsible for rhinitis-related sleep problems. In addition to reducing clinical symptoms, pharmacologic therapies for AR that specifically reduce inflammatory cells and mediators - and therefore nasal congestion and other symptoms - should also improve sleep quality and overall quality of life (QOL). Intranasal corticosteroids (INS) are the current mainstay of therapy for AR. Results of a number of clinical trials demonstrate that INS effectively reduce nasal congestion and ocular symptoms, improve sleep quality, and decrease daytime somnolence. Intranasal corticosteroids have also proved to be effective in reducing symptoms of acute rhinosinusitis and nasal polyposis, both of which also negatively impact on sleep quality. Intranasal corticosteroids are considered safe due to their low systemic bioavailability.

Tip rhinoplasty--a modified delivery approach.

PubMed

Xavier, Rui

2009-06-01

For many cases of tip surgery a delivery approach is selected. If the patient has long alar cartilages, it may be difficult to deliver the cartilages without twisting or tearing the domes. In such a patient, a modified delivery approach may be easier to perform. For the modified delivery approach a transcartilaginous incision is first made and cephalic resection of the alar cartilage is performed. Then a marginal incision is made, and the remaining alar cartilage is dissected and easily delivered. After both alar cartilages being delivered, they are compared, and, if necessary, further resection is done in order to achieve perfect symmetry or to achieve the desired size of the cartilages. The cartilages may then be grafted, sutured or modified as considered necessary. We have been using the modified delivery approach for the last five years and we have had no complications of the technique itself. Two patients operated on by using this approach are presented. We believe that, in patients with long alar cartilages and a wide nasal tip, this modification turns the delivery approach into an easier and safer approach.

Normative Nasalance Scores for Brazilian Portuguese Using New Speech Stimuli.

PubMed

Marino, Viviane Cristina de Castro; Dutka, Jeniffer de Cássia Rillo; de Boer, Gillian; Cardoso, Vanessa Moraes; Ramos, Renata Giorgetto; Bressmann, Tim

2015-01-01

Normative data were established for newly developed speech materials for nasalance assessment in Brazilian Portuguese. Nasalance scores of preexisting passages (oral ZOO-BR, low-pressure oral ZOO-BR2 and NASAL-BR), new nasalance passages (oral Dudu no zoológico, oral Dudu no bosque, oral-nasal O cãozinho Totó and nasal O nenê) and Brasilcleft articulation screening sentences were collected from 245 speakers of Brazilian Portuguese, including 121 males and 124 females, divided into 4 groups: children (5-9 years), adolescents (10-19 years), young adults (20-24 years) and adults (25-35 years). Across all nasalance passages, adult females scored on average 2 percentage points higher than males. Children scored 2-4 percentage points lower than older groups for the preexisting nasalance passages ZOO-BR and ZOO-BR2. Nasalance scores for the new nasalance passages were not significantly different from the preexisting passages. Scores for high-pressure sentences did not differ significantly from the oral nasalance passage Dudu no bosque. The nasalance scores for the new nasalance passages were equivalent to the preexisting materials. The new shortened and simplified nasalance passages will be useful for assessing young children. Normative scores for the Brasilcleft high-pressure sentences were equivalent to the new oral passage Dudu no bosque. © 2016 S. Karger AG, Basel.

Elastin-Like Recombinamers As Smart Drug Delivery Systems.

PubMed

Arias, F Javier; Santos, Mercedes; Ibanez-Fonseca, Arturo; Pina, Maria Jesus; Serrano, Sofía

2018-02-19

Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self-assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A prospective 8 week trial of nasal interfaces vs. a novel oral interface (Oracle) for treatment of obstructive sleep apnea hypopnea syndrome.

PubMed

Khanna, Ritu; Kline, Lewis R

2003-07-01

To compare efficacy, compliance rates, and side effects of a new strapless oral interface, the Oracle, with available nasal masks over 8 weeks of use for the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 38 patients with OSAHS (respiratory disturbance index (RDI) >/=15/h) were enrolled after the diagnostic polysomnogram for subsequent continuous positive airway pressure (CPAP) therapy. After randomization, therapeutic pressures during a titration study were determined for 21 patients in the oral group and 17 patients in the nasal group. Comparisons for nasal and oral interfaces were made for baseline patient characteristics, average hours of CPAP use, side effects from therapy, and among questionnaires evaluating patients' subjective responses to therapy at months 1 and 2. No significant difference was observed in the average hours of CPAP use between the oral (4.5+/-2.1; 5.5+/-2.6) and nasal groups (4.0+/-2.6; 4.8+/-2.5) for either month 1 or 2 (P>0.05). The dropout rates were similar for both groups after 8 weeks of therapy. However, patients in the nasal group had higher occurrences of side effects such as nasal congestion, dryness, and air leaks, whereas patients in the oral group experienced more oral dryness and gum pain. Oral delivery of CPAP with the Oracle is an effective and suitable alternative for patients with OSAHS.

Nasal patency and otorhinolaryngologic-orofacial features in children.

PubMed

Milanesi, Jovana de Moura; Berwig, Luana Cristina; Schuch, Luiz Henrique; Ritzel, Rodrigo Agne; Silva, Ana Maria Toniolo da; Corrêa, Eliane Castilhos Rodrigues

2017-11-21

Nasal obstruction is a common symptom in childhood, related to rhinitis and pharyngeal tonsil hypertrophy. In the presence of nasal obstruction, nasal patency may be reduced, and nasal breathing is replaced by mouth breathing. Orofacial and otorhinolaryngologic changes are related to this breathing mode. Objective evaluation of upper airways may be obtained through nasal patency measurement. To compare nasal patency and otorhinolaryngologic-orofacial features in children. One hundred and twenty three children, 6-12 year-old, and of both sexes underwent speech therapy evaluation, according to Orofacial Myofunctional Evaluation protocol, clinical and endoscopic otorhinolaryngologic examination and nasal patency measurement, using the absolute and predicted (%) peak nasal inspiratory flow values. Lower values of absolute and estimated peak nasal inspiratory flow values were found in children with restless sleep (p=0.006 and p=0.002), nasal obstruction report (p=0.027 and p=0.023), runny nose (p=0.004 and p=0.012), unsystematic lip closure during mastication (p=0.040 and p=0.026), masticatory speed reduced (p=0.006 and p=0.008) and altered solid food swallowing (p=0.006 and p=0.001). Absolute peak nasal inspiratory flow was lower in children with pale inferior turbinate (p=0.040), reduced hard palate width (p=0.037) and altered speech (p=0.004). Higher absolute values were found in children with increased tongue width (p=0.027) and, higher absolute and predicted (%) in children with mild everted lip (p=0.008 and p=0.000). Nasal patency was lower in children with restless sleep, rhinitis signs and symptoms, hard palate width reduced and with changes in mastication, deglutition and speech functions. It is also emphasized that most of the children presented signs and symptom of allergic rhinitis. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Impact of Absorption and Transport on Intelligent Therapeutics and Nano-scale Delivery of Protein Therapeutic Agents

PubMed Central

Peppas, Nicholas A.; Carr, Daniel A

2009-01-01

The combination of materials design and advances in nanotechnology has led to the development of new therapeutic protein delivery systems. The pulmonary, nasal, buccal and other routes have been investigated as delivery options for protein therapy, but none result in improved patient compliances and patient quality of life as the oral route. For the oral administration of these new systems, an understanding of protein transport is essential because of the dynamic nature of the gastrointestinal tract and the barriers to transport that exist. Models have been developed to describe the transport between the gastrointestinal lumen and the bloodstream, and laboratory techniques like cell culture provide a means to investigate the absorption and transport of many therapeutic agents. Biomaterials, including stimuli-sensitive complexation hydrogels, have been investigated as promising carriers for oral delivery. However, the need to develop models that accurately predict protein blood concentration as a function of the material structure and properties still exists. PMID:20161384

Deep Space Systems Technology Program Future Deliveries

NASA Technical Reports Server (NTRS)

Salvo, Christopher G.; Keuneke, Matthew S.

2000-01-01

NASA is in a period of frequent launches of low cost deep space missions with challenging performance needs. The modest budgets of these missions make it impossible for each to develop its own technology, therefore, efficient and effective development and insertion of technology for these missions must be approached at a higher level than has been done in the past. The Deep Space Systems Technology Program (DSST), often referred to as X2000, has been formed to address this need. The program is divided into a series of "Deliveries" that develop and demonstrate a set of spacecraft system capabilities with broad applicability for use by multiple missions. The First Delivery Project, to be completed in 2001, will provide a one MRAD-tolerant flight computer, power switching electronics, efficient radioisotope power source, and a transponder with services at 8.4 GHz and 32 GHz bands. Plans call for a Second Delivery in late 2003 to enable complete deep space systems in the 10 to 50 kg class, and a Third Delivery built around Systems on a Chip (extreme levels of electronic and microsystems integration) around 2006. Formulation of Future Deliveries (past the First Delivery) is ongoing and includes plans for such developments as highly miniaturized digital/analog/power electronics, optical communications, multifunctional structures, miniature lightweight propulsion, advanced thermal control techniques, highly efficient radioisotope power sources, and a unified flight ground software architecture to support the needs of future highly intelligent space systems. All developments are targeted at broad applicability and reuse, and will be commercialized within the US.

Acoustic Analysis of Nasal Vowels in Monguor Language

NASA Astrophysics Data System (ADS)

Zhang, Hanbin

2017-09-01

The purpose of the study is to analyze the spectrum characteristics and acoustic features for the nasal vowels [ɑ˜] and [ɔ˜] in Monguor language. On the base of acoustic parameter database of the Monguor speech, the study finds out that there are five main zero-pole pairs appearing for the nasal vowel [ɔ˜] and two zero-pole pairs appear for the nasal vowel [ɔ˜]. The results of regression analysis demonstrate that the duration of the nasal vowel [ɔ˜] or the nasal vowel [ɔ˜] can be predicted by its F1, F2 and F3 respectively.

Microneedles As a Delivery System for Gene Therapy

PubMed Central

Chen, Wei; Li, Hui; Shi, De; Liu, Zhenguo; Yuan, Weien

2016-01-01

Gene delivery systems can be divided to two major types: vector-based (either viral vector or non-viral vector) and physical delivery technologies. Many physical carriers, such as electroporation, gene gun, ultrasound start to be proved to have the potential to enable gene therapy. A relatively new physical delivery technology for gene delivery consists of microneedles (MNs), which has been studied in many fields and for many molecule types and indications. Microneedles can penetrate the stratum corneum, which is the main barrier for drug delivery through the skin with ease of administration and without significant pain. Many different kinds of MNs, such as metal MNs, coated MNs, dissolving MNs have turned out to be promising in gene delivery. In this review, we discussed the potential as well as the challenges of utilizing MNs to deliver nucleic acids for gene therapy. We also proposed that a combination of MNs and other gene delivery approaches may lead to a better delivery system for gene therapy. PMID:27303298

Oronasal Masks Require a Higher Pressure than Nasal and Nasal Pillow Masks for the Treatment of Obstructive Sleep Apnea.

