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Intranasal delivery

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https://www.readbyqxmd.com/read/28521670/intranasal-drug-delivery-a-non-invasive-approach-for-the-better-delivery-of-neurotherapeutics
#1
Umesh Gupta, Hitesh Kumar, Gaurav Mishra, Ashok Kumar Sharma, Avinash Gothwal, Prashant Kesharwani
BACKGROUND: The convoluted pathophysiology of brain disorders along with penetration issue of drugs to brain represents major hurdle that requires some novel therapies. The blood-brain barrier (BBB) denotes a rigid barrier for delivery of therapeutics in vivo, to overcome this barrier intranasal delivery is an excellent strategy to deliver the drug directly to brain via olfactory and trigeminal nerve pathways that originate as olfactory neuro-epithelium in the nasal cavity and terminate in brain...
May 14, 2017: Pharmaceutical Nanotechnology
https://www.readbyqxmd.com/read/28506256/aav-vector-distribution-in-the-mouse-respiratory-tract-following-four-different-methods-of-administration
#2
Lisa A Santry, Joelle C Ingrao, Darrick L Yu, Jondavid G de Jong, Laura P van Lieshout, Geoffrey A Wood, Sarah K Wootton
BACKGROUND: Targeted delivery of gene therapy vectors to the mouse respiratory tract is often performed via intranasal or intratracheal administration; however, there can be a great deal of variability between these methods, which could potentially influence experimental results. Improving the accuracy and precision of lung delivery will not only reduce the number of animals required to detect statistically significant differences, but may reduce the variability of studies from different laboratories...
May 15, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28500326/intranasal-drug-delivery-of-small-interfering-rna-targeting-beclin1-encapsulated-with-polyethylenimine-pei-in-mouse-brain-to-achieve-hiv-attenuation
#3
Myosotys Rodriguez, Jessica Lapierre, Chet Raj Ojha, Ajeet Kaushik, Elena Batrakova, Fatah Kashanchi, Seth M Dever, Madhavan Nair, Nazira El-Hage
We previously reported that activation of the host autophagic protein, Beclin1, by HIV-1 infection represents an essential mechanism in controlling HIV replication and viral-induced inflammatory responses in microglial cells. Existing antiretroviral therapeutic approaches have been limited in their ability to cross the blood-brain barrier effectively and recognize and selectively eliminate persistent HIV-infected brain reservoirs. In the present study and for the first time, the bio-distribution and efficacy of noninvasive intranasal delivery of small interfering RNA (siRNA) against the Beclin1 gene using the cationic linear polyethylenimines (PEI) as a gene carrier was investigated in adult mouse brain...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28499841/effect-of-administration-method-animal-weight-and-age-on-the-intranasal-delivery-of-drugs-to-the-brain
#4
Jishnu K S Krishnan, Peethambaran Arun, Bhadra Chembukave, Abhilash P Appu, Nivetha Vijayakumar, John R Moffett, Narayanan Puthillathu, Aryan M A Namboodiri
BACKGROUND: The intranasal route of administration has proven to be an effective method for bypassing the blood brain barrier and avoiding first pass hepatic metabolism when targeting drugs to the brain. Most small molecules gain rapid access to CNS parenchyma when administered intranasally. However, bioavailability is affected by various factors ranging from the molecular weight of the drug to the mode of intranasal delivery. COMPARISON WITH EXISTING METHODS: We examined the effects of animal posture, intranasal application method and animal weight and age on the delivery of radiolabeled pralidoxime ((3)H-2-PAM) to the brain of rats...
May 9, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28497569/early-onset-of-efficacy-and-consistency-of-response-across-multiple-migraine-attacks-from-the-randomized-compass-study-avp-825-breath-powered-%C3%A2-exhalation-delivery-system-sumatriptan-nasal-powder-vs-oral-sumatriptan
#5
Stephen Silberstein, Paul K Winner, Peter J McAllister, Stewart J Tepper, Rashmi Halker, Ramy A Mahmoud, Joao Siffert
OBJECTIVE: To further characterize the clinical utility of AVP-825 based on additional prespecified outcomes and post hoc analyses of COMPASS, a Phase 3 comparative efficacy trial of AVP-825 vs 100 mg oral sumatriptan (NCT01667679). AVP-825 was approved in January 2016 by the US Food and Drug Administration under the name ONZETRA(®) Xsail(®) (sumatriptan nasal powder) for the acute treatment of migraine with or without aura in adults. BACKGROUND: AVP-825 is a delivery system that uses a patient's own breath to deliver low-dose sumatriptan powder to the upper posterior regions of the nasal cavity beyond the narrow nasal valve, areas lined with vascular mucosa conducive to rapid drug absorption into the systemic circulation...
