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https://www.readbyqxmd.com/read/28214044/enhancement-of-antigen-specific-cd4-and-cd8-t-cell-responses-using-a-self-assembled-biologic-nanolipoprotein-particle-vaccine
#1
Dina Weilhammer, Alexis D Dunkle, Craig D Blanchette, Nicholas O Fischer, Michele Corzett, Doerte Lehmann, Tyler Boone, Paul Hoeprich, Adam Driks, Amy Rasley
To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. We utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4(+) and CD8(+) T cells in vitro compared to co-administration of free OVA and MPLA...
February 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28174292/hypothalamic-and-striatal-insulin-action-suppresses-endogenous-glucose-production-and-may-stimulate-glucose-uptake-during-hyperinsulinemia-in-lean-but-not-in-overweight-men
#2
Martin Heni, Robert Wagner, Stephanie Kullmann, Sofiya Gancheva, Michael Roden, Andreas Peter, Norbert Stefan, Hubert Preissl, Hans Ulrich Häring, Andreas Fritsche
Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive.Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with D-[6,6-(2)H2]-glucose infusion to measure endogenous glucose production and glucose disappearance. On two days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an iv insulin bolus on placebo day...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28169530/intranasal-pretreatment-with-z-ligustilide-the-main-volatile-component-of-rhizoma-chuanxiong-confers-prophylaxis-against-cerebral-ischemia-via-nrf2-and-hsp70-signaling-pathways
#3
Juan Li, Jie Yu, Hui Ma, Na Yang, Li Li, Ding-Ding Zheng, Ming-Xia Wu, Zhi-Long Zhao, Hong-Yi Qi
Z-Ligustilide (Z-LIG) is a major component in Rhizoma Chuanxiong, which has been traditionally used as a health food supplement for the prevention of cerebrovascular disease in China. This study investigates the ability of intranasal Z-LIG pretreatment to enhance protection against neuronal damage in rats with middle cerebral artery occlusion (MCAO) and the role of cellular stress response mechanisms Nrf2 and HSP70. Z-LIG significantly mitigated infarct volume, neurological dysfunction, blood-brain barrier disruption, and brain edema (p < 0...
February 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28166446/use-of-intranasal-naloxone-by-basic-life-support-providers
#4
Scott G Weiner, Patricia M Mitchell, Elizabeth S Temin, Breanne K Langlois, K Sophia Dyer
STUDY OBJECTIVES: Intranasal delivery of naloxone to reverse the effects of opioid overdose by Advanced Life Support (ALS) providers has been studied in several prehospital settings. In 2006, in response to the increase in opioid-related overdoses, a special waiver from the state allowed administration of intranasal naloxone by Basic Life Support (BLS) providers in our city. This study aimed to determine: 1) if patients who received a 2-mg dose of nasal naloxone administered by BLS required repeat dosing while in the emergency department (ED), and 2) the disposition of these patients...
February 6, 2017: Prehospital Emergency Care
https://www.readbyqxmd.com/read/28161578/consensus-m2e-peptide-conjugated-to-gold-nanoparticles-confers-protection-against-h1n1-h3n2-and-h5n1-influenza-a-viruses
#5
Wenqian Tao, Brett Hurst, Akhilesh K Shakya, Md Jasim Uddin, Rohan S Ingrole, Mayra Hernandez-Sanabria, Ravi Arya, Lynn Bimler, Silke Paust, E Bart Tarbet, Harvinder Singh Gill
The extracellular domain of influenza A ion channel membrane matrix protein 2 (M2e) is considered to be a potential candidate to develop a universal influenza A vaccine. However poor immunogenicity of M2e presents a significant roadblock. We have developed a vaccine formulation comprising of the consensus M2e peptide conjugated to gold nanoparticles (AuNPs) with CpG as a soluble adjuvant (AuNP-M2e + sCpG). We demonstrate that intranasal delivery of AuNP-M2e + sCpG in mice induces lung B cell activation and robust serum anti-M2e immunoglobulin G (IgG) response, with stimulation of both IgG1 and IgG2a subtypes...