PubMed

Deshpande, Sheetal; Joosten, Simon; Turton, Anthony; Edwards, Bradley A; Landry, Shane; Mansfield, Darren R; Hamilton, Garun S

2016-09-15

Oronasal masks are frequently used for continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). The aim of this study was to (1) determine if CPAP requirements are higher for oronasal masks compared to nasal mask interfaces and (2) assess whether polysomnography and patient characteristics differed among mask preference groups. Retrospective analysis of all CPAP implementation polysomnograms between July 2013 and June 2014. Prescribed CPAP level, polysomnography results and patient data were compared according to mask type (n = 358). Oronasal masks were used in 46%, nasal masks in 35% and nasal pillow masks in 19%. There was no difference according to mask type for baseline apnea-hypopnea index (AHI), body mass index (BMI), waist or neck circumference. CPAP level was higher for oronasal masks, 12 (10-15.5) cm H2O compared to nasal pillow masks, 11 (8-12.5) cm H2O and nasal masks, 10 (8-12) cm H2O, p < 0.0001 (Median [interquartile range]). Oronasal mask type, AHI, age, and BMI were independent predictors of a higher CPAP pressure (p < 0.0005, adjusted R(2) = 0.26.). For patients with CPAP ≥ 15 cm H2O, there was an odds ratio of 4.5 (95% CI 2.5-8.0) for having an oronasal compared to a nasal or nasal pillow mask. Residual median AHI was higher for oronasal masks (11.3 events/h) than for nasal masks (6.4 events/h) and nasal pillows (6.7 events/h), p < 0.001. Compared to nasal mask types, oronasal masks are associated with higher CPAP pressures (particularly pressures ≥ 15 cm H2O) and a higher residual AHI. Further evaluation with a randomized control trial is required to definitively establish the effect of mask type on pressure requirements. A commentary on this article appears in this issue on page 1209. © 2016 American Academy of Sleep Medicine.

Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles

PubMed Central

Pan, Li; Zhang, Zhongwang; Lv, Jianliang; Zhou, Peng; Hu, Wenfa; Fang, Yuzhen; Chen, Haotai; Liu, Xinsheng; Shao, Junjun; Zhao, Furong; Ding, Yaozhong; Lin, Tong; Chang, Huiyun; Zhang, Jie; Zhang, Yongguang; Wang, Yonglu

2014-01-01

The aim of this study was to enhance specific mucosal, systemic, and cell-mediated immunity and to induce earlier onset of protection against direct-contact challenge in cattle by intranasal delivery of a nanoparticle-based nasal vaccine against type A foot-and-mouth disease (FMD). In this study, two kinds of nanoparticle-based nasal vaccines against type A FMD were designed: (1) chitosan-coated poly(lactic-co-glycolic acid) (PLGA) loaded with plasmid DNA (Chi-PLGA-DNA) and (2) chitosan-trehalose and inactivated foot-and-mouth disease virus (FMDV) (Chi-Tre-Inactivated). Cattle were immunized by an intranasal route with nanoparticles and then challenged for 48 hours by direct contact with two infected donor cattle per pen. Donors were inoculated intradermally in the tongue 48 hours before challenge, with 0.2 mL cattle-passaged FMDV. Serological and mucosal antibody responses were evaluated, and virus excretion and the number of contact infections were quantified. FMDV-specific secretory immunoglobulin (Ig)A (sIgA) antibodies in nasal washes were initially detected at 4 days postvaccination (dpv) with two kinds of nanoparticles. The highest levels of sIgA expression were observed in nasal washes, at 10 dpv, from animals with Chi-PLGA-DNA nanoparticles, followed by animals immunized once by intranasal route with a double dose of Chi-Tre-Inactivated nanoparticles and animals immunized by intranasal route three times with Chi-Tre-Inactivated nanoparticles (P<0.05). FMDV-specific IgA antibodies in serum showed a similar pattern. All animals immunized by intranasal route developed low levels of detectable IgG in serum at 10 dpv. Following stimulation with FMDV, the highest levels of proliferation were observed in splenocytes harvested from Chi-PLGA-DNA-immunized animals, followed by proliferation of cells harvested from Chi-Tre-Inactivated nanoparticle-immunized animals (P<0.05). Higher protection rates were associated with the highest sIgA antibody responses induced in

Alkaline phosphatase in nasal secretion of cattle: biochemical and molecular characterisation.

PubMed

Ghazali, M Faizal; Koh-Tan, H H Caline; McLaughlin, Mark; Montague, Paul; Jonsson, Nicholas N; Eckersall, P David

2014-09-05

Nasal secretion (NS) was investigated as a source of information regarding the mucosal and systemic immune status of cattle challenged by respiratory disease. A method for the collection of substantial volumes (~12 ml) of NS from cattle was developed to establish a reference range of analytes that are present in the NS of healthy cattle. Biochemical profiles of NS from a group of 38 healthy Holstein-Friesian cows revealed high alkaline phosphatase (AP) activity of up to 2392 IU/L. The character and source of the high activity of AP in bovine NS was investigated. Histochemical analysis confirmed the localization of the AP enzyme activity to epithelial cells and serous glands of the nasal respiratory mucosa. Analysis of mRNA levels from nasal mucosa by end point RT-PCR and PCR product sequencing confirmed that the AP was locally produced and is identical at the nucleotide level to the non-specific AP splice variant found in bovine liver, bone and kidney. Analysis by isoelectric focussing confirmed that AP was produced locally at a high level in nasal epithelium demonstrating that AP from nasal secretion and nasal mucosa had similar pI bands, though differing from those of the liver, kidney, bone and intestine, suggesting different post-translational modification (PTM) of AP in these tissues. A nasal isozyme of AP has been identified that is present at a high activity in NS, resulting from local production and showing distinctive PTM and may be active in NS as an anti-endotoxin mediator.

Finasteride topical delivery systems for androgenetic alopecia.

PubMed

Khan, Muhammad Zia Ullah; Khan, Shujaat Ali; Ubaid, Muhammad; Shah, Aamna; Kousar, Rozina; Murtaza, Ghulam

2018-01-23

Androgenetic alopecia, generally recognized as male pattern baldness, is a gradually developing medical and physiological change, which is manifested by continuous hair-loss from scalp. Finasteride (4-aza-3-oxosteroid) is a potent anti-baldness compound that selectively and competitively inhibits the 5α-reductase isoenzymes. Prolonged oral use of finasteride leads to the emergence of sexual disorders including decrease in libido, gynecomastia, erectile dysfunction, ejaculation disorder, orgasm disorders and mood disturbances. Since, hair follicles widely home in 5α-reductase, topical formulations of finasteride in comparison to its oral formulations are expected to potentially reduce its systemic adverse effects. The analysis of literature has revealed some delivery systems developed for the enhanced and localized penetration of finasteride into the skin. These finasteride delivery systems include polymersomes, vesicular nanocarriers, vesicular ethosomal carriers, liposomes and niosomes, liquid crystalline nanoparticles, topical solutions and gels. The aim of this review article is to briefly amass all literature on topical delivery of finasteride to elaborate best dosage form, i.e. formulation having maximum permeation rate. This study will serve as a future perspective regarding topical delivery of finasteride. The literature analysis has exhibited that most of the previous investigators have used propylene glycol in their finasteride-loaded topical formulations, while poloxamer P407, monoolein, transcutol P and choline was used in few formulations. Moreover among all drug delivery systems, finasteride liposomal gel system consisting of 2% methyl cellulose and gel system containing poloxamer P407 exhibited the highest flux with a value of 28.4 ± 1.3 µg/cm2h and 23.1 ± 1.4 µg/cm2h, respectively. Several topical drug delivery techniques such as topical microneedles, aerosol foams, nanoemulsions, microsponges, and emulsifier free formulations, fullerenes

Superparamagnetic Iron Oxide Nanoparticle-Based Delivery Systems for Biotherapeutics

PubMed Central

Mok, Hyejung; Zhang, Miqin

2014-01-01

Introduction Superparamagnetic iron oxide nanoparticle (SPION)-based carrier systems have many advantages over other nanoparticle-based systems. They are biocompatible, biodegradable, facilely tunable, and superparamagnetic and thus controllable by an external magnetic field. These attributes enable their broad biomedical applications. In particular, magnetically-driven carriers are drawing considerable interest as an emerging therapeutic delivery system because of their superior delivery efficiency. Area covered This article reviews the recent advances in use of SPION-based carrier systems to improve the delivery efficiency and target specificity of biotherapeutics. We examine various formulations of SPION-based delivery systems, including SPION micelles, clusters, hydrogels, liposomes, and micro/nanospheres, as well as their specific applications in delivery of biotherapeutics. Expert opinion Recently, biotherapeutics including therapeutic cells, proteins and genes have been studied as alternative treatments to various diseases. Despite the advantages of high target specificity and low adverse effects, clinical translation of biotherapeutics has been hindered by the poor stability and low delivery efficiency compared to chemical drugs. Accordingly, biotherapeutic delivery systems that can overcome these limitations are actively pursued. SPION-based materials can be ideal candidates for developing such delivery systems because of their excellent biocompatibility and superparamagnetism that enables long-term accumulation/retention at target sites by utilization of a suitable magnet. In addition, synthesis technologies for production of finely-tuned, homogeneous SPIONs have been well developed, which may promise their rapid clinical translation. PMID:23199200

Optical diagnostics integrated with laser spark delivery system

DOEpatents

Yalin, Azer [Fort Collins, CO; Willson, Bryan [Fort Collins, CO; Defoort, Morgan [Fort Collins, CO; Joshi, Sachin [Fort Collins, CO; Reynolds, Adam [Fort Collins, CO

2008-09-02

A spark delivery system for generating a spark using a laser beam is provided, and includes a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. The laser delivery assembly further includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. Other embodiments use a fiber laser to generate a spark. Embodiments of the present invention may be used to create a spark in an engine. Yet other embodiments include collecting light from the spark or a flame resulting from the spark and conveying the light for diagnostics. Methods of using the spark delivery systems and diagnostic systems are provided.

Controlled drug delivery systems: past forward and future back.

PubMed

Park, Kinam

2014-09-28

Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology. Copyright © 2014 Elsevier B.V. All rights reserved.

Convection-enhanced delivery to the central nervous system.