May 11, 2017: Headache
https://www.readbyqxmd.com/read/28476614/a-strategy-for-bypassing-the-blood-brain-barrier-facial-intradermal-brain-targeted-delivery-via-the-trigeminal-nerve
#6
Xi-Chong Yu, Jing-Jing Yang, Bing-Hui Jin, He-Lin Xu, Hong-Yu Zhang, Jian Xiao, Cui-Tao Lu, Ying-Zheng Zhao, Wei Yang
Although intranasal delivery bypasses the blood-brain barrier (BBB), the anatomical location of the olfactory mucosa and respiratory airflow interference lead to less brain-targeted drug delivery. In addition to intranasal delivery, evidence indicates that facial intradermal injection might be a novel strategy for bypassing the BBB via the trigeminal nerve (TN). The hypothesis was verified by pharmacokinetic evaluation, nasal injury, lymphatic vessels inhibition and immunohistochemistry. Intradermal injection into the rat mystacial pad (i...
May 2, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28469551/npy1-receptor-agonist-modulates-development-of-depressive-like-behavior-and-gene-expression-in-hypothalamus-in-sps-rodent-ptsd-model
#7
Lidia Serova, Hannah Mulhall, Esther Sabban
Delivery of neuropeptide Y (NPY) to the brain by intranasal infusion soon after traumatic stress has shown therapeutic potential, and prevented development of many behavioral and neuroendocrine impairments in the single prolonged stress (SPS) animal model of PTSD. Therefore, we examined whether the Y1R preferring agonist [Leu(31)Pro(34)]NPY is sufficient to prevent development of SPS induced depressive-like behavioral changes, and hypothalamic gene expression as obtained with intranasal NPY intervention. Male Sprague-Dawely rats were given intranasal infusion of either NPY (150 μg/rat), a low (68 μg /rat), or high (132 μg/rat) dose of [Leu(31)Pro(34)]NPY or vehicle immediately following the last SPS stressor, left undisturbed for 1 week and then tested for depressive-like behavior together with naïve unstressed controls...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28467432/lactobacillus-plantarum-producing-a-chlamydia-trachomatis-antigen-induces-a-specific-iga-response-after-mucosal-booster-immunization
#8
Katarzyna Kuczkowska, Ine Myrbråten, Lise Øverland, Vincent G H Eijsink, Frank Follmann, Geir Mathiesen, Jes Dietrich
Mucosal immunity is important for the protection against a wide variety of pathogens. Traditional vaccines administered via parenteral routes induce strong systemic immunity, but they often fail to generate mucosal IgA. In contrast, bacteria-based vaccines comprise an appealing strategy for antigen delivery to mucosal sites. Vaginal infection with Chlamydia trachomatis can develop into upper genital tract infections that can lead to infertility. Therefore, the development of an effective vaccine against Chlamydia is a high priority...
2017: PloS One
https://www.readbyqxmd.com/read/28462595/intranasal-aav-mediated-gene-delivery-and-expression-of-human-iduronidase-in-the-cns-a-non-invasive-and-effective-approach-for-prevention-of-neurologic-disease-in-mucopolysaccharidosis-type-i
#9
Lalitha R Belur, Alexa Temme, Kelly M Podetz-Pedersen, Maureen Riedl, Lucy Vulchanova, Nicholas Robinson, Leah R Hanson, Karen F Kozarsky, Paul J Orchard, William H Frey Ii, Walter C Low, R Scott McIvor
Mucopolysaccharidosis type I (MPS I) is a progressive, multisystemic, inherited metabolic disease caused by deficiency of -L-iduronidase (IDUA). Current treatments for this disease are ineffective in treating CNS disease due to the inability of lysosomal enzymes to traverse the blood-brain barrier. We have taken a non-invasive and effective approach to the treatment of CNS disease by intranasal administration of an IDUA-encoding adeno-associated virus serotype 9 (AAV9) vector. Adult IDUA-deficient mice were immunotolerized at birth with human iduronidase (Aldurazyme), to prevent anti-IDUA immune response, and at 3 months of age were instilled intranasally with AAV9-IDUA vector...