PubMed

Lonser, Russell R; Sarntinoranont, Malisa; Morrison, Paul F; Oldfield, Edward H

2015-03-01

Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

Diagnostic strategies in nasal congestion

PubMed Central

Krouse, John; Lund, Valerie; Fokkens, Wytske; Meltzer, Eli O

2010-01-01

Nasal congestion is a major symptom of upper respiratory tract disorders, and its characterization an important part of the diagnosis of these illnesses. Patient history and assessment of nasal symptoms are essential components of diagnosis, providing an initial evaluation that may be adequate to rule out serious conditions. However, current congestion medications are not always fully effective. Thus, if symptoms do not respond adequately to therapy, or symptoms suggestive of more serious conditions are present, specialized assessments may be needed. Various techniques are available for diagnosing patients, including those used chiefly by primary care clinicians and those requiring the expertise of otolaryngologists, allergists, and other specialists. Endoscopy remains a mainstay for evaluating nasal blockage and its causes, while modalities such as peak nasal inspiratory flow and acoustic rhinometry are evolving to provide easy-to-use, noninvasive procedures that are sensitive enough to measure small but clinically important abnormalities and therapeutic changes. Several imaging modalities are available to the specialist for severe or unusual cases, as are specialized diagnostic procedures that measure adjunctive features of congestion, such as impaired mucociliary function. PMID:20463824

Rivastigmine-loaded in situ gelling nanostructured lipid carriers for nose to brain delivery.

PubMed

Wavikar, Preeti R; Vavia, Pradeep R

2015-01-01

In the current research work, rivastigmine (RV)-loaded in situ gelling nanostructured lipid carriers (NLCs) were developed for nose to brain delivery. NLCs were fabricated by ethanol injection method using glyceryl monosterate, Capmul MCM C8, Lecithin and Tween 80. NLCs showed average particle size of 123.2 ± 2.3 nm with entrapment efficiency of 68.34 ± 3.4%. DSC, XRD and IR studies showed complete amorphization and incorporation of the drug into nanoparticles. NLCs were incorporated into an in situ gelling system using 0.8% gellan gum and 15% Lutrol F 127. RV in situ gel showed excellent elasticity, rheology, mucoadhesion and adhesiveness to facilitate its adhesion to the upper nasal mucosa. NLC-based in situ gel showed a 2-fold increase in nasal permeation of the drug over plain RV solution. In situ gelling NLCs showed a 3-fold increase in enzyme inhibition efficacy.

Enterprise networks. Strategies for integrated delivery systems.

PubMed

Siwicki, B

1997-02-01

More integrated delivery systems are making progress toward building computer networks that link all their care delivery sites so they can efficiently and economically coordinate care. A growing number of these systems are turning to intranets--private computer networks that use Internet-derived protocols and technologies--to move information that's essential to managing scare health care resources.

Development of the Choctaw Health Delivery System.

ERIC Educational Resources Information Center

Nguyen, Binh N.

The Choctaw Tribe is the first and only tribe to develop a health delivery system to take over an existing Indian Health Service inpatient facility. The takeover was accomplished in January 1984 under the Indian Self-Determination Act through a contract with the Indian Health Service. The Choctaw Health Delivery System includes a 35-bed general…

Drug self-delivery systems for cancer therapy.

PubMed

Qin, Si-Yong; Zhang, Ai-Qing; Cheng, Si-Xue; Rong, Lei; Zhang, Xian-Zheng

2017-01-01

Carrier-assistant drug delivery systems (DDSs) have been rapidly established for cancer therapy and great strides have been made in recent years. However, further development of DDSs is retarded by the aspects such as the low drug carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. Drug self-delivery systems (DSDSs), in which active drugs exhibit nanoscale characteristic to realize intracellular delivery by themselves without the help of nanocarriers, have been rapidly developed to address these issues. In this review, we present a comprehensive summary of the recent advances in DSDSs for cancer therapy. After a brief introduction to the major types of DSDSs and their fabrication strategies, we emphatically discuss some representative achievements of these DSDSs for passive or/and positive targeting therapy, combinational therapy as well as theranostics. The design principle is explained and justified, which can cast a new light on developing drug delivery systems for cancer treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Finite Element Model and Validation of Nasal Tip Deformation

PubMed Central

Manuel, Cyrus T; Harb, Rani; Badran, Alan; Ho, David; Wong, Brian JF

2016-01-01

Nasal tip mechanical stability is important for functional and cosmetic nasal airway surgery. Palpation of the nasal tip provides information on tip strength to the surgeon, though it is a purely subjective assessment. Providing a means to simulate nasal tip deformation with a validated model can offer a more objective approach in understanding the mechanics and nuances of the nasal tip support and eventual nasal mechanics as a whole. Herein we present validation of a finite element (FE) model of the nose using physical measurements recorded using an ABS plastic-silicone nasal phantom. Three-dimensional photogrammetry was used to capture the geometry of the phantom at rest and while under steady state load. The silicone used to make the phantom was mechanically tested and characterized using a linear elastic constitutive model. Surface point clouds of the silicone and FE model were compared for both the loaded and unloaded state. The average Hausdorff distance between actual measurements and FE simulations across the nose were 0.39mm ± 1.04 mm and deviated up to 2mm at the outermost boundaries of the model. FE simulation and measurements were in near complete agreement in the immediate vicinity of the nasal tip with millimeter accuracy. We have demonstrated validation of a two-component nasal FE model, which could be used to model more complex modes of deformation where direct measurement may be challenging. This is the first step in developing a nasal model to simulate nasal mechanics and ultimately the interaction between geometry and airflow. PMID:27633018

Finite Element Model and Validation of Nasal Tip Deformation.

PubMed

Manuel, Cyrus T; Harb, Rani; Badran, Alan; Ho, David; Wong, Brian J F

2017-03-01

Nasal tip mechanical stability is important for functional and cosmetic nasal airway surgery. Palpation of the nasal tip provides information on tip strength to the surgeon, though it is a purely subjective assessment. Providing a means to simulate nasal tip deformation with a validated model can offer a more objective approach in understanding the mechanics and nuances of the nasal tip support and eventual nasal mechanics as a whole. Herein we present validation of a finite element (FE) model of the nose using physical measurements recorded using an ABS plastic-silicone nasal phantom. Three-dimensional photogrammetry was used to capture the geometry of the phantom at rest and while under steady state load. The silicone used to make the phantom was mechanically tested and characterized using a linear elastic constitutive model. Surface point clouds of the silicone and FE model were compared for both the loaded and unloaded state. The average Hausdorff distance between actual measurements and FE simulations across the nose were 0.39 ± 1.04 mm and deviated up to 2 mm at the outermost boundaries of the model. FE simulation and measurements were in near complete agreement in the immediate vicinity of the nasal tip with millimeter accuracy. We have demonstrated validation of a two-component nasal FE model, which could be used to model more complex modes of deformation where direct measurement may be challenging. This is the first step in developing a nasal model to simulate nasal mechanics and ultimately the interaction between geometry and airflow.

Nasal Myiasis in Hinduism and Contemporary Otorhinolaryngology.

PubMed

Bosmia, Anand N; Zimmermann, Terence M; Griessenauer, Christoph J; Shane Tubbs, R; Rosenthal, Eben L

2017-08-01

Various case reports on nasal myiasis written during the 1990s and 2000s state that nasal myiasis, which is known as peenash among South Asian natives, is a form of divine punishment in Hindu mythology, but do not provide citations from Hindu scriptures that would suggest this interpretation. This paper aims to discuss the phenomenon of peenash in a historical context by examining medical literature written during the nineteenth and early twentieth centuries, to identify Hindu texts contributing to the belief of some Hindus that nasal myiasis is a form of divine punishment, and to provide an overview of contemporary treatment for and management of nasal myiasis.

Emerging potential of stimulus-responsive nanosized anticancer drug delivery systems for systemic applications.

PubMed

Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Madeshwaran, Thiagarajan; Hiep, Tran Tuan; Kandasamy, Umadevi; Oh, Kyung Taek; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2018-02-01

The development of novel drug delivery systems based on well-defined polymer therapeutics has led to significant improvements in the treatment of multiple disorders. Advances in material chemistry, nanotechnology, and nanomedicine have revolutionized the practices of drug delivery. Stimulus-responsive material-based nanosized drug delivery systems have remarkable properties that allow them to circumvent biological barriers and achieve targeted intracellular drug delivery. Specifically, the development of novel nanocarrier-based therapeutics is the need of the hour in managing complex diseases. In this review, we have briefly described the fundamentals of drug targeting to diseased tissues, physiological barriers in the human body, and the mechanisms/modes of drug-loaded carrier systems. To that end, this review serves as a comprehensive overview of the recent developments in stimulus-responsive drug delivery systems, with focus on their potential applications and impact on the future of drug delivery.

Unilateral nasal pain with migraine features.

PubMed

Alvarez, Mónica; Montojo, Teresa; de la Casa, Beatriz; Vela, Lydia; Pareja, Juan A

2013-09-01

Migraine attacks exclusively felt in the face are very rare, the pain involving the territories supplied by the second and third branches of the trigeminal nerve. Two patients suffering from heminasal pain attacks accompanied with typical migrainous features and responsive to oral or intranasal triptans - but not to intranasal lidocaine or oxymetazoline. In one patient, the attacks could be precipitated upon slight touching on the tip of the nose, in the other attacks were preceded by the nasal sensation typically heralding sneezing. Migraine pain mostly develops within the innervation territory of the first branch of the trigeminal nerve, which includes the nose. Therefore, episodes of unilateral nasal pain with migrainous features could be considered a migraine with unusual topography (nasal migraine). Painful nasal attacks occasionally preceded by stimulation of trigeminal afferents in the nose, could be conceived of as migraine-tic syndrome.

Distance Synchronous Information Systems Course Delivery

ERIC Educational Resources Information Center

Peslak, Alan R.; Lewis, Griffith R.; Aebli, Fred

2014-01-01

Teaching computer information systems via distance education is a challenge for both student and faculty. Much research work has been performed on methods of teaching via distance education. Today we are faced with a variety of options for course delivery. Asynchronous delivery via online or lesson instruction still remains most common. But…

Measurement of nasal patency in anesthetized and conscious dogs.

PubMed

Koss, Michael C; Yu, Yongxin; Hey, John A; McLeod, Robbie L

2002-02-01

Experiments were undertaken to characterize a noninvasive chronic, model of nasal congestion in which nasal patency is measured using acoustic rhinometry. Compound 48/80 was administered intranasally to elicit nasal congestion in five beagle dogs either by syringe (0.5 ml) in thiopental sodium-anesthetized animals or as a mist (0.25 ml) in the same animals in the conscious state. Effects of mast cell degranulation on nasal cavity volume as well as on minimal cross-sectional area (A(min)) and intranasal distance to A(min) (D(min)) were studied. Compound 48/80 caused a dose-related decrease in nasal cavity volume and A(min) together with a variable increase in D(min). Maximal responses were seen at 90-120 min. Compound 48/80 was less effective in producing nasal congestion in conscious animals, which also had significantly larger basal nasal cavity volumes. These results demonstrate the utility of using acoustic rhinometry to measure parameters of nasal patency in dogs and suggest that this model may prove useful in studies of the actions of decongestant drugs.

In Vitro Assessment of Spray Deposition Patterns in a Pediatric (12 Year-Old) Nasal Cavity Model.

PubMed

Sawant, Namita; Donovan, Maureen D

2018-03-26

Nasal sprays available for the treatment of cold and allergy symptoms currently use identical formulations and devices for adults as well as for children. Due to the obvious differences between the nasal airway dimensions of a child and those of an adult, the performance of nasal sprays in children was evaluated. Deposition patterns of nasal sprays administered to children were tested using a nasal cast based on MRI images obtained from a 12 year old child's nasal cavity. Test formulations emitting a range of spray patterns were investigated by actuating the device into the pediatric nasal cast under controlled conditions. The results showed that the nasal sprays impacted in the anterior region of the 12 year old child's nasal cavity, and only limited spray entered the turbinate region - the effect site for most topical drugs and the primary absorptive region for systemically absorbed drugs. Differences in deposition patterns following the administration of nasal sprays to adults and children may lead to differences in efficacy between these populations. Greater anterior deposition in children may result in decreased effectiveness, greater anterior dosage form loss, and the increased potential for patient non-compliance.

Biopolymers as transdermal drug delivery systems in dermatology therapy.

PubMed

Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah

2010-01-01

The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use.

Correction of nasal deformity in infants with unilateral cleft lip and palate using multiple digital techniques.

PubMed

Zheng, Yaqi; Zhang, Dapeng; Qin, Tian; Wu, Guofeng

2016-06-01

Presurgical correction of severe nasal deformities before cheiloplasty is often recommended for infants with cleft lip and palate. This article describes an approach for the computer-aided design and fabrication of a nasal molding stent. A 3-dimensional photogrammetric system was used to obtain the shape information of the nosewing that was then built as the nostril support for the nasal molding stent. The stent was fabricated automatically with a rapid prototyping machine. This technique may be an alternative approach to presurgical nasal molding in the clinic. Moreover, the patient's nasal morphology can be saved as clinical data for future study. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Nano drug delivery systems and gamma radiation sterilization.

PubMed

Sakar, F; Özer, A Y; Erdogan, S; Ekizoglu, M; Kart, D; Özalp, M; Colak, S; Zencir, Y

2017-09-01

In recent years, drug delivery systems such as liposomes and microparticles have been used in clinic for the treatment of different diseases and from a regulatory point of view, a parenterally applied drug and drug delivery systems must be sterile and pyrogen free. Radiation sterilization is a method recognized by pharmacopoeias to achieve sterility criteria of parenterals. It has the ability to kill microorganisms in therapeutic products. The ability of, however, irradiation might also affect the performance of drug delivery systems. One of the most critical points is irradiation dose, because certain undesirable chemical and physical changes may accompany with the irradiation, especially with the traditionally applied dose of 25 kGy. Its ionizing property may cause fragmentation of covalent bond. The care must be paid to the applied dose. In this research, the effects of gamma irradiation on different drug delivery systems such as chitosan microparticles, liposomes, niosomes and sphingosomes were investigated. According to the experimental data, it can be concluded that gamma irradiation can be a suitable sterilization technique for liposome, niosome and sphingosome dispersions. When all irradiated drug carrier systems were taken into consideration, chitosan glutamate microparticles were found as the most radioresistant drug delivery system among the others.

Hygroscopic condenser humidifier as a solution to nasal dryness due to nasal CPAP treatment for obstructive sleep apnea syndrome.

PubMed

Parra, O; Klamburg, J; Xirgu, J; Abad, J; Sala, H; Tomasa, A; Morera, J

1991-04-01

We report an apparent solution to nasal dryness for patients with obstructive sleep apnea syndrome treated with nasal continuous positive airway pressure (CPAP) when a hygroscopic condenser humidifier is introduced into the CPAP circuit. Six patients underwent a 5-h test period of nasal CPAP therapy with a mask containing a hygroscopic humidifier. The water vapor showed a statistically significant increase in both inspired and expired gases. The relative humidity of the inspired gases increased significantly. The levels of O2 and CO2 in the respired gases did not change. When patients were asked about nasal dryness at the end of the test, all of them reported marked improvement.

Acoustic rhinometry in the dog: a novel large animal model for studies of nasal congestion.

PubMed

Koss, Michael C; Yu, Yongxin; Hey, John A; McLeod, Robbie L

2002-01-01

The aim of this project was to develop and pharmacologically characterize an experimental dog model of nasal congestion in which nasal patency is measured using acoustic rhinometry. Solubilized compound 48/80 (0.3-3.0%) was administered intranasally to thiopental anesthetized beagle dogs to elicit nasal congestion via localized mast cell degranulation. Compound 48/80-induced effects on parameters of nasal patency were studied in vehicle-treated animals, as well as in the same animals pretreated 2 hours earlier with oral d-pseudoephedrine or chlorpheniramine. Local mast cell degranulation caused a close-related decrease in nasal cavity volume and minimal cross-sectional area (Amin) together with a highly variable increase in nasal secretions. Maximal responses were seen at 90-120 minutes after 48/80 administration. Oral administration of the adrenergic agonist, d-pseudoephedrine (3.0 mg/kg), significantly antagonized all of the nasal effects of compound 48/80 (3.0%). In contrast, oral administration of the histamine H1 receptor antagonist chlorpheniramine (10 mg/kg) appeared to reduce the increased nasal secretions but was without effect on the compound 48/ 80-induced nasal congestion (i.e., volume and Amin). These results show the effectiveness of using acoustic rhinometry in this anesthetized dog model. The observations that compound 48/80-induced nasal congestion was prevented by d-pseudoephedrine pretreatment, but not by chlorpheniramine, suggest that this noninvasive model system may provide an effective tool with which to study the actions of decongestant drugs in preclinical investigations.

Patient experience with mupirocin or povidone-iodine nasal decolonization.

PubMed

Maslow, Jed; Hutzler, Lorraine; Cuff, Germaine; Rosenberg, Andrew; Phillips, Michael; Bosco, Joseph

2014-06-01

Led by the federal government, the payers of health care are enacting policies designed to base provider reimbursement on the quality of care they render. This study evaluated and compared patient experiences and satisfaction with nasal decolonization with either nasal povidone-iodine (PI) or nasal mupirocin ointment (MO). A total of 1903 patients were randomized to undergo preoperative nasal decolonization with either nasal MO or PI solution. All randomized patients were also given 2% chlorhexidine gluconate topical wipes. Patients were interviewed prior to discharge to assess adverse events and patient experience with their assigned preoperative antiseptic protocol. Of the 1903 randomized patients, 1679 (88.1%) were interviewed prior to discharge. Of patients receiving PI, 3.4% reported an unpleasant or very unpleasant experience, compared with 38.8% of those using nasal MO (P<.0001). Sixty-seven percent of patients using nasal MO believed it to be somewhat or very helpful in reducing surgical site infections, compared with 71% of patients receiving PI (P>.05). Being recruited as an active participant in surgical site infection prevention was a positive experience for 87.2% of MO patients and 86.3% of PI patients (P=.652). Those assigned to receive PI solution preoperatively reported significantly fewer adverse events than the nasal MO group (P<.01). Preoperative nasal decolonization with either nasal PI or MO was considered somewhat or very helpful by more than two-thirds of patients. Copyright 2014, SLACK Incorporated.

External nasal dilators: definition, background, and current uses

PubMed Central

Dinardi, Ricardo Reis; de Andrade, Cláudia Ribeiro; Ibiapina, Cássio da Cunha

2014-01-01

Our goal was to revise the literature about external nasal dilators (ENDs) as to their definition, history, and current uses. We reviewed journals in the PubMed and MEDLINE databases. The current uses hereby presented and discussed are physical exercise, nasal congestion and sleep, snoring, pregnancy, cancer, and healthy individuals. Numerous studies have shown that ENDs increase the cross-sectional area of the nasal valve, reducing nasal resistance and transnasal inspiratory pressure and stabilizing the lateral nasal vestibule, avoiding its collapse during final inspiration. These effects also facilitate breathing and are beneficial to patients with nasal obstruction. Furthermore, END use is simple, noninvasive, painless, affordable, and bears minimum risk to the user. Most studies have limited sample size and are mainly focused on physical exercise. In conclusion, ENDs seem useful, so further studies involving potential effects on the performance of physical tests and improvements in sleep quality are necessary, especially in children and teenagers. PMID:25419156

Nasal reaction to changes in whole body temperature.

PubMed

Lundqvist, G R; Pedersen, O F; Hilberg, O; Nielsen, B

1993-11-01

The changes in nasal patency following a 1.5 degrees C decrease or increase in whole body temperature were measured in 8 healthy young males, during and after 30 min of immersion in a 15 degrees C cold or a 40 degrees C warm bath, breathing air at the same temperature, in a cross-over experimental design. The nasal reactions were traced by consecutive measurements of changes in nasal cavity volumes by acoustic rhinometry. Swelling of the mucosa during cooling and an almost maximal shrinkage of the mucosa during heating were indicated by respectively a decrease and an increase in nasal cavity volumes. The reactions were determined predominantly by the whole body thermal balance, but were also influenced by the temperature of the inhaled air, either enhanced, reduced or temporarily reversed. The greatest change occurred in the nasal cavity, left or right, which differed most from the final state at the beginning of exposure due to the actual state of nasal cycle.

Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal fibroblasts.

PubMed

Shin, Seung-Heon; Ye, Mi-Kyung; Choi, Sung-Yong; Kim, Yee-Hyuk

2016-06-01

Eosinophils and fibroblasts are known to play major roles in the pathogenesis of nasal polyps. Fungi are commonly found in nasal secretion and are associated with airway inflammation. To investigate whether activated eosinophils by airborne fungi can influence the production of extracellular matrix (ECM) from nasal fibroblasts. Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria or Aspergillus, respectively, for 24 hours and ECM messenger RNA (mRNA) and protein expressions were measured. Eosinophils isolated from healthy volunteers were stimulated with Alternaria or Aspergillus for 4 hours then superoxide, eosinophil peroxidase, and transforming growth factor β1 were measured. Then activated eosinophils were cocultured with nasal fibroblasts for 24 hours, and ECM mRNA expressions were measured. Alternaria strongly enhanced ECM mRNA expression and protein production from nasal fibroblasts. Alternaria also induced the production of superoxide, eosinophil peroxidase, and transforming growth factor β1 from eosinophils, and activated eosinophils enhanced ECM mRNA expression when they were cocultured without the Transwell insert system. Eosinophils activated with Alternaria enhanced ECM mRNA expression from nasal polyp fibroblasts. Alternaria plays an important role in tissue fibrosis in the pathogenesis of nasal polyps by directly or indirectly influencing the production of ECM from nasal fibroblasts. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Introduction for Design of Nanoparticle Based Drug Delivery Systems.