May 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28450929/effect-of-intranasal-stem-cell-administration-on-the-nigrostriatal-system-in-a-mouse-model-of-parkinson-s-disease
#10
Mohamed Salama, Mahmoud Sobh, Mahmoud Emam, Ahmed Abdalla, Dina Sabry, Mohamed El-Gamal, Ahmed Lotfy, Mahmoud El-Husseiny, Mohamed Sobh, Ali Shalash, Wael My Mohamed
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28450700/sensitization-of-glioblastoma-tumor-micro-environment-to-chemo-and-immunotherapy-by-galectin-1-intranasal-knock-down-strategy
#11
Matthias Van Woensel, Thomas Mathivet, Nathalie Wauthoz, Rémi Rosière, Abhishek D Garg, Patrizia Agostinis, Véronique Mathieu, Robert Kiss, Florence Lefranc, Louis Boon, Jochen Belmans, Stefaan W Van Gool, Holger Gerhardt, Karim Amighi, Steven De Vleeschouwer
In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435493/prehospital-care-for-the-adult-and-pediatric-seizure-patient-current-evidence-based-recommendations
#12
Eric C Silverman, Karl A Sporer, Justin M Lemieux, John F Brown, Kristi L Koenig, Marianne Gausche-Hill, Eric M Rudnick, Angelo A Salvucci, Greg H Gilbert
INTRODUCTION: We sought to develop evidence-based recommendations for the prehospital evaluation and treatment of adult and pediatric patients with a seizure and to compare these recommendations against the current protocol used by the 33 emergency medical services (EMS) agencies in California. METHODS: We performed a review of the evidence in the prehospital treatment of patients with a seizure, and then compared the seizure protocols of each of the 33 EMS agencies for consistency with these recommendations...
April 2017: Western Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28430000/neuroprotective-and-regenerative-roles-of-intranasal-wnt-3a-administration-after-focal-ischemic-stroke-in-mice
#13
Zheng Zachory Wei, James Ya Zhang, Tammi M Taylor, Xiaohuan Gu, Yingying Zhao, Ling Wei
Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 µg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28416501/protocol-for-a-placebo-controlled-within-participants-crossover-trial-evaluating-the-efficacy-of-intranasal-oxytocin-to-improve-pain-and-function-among-women-with-chronic-pelvic-musculoskeletal-pain
#14
Joshua A Rash, Kirsti Toivonen, Magali Robert, Maryam Nasr-Esfahani, John F Jarrell, Tavis S Campbell
INTRODUCTION: This protocol presents the rationale and design for a trial evaluating the efficacy of intranasal oxytocin in improving pain and function among women with chronic pelvic musculoskeletal pain. Oxytocin is a neuropeptide traditionally recognised for involvement in labour, delivery and lactation. Novel evidence suggests that oxytocin decreases pain sensitivity in humans. While oxytocin administration has been reported to lower pain sensitivity among patients experiencing chronic back pain, headache, constipation and colon pain, no research has evaluated the association between intranasal oxytocin and chronic pelvic musculoskeletal pain...
April 16, 2017: BMJ Open
https://www.readbyqxmd.com/read/28400164/intranasal-and-sublingual-delivery-of-inactivated-polio-vaccine
#15
Heleen Kraan, Peter Soema, Jean-Pierre Amorij, Gideon Kersten
Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains...