PubMed

Edgar, Jun Yan Chan; Wang, Hui

2017-01-01

Conventional drug delivery systems contain numerous limitations such as limited targeting, low therapeutic indices, poor water solubility, and the induction of drug resistances. In order to overcome the drawbacks of conventional pathway of drug delivery, nanoparticle delivery systems are therefore designed and used as the drug carriers. Nanoparticle based drug delivery systems have been rapidly growing and are being applied to various sections of biomedicine. Drug nanocarriers based on dendrimers, liposomes, self-assembling peptides, watersoluble polymers, and block copolymer micelles are the most extensively studied types of drug delivery systems and some of them are being used in clinical therapy. In particular for cancer therapy, antineoplastic drugs are taking advantage of nanoparticulate drug carriers to improve the cure efficacy. Nanoparticle based drug carriers are capable of improving the therapeutic effectiveness of the drugs by using active targeting for the site-specific delivery, passive targeting mechanisms such as enhanced permeability and retention (EPR), de novo synthesis and uptake of low density liposome in cancer cells or by being water-soluble to improve the suboptimal pharmacokinetics in limited water-soluble delivery methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of bilastine upon nasal obstruction.

PubMed

Dávila, I; Sastre, J; Mullol, J; Montoro, J; Jáuregui, I; Ferrer, M; del Cuvillo, A; Bartra, J; Valero, A

2011-01-01

H1 antihistamines constitute one of the main references for the treatment of allergic rhinitis. Classically, these drugs have been considered effective in controlling sneezing, rhinorrhea and itching, though they have not been regarded as particularly effective in application to nasal obstruction. The most recent studies, involving second-generation H1 antihistamines (desloratadine, fexofenadine, levocetirizine, rupatadine), have shown these drugs to offer effects upon nasal obstruction significantly superior to those of placebo. The present review examines the effect of bilastine, a new, potent and highly specific H1 antihistamine without sedative effects or cardiac toxicity, upon nasal obstruction. The analysis of the data from the different clinical trials indicates that in patients with allergic rhinitis, the effect of bilastine upon nasal obstruction is superior to that of placebo and similar to that of other second-generation H1 antihistamines, manifesting within 24 hours after the start of treatment.

Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery

PubMed Central

Gao, Weiwei; Zhang, Yue; Zhang, Qiangzhe; Zhang, Liangfang

2016-01-01

Nanoparticles have offered a unique set of properties for drug delivery including high drug loading capacity, combinatorial delivery, controlled and sustained drug release, prolonged stability and lifetime, and targeted delivery. To further enhance therapeutic index, especially for localized application, nanoparticles have been increasingly combined with hydrogels to form a hybrid biomaterial system for controlled drug delivery. Herein, we review recent progresses in engineering such nanoparticle-hydrogel hybrid system (namely ‘NP-gel’) with a particular focus on its application for localized drug delivery. Specifically, we highlight four research areas where NP-gel has shown great promises, including (1) passively controlled drug release, (2) stimuli-responsive drug delivery, (3) site-specific drug delivery, and (4) detoxification. Overall, integrating therapeutic nanoparticles with hydrogel technologies creates a unique and robust hybrid biomaterial system that enables effective localized drug delivery. PMID:26951462

Inhalation of diethylamine--acute nasal effects and subjective response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lundqvist, G.R.; Yamagiwa, M.; Pedersen, O.F.

1992-03-01

Adult volunteers were exposed to 25 ppm (75 mg/m3) diethylamine in a climate chamber for 15 min in order to study the acute nasal reactions to an exposure equivalent to the present threshold limit value-short-term exposure limit. Changes in nasal volume and nasal resistance were measured by acoustic rhinometry and by rhinomanometry. Acute change in nasal volume, usually seen as acute nasal mucosa response to thermal stimuli, was not observed, nor was an acute change in nasal airway resistance. In a subsequent experiment, the aim was to measure acute sensory effects. Exposure to a concentration increasing from 0 to 12more » ppm took place for 60 min, equal to an average concentration of 10 ppm (30 mg/m3). A moderate to strong olfactory response and distinct nasal and eye irritation were observed. In spite of considerable individual variation, the results were in agreement with sensory effect estimates obtained from animal studies.« less

Biotransformation enzymes in the rodent nasal mucosa: the value of a histochemical approach.

PubMed Central

Bogdanffy, M S

1990-01-01

An increasing number of chemicals have been identified as being toxic to the nasal mucosa of rats. While many chemicals exert their effects only after inhalation exposure, others are toxic following systemic administration, suggesting that factors other than direct deposition on the nasal mucosa may be important in mechanisms of nasal toxicity. The mucosal lining of the nasal cavity consists of a heterogeneous population of ciliated and nonciliated cells, secretory cells, sensory cells, and glandular and other cell types. For chemicals that are metabolized in the nasal mucosa, the balance between metabolic activation and detoxication within a cell type may be a key factor in determining whether that cell type will be a target for toxicity. Recent research in the area of xenobiotic metabolism in nasal mucosa has demonstrated the presence of many enzymes previously described in other tissues. In particular, carboxylesterase, aldehyde dehydrogenase, cytochromes P-450, epoxide hydrolase, and glutathione S-transferases have been localized by histochemical techniques. The distribution of these enzymes appears to be cell-type-specific and the presence of the enzyme may predispose particular cell types to enhanced susceptibility or resistance to chemical-induced injury. This paper reviews the distribution of these enzymes within the nasal mucosa in the context of their contribution to xenobiotic metabolism. The localization of the enzymes by histochemical techniques has provided important information on the potential mechanism of action of esters, aldehydes, and cytochrome P-450 substrates known to injure the nasal mucosa. Images PLATE 1. PLATE 2. PLATE 3. PMID:2200661

Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

PubMed Central

Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

2012-01-01

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

Economic evaluation of floseal compared to nasal packing for the management of anterior epistaxis.

PubMed

Le, Andre; Thavorn, Kednapa; Lasso, Andrea; Kilty, Shaun J

2018-01-04

To evaluate the cost-effectiveness of Floseal, a topically applied hemostatic agent, and nasal packing for the management of epistaxis in Canada. Outcomes research, a cost-utility analysis. We developed a Markov model to compare the costs and health outcomes of Floseal with nasal packing over a lifetime horizon from the perspective of a publicly funded healthcare system. A cycle length of 1 year was used. Efficacy of Floseal and packing was sought from the published literature. Unit costs were gathered from a hospital case costing system, whereas physician fees were extracted from the Ontario Schedule of Benefits for Physician Services. Results were expressed as an incremental cost per quality-adjusted life year (QALY) gained. A series of one-way sensitivity and probabilistic sensitivity analyses were performed. From the perspective of a publicly funded health are system, the Floseal treatment strategy was associated with higher costs ($2,067) and greater QALYs (0.27) than nasal packing. Our findings were highly sensitive to discount rates, the cost of Floseal, and the cost of nasal packing. The probabilistic sensitivity analysis suggested that the probability that Floseal treatment is cost-effective reached 99% if the willingness-to-pay threshold was greater than $120,000 per QALY gained. Prior studies have demonstrated Floseal to be an effective treatment for anterior epistaxis. In the Canadian healthcare system, Floseal treatment appears to be a cost-effective treatment option compared to nasal packing for anterior epistaxis. 2c Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B.

PubMed

Khatri, Kapil; Goyal, Amit K; Gupta, Prem N; Mishra, Neeraj; Vyas, Suresh P

2008-04-16

This work investigates the preparation and in vivo efficacy of plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B. Chitosan pDNA nanoparticles were prepared using a complex coacervation process. Prepared nanoparticles were characterized for size, shape, surface charge, plasmid loading and ability of nanoparticles to protect DNA against nuclease digestion and for their transfection efficacy. Nasal administration of nanoparticles resulted in serum anti-HBsAg titre that was less compared to that elicited by naked DNA and alum adsorbed HBsAg, but the mice were seroprotective within 2 weeks and the immunoglobulin level was above the clinically protective level. However, intramuscular administration of naked DNA and alum adsorbed HBsAg did not elicit sIgA titre in mucosal secretions that was induced by nasal immunization with chitosan nanoparticles. Similarly, cellular responses (cytokine levels) were poor in case of alum adsorbed HBsAg. Chitosan nanoparticles thus produced humoral (both systemic and mucosal) and cellular immune responses upon nasal administration. The study signifies the potential of chitosan nanoparticles as DNA vaccine carrier and adjuvant for effective immunization through non-invasive nasal route.

Porous Inorganic Drug Delivery Systems-a Review.

PubMed

Sayed, E; Haj-Ahmad, R; Ruparelia, K; Arshad, M S; Chang, M-W; Ahmad, Z

2017-07-01

Innovative methods and materials have been developed to overcome limitations associated with current drug delivery systems. Significant developments have led to the use of a variety of materials (as excipients) such as inorganic and metallic structures, marking a transition from conventional polymers. Inorganic materials, especially those possessing significant porosity, are emerging as good candidates for the delivery of a range of drugs (antibiotics, anticancer and anti-inflammatories), providing several advantages in formulation and engineering (encapsulation of drug in amorphous form, controlled delivery and improved targeting). This review focuses on key selected developments in porous drug delivery systems. The review provides a short broad overview of porous polymeric materials for drug delivery before focusing on porous inorganic materials (e.g. Santa Barbara Amorphous (SBA) and Mobil Composition of Matter (MCM)) and their utilisation in drug dosage form development. Methods for their preparation and drug loading thereafter are detailed. Several examples of porous inorganic materials, drugs used and outcomes are discussed providing the reader with an understanding of advances in the field and realistic opportunities.

Effect of formulation- and administration-related variables on deposition pattern of nasal spray pumps evaluated using a nasal cast.

PubMed

Kundoor, Vipra; Dalby, Richard N

2011-08-01

To systematically evaluate the effect of formulation- and administration-related variables on nasal spray deposition using a nasal cast. Deposition pattern was assessed by uniformly coating a transparent nose model with Sar-Gel®, which changes from white to purple on contact with water. Sprays were subsequently discharged into the cast, which was then digitally photographed. Images were quantified using Adobe® Photoshop. The effects of formulation viscosity (which influences droplet size), simulated administration techniques (head orientation, spray administration angle, spray nozzle insertion depth), spray pump design and metering volume on nasal deposition pattern were investigated. There was a significant decrease in the deposition area associated with sprays of increasing viscosity. This appeared to be mediated by an increase in droplet size and a narrowing of the spray plume. Administration techniques and nasal spray pump design also had a significant effect on the deposition pattern. This simple color-based method provides quantitative estimates of the effects that different formulation and administration variables may have on the nasal deposition area, and provides a rational basis on which manufacturers of nasal sprays can base their patient instructions or post approval changes when it is impractical to optimize these using a clinical study.

Efficacy of INSURE during nasal CPAP in preterm infants with respiratory distress syndrome.

PubMed

Leone, F; Trevisanuto, D; Cavallin, F; Parotto, M; Zanardo, V

2013-04-01

INSURE (INtubation, SURfactant, Extubation) is a proven complement of nasal CPAP (nCPAP) for respiratory distress syndrome (RDS) treatment of preterm infants. Early administration is characterized by greater success. We aimed to determine the efficacy and failure or other respiratory outcomes of INSURE administration during nasal continous positive airway pressure (nCPAP) treatment of RDS. Among 824 premature infants neonatal intensive care unit (NICU) admitted at Padua University Hospital during 2007-2009, 209 (25.4%) were managed by surfactant replacement (200 mg/kg, Curosurf®) if required >45% oxygen ("rescue" treatment), including 42 (20.1%) during nCPAP. Each premature infant treated with INSURE during nasal CPAP was compared to 2 consecutive control infants treated with surfactant during mechanical ventilation, matched for antenatal steroids, delivery route, gestational age, and sex. Infants with RDS, treated with nCPAP and INSURE-complement (N.=25), were comparable in Apgar score, need of PPV at birth, birth weight, pre-surfactant FiO2 and timing of surfactant replacement to controls. However, nCPAP and INSURE-complement was superior in terms both of oxygenation, evaluated as post-treatment FiO2 (Median, [IQR], 26 [21-40] vs. 21 [21-29]; P=0.03) and (a-A) pO2 (0.48 [0.45-0.60] vs. 0.58 [0.53-0.72]; P=0.03). The improved oxygenation was sustained over the following days. In addition, premature infants treated with nCPAP and INSURE-complement developed less respiratory co-morbidities, including pneumothorax, borncopulmonary disease (BPD), and BPD and death (P=0.04). INSURE-complement of nasal CPAP has a superior efficacy in terms of oxygenation improvement, maintenance of optimal oxygenation, and reduction of respiratory comorbidities respect to "rescue" surfactant administration during mechanical ventilation.

Nasal cycle dominance and hallucinations in an adult schizophrenic female.

PubMed

Shannahoff-Khalsa, David; Golshan, Shahrokh

2015-03-30

Nasal dominance, at the onset of hallucinations, was studied as a marker of both the lateralized ultradian rhythm of the autonomic nervous system and the tightly coupled ultradian rhythm of alternating cerebral hemispheric dominance in a single case study of a schizophrenic female. Over 1086 days, 145 hallucination episodes occurred with left nostril dominance significantly greater than the right nostril dominant phase of the nasal cycle. A right nostril breathing exercise, that primarily stimulates the left hemisphere, reduces symptoms more quickly for hallucinations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficiency performance of China's health care delivery system.

PubMed

Zhang, Luyu; Cheng, Gang; Song, Suhang; Yuan, Beibei; Zhu, Weiming; He, Li; Ma, Xiaochen; Meng, Qingyue

2017-07-01

Improving efficiency performance of the health care delivery system has been on the agenda for the health system reform that China initiated in 2009. This study examines the changes in efficiency performance and determinants of efficiency after the reform to provide evidence to assess the progress of the reform from the perspective of efficiency. Descriptive analysis, Data Envelopment Analysis, the Malmquist Index, and multilevel regressions are used with data from multiple sources, including the World Bank, the China Health Statistical Yearbook, and routine reports. The results indicate that over the last decade, health outcomes compared with health investment were relatively higher in China than in most other countries worldwide, and the trend was stable. The overall efficiency and total factor productivity increased after the reform, indicating that the reform was likely to have had a positive impact on the efficiency performance of the health care delivery system. However, the health care delivery structure showed low system efficiency, mainly attributed to the weakened primary health care system. Strengthening the primary health care system is central to enhancing the future performance of China's health care delivery system. Copyright © 2017 John Wiley & Sons, Ltd.

Current and emerging lipid-based systems for transdermal drug delivery.

PubMed

Singla, Sumeet K; Sachdeva, Vishal

2015-01-01

Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

Impact of different nasal masks on CPAP therapy for obstructive sleep apnea: a randomized comparative trial.

PubMed

Neuzeret, Pierre-Charles; Morin, Laurent

2017-11-01

Patient interface is important for the success of continuous positive airway pressure (CPAP), but few trials have examined the influence of mask choice on CPAP adherence. To compare the impact of different nasal masks on CPAP in patients with newly-diagnosed obstructive sleep apnea (OSA). OSA patients were randomized in a 2:3 ratio to receive CPAP via different first-line nasal masks: ResMed Mirage FX® (MFX) or control mask (Fisher & Paykel Zest ® , HC407 ® or Philips EasyLife ® ). Mask acceptance, CPAP compliance and Home Care Provider (HCP) interventions were compared between groups after 3 months of CPAP therapy using modified intent-to-treat (mITT; after exclusion of patients with mouth leaks during CPAP initiation) and on-treatment (OT; CPAP adherent) analyses. Of 285 randomized patients, 90 requiring a full-face mask were excluded, leaving 195 and 151 in the mITT and OT analyses, respectively. Mask acceptance rate was higher in the MFX versus control group (mITT: 79% vs 68%, P = 0.067; OT: 90% vs 76%, P = 0.022). CPAP compliance was higher (5.9 ± 1.8 vs 5.1 ± 1.6 h/night, P = 0.011) and nasal mask issue-related HCP visits lower (3% vs 17%, P = 0.006) in the MFX group. Nasal mask failures due to mask discomfort (5% vs 1%) or unintentional leakage (5% vs 0%) were higher in control vs MFX group. Mask acceptance was significantly associated with fewer mask leaks (P = 0.002) and higher pressure therapy (P = 0.042). This study highlights differences between nasal masks for CPAP delivery and shows that initial mask selection can influence adherence and healthcare utilization during CPAP. © 2016 ResMed Germany Inc. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.

Effect of early correction of nasal septal deformity in unilateral cleft lip and palate on inferior turbinate hypertrophy and nasal patency.

PubMed

Pinto, Valentina; Piccin, Ottavio; Burgio, Luca; Summo, Valeria; Antoniazzi, Elisa; Morselli, Paolo G

2018-05-01

A relatively neglected aspect of cleft lip nasal deformity is the effect of septal deviation and inferior turbinate hypertrophy (ITH) on the functional airway. In particular, ITH in the noncleft side can be especially problematic, because it reduces the healthy nasal area, creating bilateral nasal obstruction that might affect the growth of the maxillofacial skeleton. Although these anatomic and functional changes are documented, few recommendations have been developed regarding the proper approach to ITH. The aim of the present study was to asses the ITH severity and determine the degree of nasal airway patency in patients who have undergone primary correction of the nasal septum during lip repair compared to patients operated on without primary septal correction. The study population included two groups. One group consisted of twenty unilateral cleft lip palate UCLP patients who have previously undergone primary rhinoseptoplasty as part of their treatment plan. The control group consisted of twenty UCLP patients operated on without rhinoseptal correction. The Nasal Obstructive Symptom Evaluation (NOSE) scale and nasal endoscopy were used to assess nasal obstruction. The overall untreated group reported severe symptoms across all NOSE scale dimensions more frequently than children who have undergone primary rhinoseptoplasty. The difference was statistically significant for each dimensions (p < 0.05). The mean NOSE score for group A and group B was 21.4 ± 9.4 and 70.8 ± 17.2 respectively (p < 0.0001). In group A turbinate size decreased significantly (p < 0.05) compared to pre-operative data. Comparing the two groups a statistically significant difference in turbinate size was observed (p < 0.0001). The results of the present study confirm that there is a significant degree of ITH and nasal airway dysfunction in patients with UCLP. Early septal repositioning during primary cleft lip repair results in a statistically significant reduction in IT

Nanomaterials in cancer-therapy drug delivery system.

PubMed

Zhang, Gen; Zeng, Xin; Li, Ping

2013-05-01

Nanomaterials can enhance the delivery and treatment efficiency of anti-cancer drugs, and the mechanisms of the tumor-reducing activity of nanomaterials with cancer drug have been investigated. The task for drug to reach pathological areas has facilitated rapid advances in nanomedicine. Herein, we summarize promising findings with respect to cancer therapeutics based on nano-drug delivery vectors. Relatively high toxicity of uncoated nanoparticles restricts the use of these materials in humans. In order to reduce toxicity, many approaches have focused on the encapsulation of nanoparticles with biocompatible materials. Efficient delivery systems have been developed that utilized nanoparticles loaded with high dose of cancer drug in the presence of bilayer molecules. Well-established nanotechnologies have been designed for drug delivery with specific bonding. Surface-modified nanoparticles as vehicles for drug delivery system that contains multiple nano-components, each specially designed to achieve aimed task for the emerging application delivery of therapeutics. Drug-coated polymer nanoparticles could efficiently increase the intracellular accumulation of anti-cancer drugs. This review also introduces the nanomaterials with drug on the induction of apoptosis in cancer cells in vitro and in vivo. Direct interactions between the particles and cellular molecules to cause adverse biological responses are also discussed.

A retrospective study of chronic nasal disease in 75 dogs.

PubMed

Lobetti, R G

2009-12-01

Chronic nasal disease is a common problem in dogs. To determine the aetiology, a retrospective study in 75 dogs with persistent and chronic nasal disease was done. All dogs were evaluated by means of survey nasal radiographs, antegrade and retrograde rhinoscopy, bacterial and fungal cultures, and histopathology. A definitive diagnosis was made in 74/75 cases (98.6%). Nasal neoplasia was the most common diagnosis (46.7%), median age 108 months, followed by lympho-plasmacytic rhinitis (20%), median age 112 months, and fungal rhinitis (10.7%), median age 53.5 months. Other diagnoses included nasal foreign body (5.3%), median age 51 months, and primary bacterial rhinitis (6.7%), median age 116.5 months. Rare aetiologies identified were nasal polyps, granulomatous rhinitis, oro-nasal fistula and naso-pharyngeal stenosis. This study showed that by using a structured combination of survey radiography, rhinoscopy, cultures and histopathology, a diagnosis could be made in dogs with chronic nasal disease.

Nasal reconstruction after epithelioma.

PubMed

Rodríguez-Camps, S

2001-01-01

In this paper we present our procedure for the treatment, histopathological diagnosis, and resection of skin cancer in the nasal pyramid and its subsequent reconstruction. Because we are dealing with the most important anatomical feature of the face our goal is an aesthetic reconstruction [2,4] according to the anatomical subunits criterion of Burget [3]. First, a histopathological diagnosis is made to determine the nature of the tumor. Then, we proceed with the resection according to the Mohs Micrographic Surgery [1,5,7]. Then we begin with the first step of the nasal reconstruction.

A Comparison of Over-the-Counter Mechanical Nasal Dilators: A Systematic Review.