May 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28386312/alleviation-of-oxidative-damage-and-involvement-of-nrf2-are-pathway-in-mesodopaminergic-system-and-hippocampus-of-status-epilepticus-rats-pretreated-by-intranasal-pentoxifylline
#16
Yunxiao Kang, Wensheng Yan, Hui Fang, Guoliang Zhang, Yakun Du, Lei Wang, Huixian Cui, Geming Shi
The current studies were aimed at evaluating the efficacy of intranasal pentoxifylline (Ptx) pretreatment in protecting mesodopaminergic system and hippocampus from oxidative damage of lithium-pilocarpine induced status epilepticus (SE) and the involvement of nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response elements pathway. Pentoxifylline was administered to rats intranasally or intraperitoneally 30 minutes before inducing SE. Our results showed the impaired visuospatial memory, the defected mesodopaminergic system, and the oxidative damage and the transient activation of Nrf2 in SE rats...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28382978/long-term-treatment-with-intranasal-insulin-ameliorates-cognitive-impairment-tau-hyperphosphorylation-and-microglial-activation-in-a-streptozotocin-induced-alzheimer-s-rat-model
#17
Zhangyu Guo, Yanxing Chen, Yan-Fang Mao, Tingting Zheng, Yasi Jiang, Yaping Yan, Xinzhen Yin, Baorong Zhang
Recent evidence reveals that aberrant brain insulin signaling plays an important role in the pathology of Alzheimer's disease (AD). Intranasal insulin administration has been reported to improve memory and attention in healthy participants and in AD patients. However, the underlying molecular mechanisms are poorly understood. Here, we treated intracerebroventricular streptozotocin-injected (ICV-STZ) rats, a commonly used animal model of sporadic AD, with daily intranasal delivery of insulin (2 U/day) for 6 consecutive weeks and then studied their cognitive function with the Morris water maze test and biochemical changes via Western blotting...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381402/transcutaneous-immunization-with-a-bandaid-prevents-experimental-otitis-media-in-a-polymicrobial-model
#18
Laura A Novotny, John D Clements, Steven D Goodman, Lauren O Bakaletz
Otitis media (OM) is a common pediatric disease and nontypeable Haemophilus influenzae (NTHI) is the predominant pathogen in chronic OM, recurrent OM and OM associated with treatment failure. OM is also a polymicrobial disease, wherein an upper respiratory tract viral infection predisposes to ascension of NTHI from the nasopharynx, the site of colonization, to the normally sterile middle ear, resulting in disease. Using a clinically relevant viral-bacterial co-infection model of NTHI-induced OM, we performed transcutaneous immunization (TCI) via a bandaid delivery system to administer each of three promising NTHI vaccine candidates derived from bacterial adhesive proteins and biofilm mediators: rsPilA, chimV4 and integration host factor...
April 5, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28372335/effects-of-regular-and-long-acting-insulin-on-cognition-and-alzheimer-s-disease-biomarkers-a-pilot-clinical-trial
#19
Suzanne Craft, Amy Claxton, Laura D Baker, Angela J Hanson, Brenna Cholerton, Emily H Trittschuh, Deborah Dahl, Erin Caulder, Bryan Neth, Thomas J Montine, Youngkyoo Jung, Joseph Maldjian, Christopher Whitlow, Seth Friedman
BACKGROUND: Long acting insulin detemir administered intranasally for three weeks enhanced memory for adults with Alzheimer's disease dementia (AD) or amnestic mild cognitive impairment (MCI). The investigation of longer-term administration is necessary to determine whether benefits persist, whether they are similar to benefits provided by regular insulin, and whether either form of insulin therapy affects AD biomarkers. OBJECTIVE: The present study aimed to determine whether four months of treatment with intranasal insulin detemir or regular insulin improves cognition, daily functioning, and AD biomarkers for adults with MCI or AD...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28364244/intranasal-delivery-of-peptide-morpholinos-to-knockdown-influenza-host-factors-in-mice
#20
Ricardo Rajsbaum
Influenza viruses replicate primarily in the lung tissue of different host species. For efficient replication the virus utilizes host factors that are expressed in target cells. Cell-penetrating peptide-conjugated Morpholino oligomers (PPMOs) designed to target viral proteins have shown promising results as potential antiviral drugs in tissue culture and animal models. However, since viruses tend to have high rates of mutations, targeting viral proteins may result in viral escape mutants. An alternative approach to inhibit virus replication with PPMOs is to target host factors that are required for virus replication...
2017: Methods in Molecular Biology
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