PubMed

Kiyohara, Nicole; Badger, Christopher; Tjoa, Tjoson; Wong, Brian

2016-09-01

The internal nasal valve is the narrowest part of the nasal airway and a common site of inspiratory collapse and obstruction of nasal airflow. Over-the-counter mechanical nasal dilators are an alternative to surgical intervention that attempts to improve airflow through the internal nasal valve. To determine the efficacy of over-the-counter mechanical nasal dilators and classify these products by mechanism. A database of 33 available over-the-counter mechanical nasal dilators was generated via a PubMed search as well as an internet search via Amazon.com and Google, conducted from April 1, 2013, through December 31, 2015. Products determined to be unavailable or discontinued were excluded from the database. Of the devices examined in published literature, efficacy was based on objective measures, such as measured airflow, the cross-sectional area of the nasal valve, and changes in resistance. Measures of reported sleep quality or patient perception were excluded. An analysis of each product's mechanism revealed 4 broad classes: external nasal dilator strips, nasal stents, nasal clips, and septal stimulators. A review demonstrated 5 studies supporting the use of external nasal dilator strips, 4 studies supporting the use of nasal clips, 1 study supporting the use of nasal stents, and no studies supporting the use of septal stimulators. Our findings suggest that external nasal dilator strips and nasal clips effectively relieve obstruction of the internal nasal valve and may be an alternative to surgical intervention in some patients.

Dialectal and gender differences in nasalance for a Mandarin population.

PubMed

Kim, Ha-Kyung; Yu, Xiao-meng; Cao, Yan-jing; Liu, Xiao-ming; Huang, Zhao-Ming

2016-01-01

The purpose of this study was to determine whether there are dialectal and gender related differences in nasalance of main Mandarin vowels and three sentences in 400 Chinese normal adults. The mean nasalance score difference for dialect and gender was significant (p < .001) in all speech materials. For different dialects, the average nasalance scores show that Chongqing > Beijing > Shanghai > Guangzhou for the nasal sentence, oro-nasal sentence, /a/, /i/ and /u/. In addition, the average nasalance scores of females were higher than those of males for all speech materials in all dialects. The clinical significance of this study can be helpful in making nasalance clinical decisions for Chinese people with cleft palate, hearing disorders and dysarthria with resonance disorders. It also shows the theoretical and socio-cultural features for linguists considering dialects and gender.

The Effect of Menstrual Cycle on Nasal Resonance Characteristics in Females

ERIC Educational Resources Information Center

Kumar, Suman; Basu, Shriya; Sinha, Anisha; Chatterjee, Indranil

2012-01-01

The purpose of this study was to analyze resonance characteristics (nasality and nasalance values) during the menstrual cycle. Previous studies indicate changes in voice quality and nasal mucosa due to temporary falling estrogen levels in human females during their menstrual cycle. The present study compared the nasality and "nasalance scores"…

[Objective measurement of normal nasality in the Saxony dialect].

PubMed

Müller, R; Beleites, T; Hloucal, U; Kühn, M

2000-12-01

In the United States of America, the nasometer was developed by Fletcher as an objective method for measuring nasality. There are no accepted normal values for comparable test materials regarding the German language. The aim of this study was the examination of the auditively normal nasality of Saxon-speaking people with the nasometer. The nasalance of 51 healthy Saxon-speaking test persons with auditively normal nasality was measured with a model 6200 nasometer (Kay-Elemetrics, U.S.A.). The text materials used were the vowels "a", "e", "i", "o", and "u", the sentences "Die Schokolade ist sehr lecker" ("The chocolate is very tasty") and "Nenne meine Mama Mimi" ("Name my mama Mimi"), and the texts of "North wind and sun", "A children's birthday", and an arbitrary selection from Strittmatter. The mean nasalance for the vowels was 17.7%, for the sentence containing no nasal sounds 13.0%, and for the sentence containing many nasal sounds 67.2%. The mean value of the texts was 33-41%. The results for the texts agreed well with the results of Reuter (1997), who examined people from the state of Brandenburg. A range from 20% to 55% is suggested as the normal value for nasalance in the German-speaking area.

A Nasal Brush-based Classifier of Asthma Identified by Machine Learning Analysis of Nasal RNA Sequence Data.

PubMed

Pandey, Gaurav; Pandey, Om P; Rogers, Angela J; Ahsen, Mehmet E; Hoffman, Gabriel E; Raby, Benjamin A; Weiss, Scott T; Schadt, Eric E; Bunyavanich, Supinda

2018-06-11

Asthma is a common, under-diagnosed disease affecting all ages. We sought to identify a nasal brush-based classifier of mild/moderate asthma. 190 subjects with mild/moderate asthma and controls underwent nasal brushing and RNA sequencing of nasal samples. A machine learning-based pipeline identified an asthma classifier consisting of 90 genes interpreted via an L2-regularized logistic regression classification model. This classifier performed with strong predictive value and sensitivity across eight test sets, including (1) a test set of independent asthmatic and control subjects profiled by RNA sequencing (positive and negative predictive values of 1.00 and 0.96, respectively; AUC of 0.994), (2) two independent case-control cohorts of asthma profiled by microarray, and (3) five cohorts with other respiratory conditions (allergic rhinitis, upper respiratory infection, cystic fibrosis, smoking), where the classifier had a low to zero misclassification rate. Following validation in large, prospective cohorts, this classifier could be developed into a nasal biomarker of asthma.

Seven Ventilators Challenged With Leaks During Neonatal Nasal CPAP: An Experimental Pilot Study.

PubMed

Drevhammar, Thomas; Nilsson, Kjell; Zetterström, Henrik; Jonsson, Baldvin

2015-07-01

Nasal CPAP is the most common respiratory support for neonates. Several factors are considered important for effective treatment, including leaks at the patient interface and the delivery of pressure-stable CPAP. Investigations of pressure stability during leaks should include both the change in the mean delivered CPAP and the pressure variation during each breath. The aim of this study was to examine the response of ventilators delivering nasal CPAP when challenged with leaks at the patient interface. Seven ventilators providing nasal CPAP at 4 cm H2O were challenged with leaks during simulated neonatal breathing. Leak was applied for 15 consecutive breaths at a constant level (1-4 L/min). The 2 aspects of pressure stability were evaluated by measuring the mean delivered CPAP and the amplitude of pressure swings before, during, and after leaks. The ability to maintain the delivered CPAP and the amplitude of pressure swings varied greatly among the 7 ventilators before, during, and after leaks. Four of the ventilators tested have built-in leak compensation. There was no simple relationship between maintaining delivered CPAP during leaks and providing CPAP with low pressure swing amplitude. Maintaining the delivered CPAP and providing this without pressure swings are 2 separate aspects of pressure stability, and investigations concerning the clinical importance of pressure stability should address both aspects. This study also shows that compensation for leaks does not necessarily provide pressure-stable CPAP. Copyright © 2015 by Daedalus Enterprises.

Disposition of nasal, intravenous, and oral methadone in healthy volunteers.

PubMed

Dale, Ola; Hoffer, Christine; Sheffels, Pamela; Kharasch, Evan D

2002-11-01

Nasal administration of many opioids demonstrates rapid uptake and fast onset of action. Nasal administration may be an alternative to intravenous and oral administration of methadone and was therefore studied in human volunteers. The study was approved by the Institutional Review Board of the University of Washington, Seattle. Eight healthy volunteers (6 men and 2 women) aged 19 to 33 years were enrolled after informed written consent was obtained. Subjects received 10 mg methadone hydrochloride nasally, orally, or intravenously on 3 separate occasions in a crossover design. Nasal methadone (50 mg/mL in aqueous solution) was given as a 100-microL spray in each nostril (Pfeiffer BiDose sprayer). Blood samples for liquid chromatography-mass spectrometry analyses of methadone and the metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were drawn for up to 96 hours. The methadone effect was measured by noninvasive infrared pupilometry coincident with blood sampling. Nasal uptake of methadone was rapid, with maximum plasma concentrations occurring within 7 minutes. The maximum effects of intravenous, nasal, and oral methadone, on the basis of dark-adapted pupil diameter, were reached in about 15 minutes, 30 minutes, and 2 hours, respectively. The respective durations were 24, 10, and 8 hours. Both nasal and oral bioavailabilities were 0.85. Subjects reported that nasal methadone caused a burning sensation. Nasal administration of methadone results in rapid absorption and onset of effect and high bioavailability, which was greater than that reported for other nasal opioids, with a similar duration of effect. Nasal administration may be an alternative route of methadone administration; however, improved formulations are desirable to reduce nasal irritation.

Nasal septal angiofibroma, a subclass of extranasopharyngeal angiofibroma.

PubMed

Garcia-Rodriguez, Laura; Rudman, Kelli; Cogbill, Christopher H; Loehrl, Todd; Poetker, David M

2012-01-01

Extranasopharyngeal angiofibromas (ENA) arising from the nasal septum or nasal septal angiofibromas are extremely rare; only 13 such cases have been reported in the international literature. Our objective is to describe the presentation, workup, and surgical management of these lesions. Case reports were done. The setting was a tertiary care referral center and the Veterans Affairs Medical Center. PATIENTS, INTERVENTIONS, AND RESULTS: We present 2 cases of extranasopharyngeal angiofibroma occurring on the nasal septum. In this report, we discuss the occurrence, the histopathologic findings, and the treatment of nasal septal angiofibroma. Copyright © 2012 Elsevier Inc. All rights reserved.

Nasal Anatomy

MedlinePlus

... below. The nasal cavity is surrounded by paired, air-filled chambers on each side, and these lie towards the ... and left “choana” and open into a common chamber called the ... When we breathe in, air travels through the nostril, through the right and ...

Effort of breathing in children receiving high-flow nasal cannula.

PubMed

Rubin, Sarah; Ghuman, Anoopindar; Deakers, Timothy; Khemani, Robinder; Ross, Patrick; Newth, Christopher J

2014-01-01

High-flow humidified nasal cannula is often used to provide noninvasive respiratory support in children. The effect of high-flow humidified nasal cannula on effort of breathing in children has not been objectively studied, and the mechanism by which respiratory support is provided remains unclear. This study uses an objective measure of effort of breathing (Pressure. Rate Product) to evaluate high-flow humidified nasal cannula in critically ill children. Prospective cohort study. Quaternary care free-standing academic children's hospital. ICU patients younger than 18 years receiving high-flow humidified nasal cannula or whom the medical team planned to extubate to high-flow humidified nasal cannula within 72 hours of enrollment. An esophageal pressure monitoring catheter was placed to measure pleural pressures via a Bicore CP-100 pulmonary mechanics monitor. Change in pleural pressure (ΔPes) and respiratory rate were measured on high-flow humidified nasal cannula at 2, 5, and 8 L/min. ΔPes and respiratory rate were multiplied to generate the Pressure.Rate Product, a well-established objective measure of effort of breathing. Baseline Pes, defined as pleural pressure at end exhalation during tidal breathing, reflected the positive pressure generated on each level of respiratory support. Twenty-five patients had measurements on high-flow humidified nasal cannula. Median age was 6.5 months (interquartile range, 1.3-15.5 mo). Median Pressure,Rate Product was lower on high-flow humidified nasal cannula 8 L/min (median, 329 cm H2O·min; interquartile range, 195-402) compared with high-flow humidified nasal cannula 5 L/min (median, 341; interquartile range, 232-475; p = 0.007) or high-flow humidified nasal cannula 2 L/min (median, 421; interquartile range, 233-621; p < 0.0001) and was lower on high-flow humidified nasal cannula 5 L/min compared with high-flow humidified nasal cannula 2 L/min (p = 0.01). Baseline Pes was higher on high-flow humidified nasal

Response characteristics for thermal and pressure devices commonly used for monitoring nasal and oral airflow during sleep studies.

PubMed

Gehring, J M; Cho, J-G; Wheatley, J R; Amis, T C

2014-03-01

We examined thermocouple and pressure cannulae responses to oral and nasal airflow using a polyester model of a human face, with patent nasal and oral orifices instrumented with a dual thermocouple (F-ONT2A, Grass) or a dual cannula (0588, Braebon) pressure transducer (± 10 cm H2O, Celesco) system. Tidal airflow was generated using a dual compartment facemask with pneumotachographs (Fleisch 2) connected to the model orifices. During nasal breathing: thermocouple amplitude = 0.38 Ln [pneumotachograph amplitude] + 1.31 and pressure cannula amplitude = 0.93 [pneumotachograph amplitude](2.15); during oral breathing: thermocouple amplitude = 0.44 Ln [pneumotachograph amplitude] + 1.07 and pressure cannula amplitude = 0.33 [pneumotachograph amplitude](1.72); (all range ∼ 0.1-∼ 4.0 L s(-1); r(2) > 0.7). For pneumotachograph amplitudes <1 L s(-1) (linear model) change in thermocouple amplitude/unit change in pneumotachograph amplitude was similar for nasal and oral airflow, whereas nasal pressure cannula amplitude/unit change in pneumotachograph amplitude was almost four times that for oral. Increasing oral orifice area from 0.33 cm(2) to 2.15 cm(2) increased oral thermocouple amplitude/unit change in pneumotachograph amplitude by ∼ 58% but decreased pressure cannula amplitude/unit change in pneumotachograph amplitude by 49%. For pneumotachograph amplitudes up to 1 L s(-1), alterations in inspiratory/expiratory ratios or total respiratory time did not affect the sensitivity of either nasal or oral pressure cannulae or the nasal thermocouple, but the oral thermocouple sensitivity was influenced by respiratory cycle time. Different nasal and oral responses influence the ability of these systems to quantitatively assess nasal and oral airflow and oro-nasal airflow partitioning.

New Delivery Systems for the 21st Century.

ERIC Educational Resources Information Center

Van Patten, James J.

This paper presents an historical perspective on the development of educational delivery systems, and then turns to the challenges of the information age and the issues of developing new delivery systems in this challenging environment. The paper discusses the fragility of power sources and of the networked world; technological weaknesses; freedom…

Nasal hydropulsion: a novel tumor biopsy technique.

PubMed

Ashbaugh, Elizabeth A; McKiernan, Brendan C; Miller, Carrie J; Powers, Barbara

2011-01-01

Intranasal tumors of dogs and cats pose a diagnostic and therapeutic challenge for small animal practitioners. Multiple nasal biopsy techniques have been described in the past. This report describes a simplified flushing technique to biopsy and debulk nasal tumors, which often also results in immediate clinical relief for the patient. Based on the results of this retrospective study, the authors recommend high-pressure saline hydropulsion as a minimally invasive diagnostic, and potentially therapeutic, technique for nasal tumors in dogs and cats.

Stability of extemporaneously prepared preservative-free prochlorperazine nasal spray.

PubMed

Yellepeddi, Venkata K

2018-01-01

The stability of an extemporaneously prepared preservative-free prochlorperazine 5-mg/mL nasal spray was evaluated. The preservative-free prochlorperazine nasal spray was prepared by adding 250 mg of prochlorperazine edisylate to 50 mL of citrate buffer in a low-density polyethylene nasal spray bottle. A stability-indicating high-performance liquid chromatography (HPLC) method was developed and validated using the major degradant prochlorperazine sulfoxide and by performing forced-degradation studies. For chemical stability studies, 3 100-μL samples of the preservative-free prochlorperazine from 5 nasal spray bottles stored at room temperature were collected at days 0, 20, 30, 45, and 60 and were assayed in triplicate using the stability-indicating HPLC method. Microbiological testing involved antimicrobial effectiveness testing based on United States Pharmacopeia ( USP ) chapter 51 and quantitative microbiological enumeration of aerobic bacteria, yeasts, and mold based on USP chapter 61. Samples for microbiological testing were collected at days 0, 30, and 60. The stability-indicating HPLC method clearly identified the degradation product prochlorperazine sulfoxide without interference from prochlorperazine. All tested solutions retained over 90% of the initial prochlorperazine concentration for the 60-day study period. There were no detectable changes in color, pH, and viscosity in any sample. There was no growth of bacteria, yeast, and mold for 60 days in all samples tested. An extemporaneously prepared preservative-free nasal spray solution of prochlorperazine edisylate 5 mg/mL was physically, chemically, and microbiologically stable for 60 days when stored at room temperature in low-density polyethylene bottles. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Strategies for drug delivery to the central nervous system by systemic route.

PubMed

Kasinathan, Narayanan; Jagani, Hitesh V; Alex, Angel Treasa; Volety, Subrahmanyam M; Rao, J Venkata

2015-05-01

Delivery of a drug into the central nervous system (CNS) is considered difficult. Most of the drugs discovered over the past decade are biological, which are high in molecular weight and polar in nature. The delivery of such drugs across the blood-brain barrier presents problems. This review discusses some of the options available to reach the CNS by systemic route. The focus is mainly on the recent developments in systemic delivery of a drug to the CNS. Databases such as Scopus, Google scholar, Science Direct, SciFinder and online journals were referred for preparing this article including 89 references. There are at least nine strategies that could be adopted to achieve the required drug concentration in the CNS. The recent developments in drug delivery are very promising to deliver biologicals into the CNS.

Nasal aesthetics: a cross-cultural analysis.

PubMed

Broer, Peter N; Buonocore, Samuel; Morillas, Angie; Liu, Jong; Tanna, Neil; Walker, Marc; Ng, Reuben; Ng, Ruben; Persing, John A

2012-12-01

Plastic surgeons often approach nasal aesthetic evaluation with the aid of seemingly objective measurements. However, ideal measurements of an attractive nose, as suggested in the literature, might not apply on a cross-cultural basis. Given these controversies, this study aimed to investigate the cultural and ethnic impact on nasal shape preferences. Computerized images of a model's nose were generated in which the nasal width, root, tip, dorsum, and projection of the lips and chin could be altered. A survey containing these images was sent to over 13,000 plastic surgeons and lay people in 50 different countries, with a total response rate of 9.6 percent. Demographic information about the interviewees was obtained. Preferred dimensions of the nose were broken down according to geographic, ethnic, occupational, and sex variables. Interregional comparison revealed that plastic surgeons from Latin America and the Caribbean overall prefer smaller and narrower noses, with more projecting tips, lips, and chins. Similar trends hold true when analyzing results from the general public. Significant differences were found comparing preferences between plastic surgeons and the general public. Plastic surgeons preferred wider nasal roots and tips and, in combination, more projected nasal dorsi, tips, lips, and chins. No universal parameter can define ideal aesthetics of the nose across cultures and ethnic backgrounds. As demonstrated, geographic, ethnic, and cultural factors influence aesthetic perceptions of patients and surgeons.

Airflow, gas deposition, and lesion distribution in the nasal passages.

PubMed Central

Morgan, K T; Monticello, T M

1990-01-01

The nasal passages of laboratory animals and man are complex, and lesions induced in the delicate nasal lining by inhaled air pollutants vary considerably in location and nature. The distribution of nasal lesions is generally a consequence of regional deposition of the inhaled material, local tissue susceptibility, or a combination of these factors. Nasal uptake and regional deposition are are influenced by numerous factors including the physical and chemical properties of the inhaled material, such as water solubility and reactivity; airborne concentration and length of exposure; the presence of other air contaminants such as particulate matter; nasal metabolism, and blood and mucus flow. For certain highly water-soluble or reactive gases, nasal airflow patterns play a major role in determining lesion distribution. Studies of nasal airflow in rats and monkeys, using casting and molding techniques combined with a water-dye model, indicate that nasal airflow patterns are responsible for characteristic differences in the distribution of nasal lesions induced by formaldehyde in these species. Local tissue susceptibility is also a complex issue that may be a consequence of many factors, including physiologic and metabolic characteristics of the diverse cell populations that comprise each of the major epithelial types lining the airways. Identification of the principal factors that influence the distribution and nature of nasal lesions is important when attempting the difficult process of determining potential human risks using data derived from laboratory animals. Toxicologic pathologists can contribute to this process by carefully identifying the site and nature of nasal lesions induced by inhaled materials. Images FIGURE 4. FIGURE 6. FIGURE 7. PMID:2200663

Anatomy of the nasal profile

PubMed Central

Anderson, K J; Henneberg, M; Norris, R M

2008-01-01

There is a lack in the understanding of the variation within the thickness of the soft tissue structures (muscle, skin and fat) overlying the cartilaginous skeleton of the nose and their relationship to the dorsum shape. We examined such relationships by dissecting noses of six adult female and six adult male cadavers, comparing the internal anatomical structures to the external nasal profile. We found that the soft tissue structures differ in thickness along the dorsum and that these differences are individualized. Specifically, continuous presence of subcutaneous fat from root to tip was found in half the sample, one nose had fat only on the tip, another one only on the root, the four others at both positions. The nasalis muscle was identifiable in nine of the 12 noses, transversing the nose in half the sample, and in the remaining three, only the lateral section of the muscle was identified. The superior border of the septal cartilage does not form a linear extension of the profile contour of the nasal bones but angles downwards. The actual profile contour of the dorsum does not follow the profile of the nasal bones or the septal cartilage. These results may influence the current use of nasal guidelines in forensic facial approximation. PMID:19172735

NORMAL NASAL GENE EXPRESSION LEVELS USING CDNA ARRAY TECHNOLOGY

EPA Science Inventory

Normal Nasal Gene Expression Levels Using cDNA Array Technology.

The nasal epithelium is a target site for chemically-induced toxicity and carcinogenicity. To detect and analyze genetic events which contribute to nasal tumor development, we first defined the gene expressi...

Biomimetics in drug delivery systems: A critical review.

PubMed

Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

2017-05-10

Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

[Nasal flaring as a predictor of mortality in patients with severe dyspnea].