February 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28156175/docosahexaenoic-acid-mediated-targeted-and-sustained-brain-delivery-of-curcumin-microemulsion
#6
Rajshree L Shinde, Padma V Devarajan
We disclose microemulsions (ME) of curcumin (CUR) with docosahexaenoic acid (DHA)-rich oil (CUR DHA ME) for targeted delivery to the brain. MEs of CUR (5 mg/mL) with and without DHA-rich oil (CUR Capmul ME) suitable for intravenous and intranasal administration exhibited negative zeta potential, globule size  <20 nm and good stability. Following intravenous delivery MEs exhibited high brain concentration with CUR DHA ME exhibiting a 2.8-fold higher Cmax than CUR solution. Furthermore, high and sustained concentration was demonstrated even at 24 h, which was 8- and 2-fold higher than CUR solution and CUR Capmul ME, respectively...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28156162/contribution-of-both-olfactory-and-systemic-pathways-for-brain-targeting-of-nimodipine-loaded-lipo-pluronics-micelles-in-vitro-characterization-and-in-vivo-biodistribution-study-after-intranasal-and-intravenous-delivery
#7
Hassan M Rashed, Rehab N Shamma, Emad B Basalious
Nimodipine (NM) is the only FDA-approved drug for treating subarachnoid hemorrhage induced vasospasm. NM has poor oral bioavailability (5-13%) due to its low aqueous solubility, and extensive first pass metabolism. The objective of this study is to develop radiolabeled NM-loaded LPM and to test its ability prolong its circulation time, reduce its frequency of administration and eventually target it to the brain tissue. NM was radiolabeled with (99m)Tc by direct labeling method using sodium dithionite. Different reaction conditions that affect the radiolabeling yield were studied...
November 2016: Drug Delivery
https://www.readbyqxmd.com/read/28145824/intranasal-delivery-of-nanoparticle-based-vaccines
#8
Nirmal Marasini, Mariusz Skwarczynski, Istvan Toth
Most pathogens gain access to the human body and initiate systemic infections through mucosal sites. A large number of currently marketed licensed vaccines are parenterally administered; they generate strong systemic immunity but not mucosal immunity. Nasal vaccination is an appealing strategy for the induction of mucosal-specific immunity; however, its development is mostly challenged by several factors, such as inefficient antigen uptake, its rapid mucociliary clearance, size-restricted permeation across epithelial barriers and absence of safe human mucosal adjuvants...
January 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28143493/the-yin-yan-of-ccl2-a-minor-role-in-neutrophil-anti-tumor-activity-in-vitro-but-a-major-role-on-the-outgrowth-of-metastatic-breast-cancer-lesions-in-the-lung-in-vivo
#9
Nicole Lavender, Jinming Yang, Sheau-Chiann Chen, Jiqing Sai, C Andrew Johnson, Philip Owens, Gregory D Ayers, Ann Richmond
BACKGROUND: The role of the chemokine CCL2 in breast cancer is controversial. While CCL2 recruits and activates pro-tumor macrophages, it is also reported to enhance neutrophil-mediated anti-tumor activity. Moreover, loss of CCL2 in early development enhances breast cancer progression. METHODS: To clarify these conflicting findings, we examined the ability of CCL2 to alter naïve and tumor entrained neutrophil production of ROS, release of granzyme-B, and killing of tumor cells in multiple mouse models of breast cancer...
January 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28141955/investigational-new-drugs-for-allergic-rhinitis
#10
Peter A Ricketti, Sultan Alandijani, Chen Hsing Lin, Thomas B Casale
Allergic rhinitis (AR) is a multifactorial disease characterized by paroxysmal symptoms of sneezing, rhinorrhea, postnasal drip and nasal congestion. For over a century, subcutaneous allergen immunotherapy (SCIT) has been recognized as the most effective therapy to date that may modify the underlying disease course and provide long-term benefits for individuals refractory to pharmacotherapy. However, over the past 25 years, there has been substantial growth in developing alternative therapies to traditional SCIT...
January 31, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28139754/intranasal-delivery-of-a-novel-amnion-cell-secretome-prevents-neuronal-damage-and-preserves-function-in-a-mouse-multiple-sclerosis-model
#11
Reas S Khan, Kimberly Dine, Bailey Bauman, Michael Lorentsen, Lisa Lin, Helayna Brown, Leah R Hanson, Aleta L Svitak, Howard Wessel, Larry Brown, Kenneth S Shindler
The ability of a novel intranasally delivered amnion cell derived biologic to suppress inflammation, prevent neuronal damage and preserve neurologic function in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis was assessed. Currently, there are no existing optic nerve treatment methods for disease or trauma that result in permanent vision loss. Demyelinating optic nerve inflammation, termed optic neuritis, induces permanent visual dysfunction due to retinal ganglion cell damage in multiple sclerosis and experimental autoimmune encephalomyelitis...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137809/a-short-double-stapled-peptide-inhibits-respiratory-syncytial-virus-entry-and-spreading
#12
Vanessa Gaillard, Marie Galloux, Dominique Garcin, Jean-François Eléouët, Ronan Le Goffic, Thibaut Larcher, Marie-Anne Rameix-Welti, Abdelhak Boukadiri, Julien Héritier, Jean-Manuel Segura, Elodie Baechler, Miriam Arrell, Geneviève Mottet-Osman, Origène Nyanguile
Synthetic peptides derived from the heptad repeat (HR) of fusion (F) proteins can be used as dominant negative inhibitors to inhibit the fusion mechanism of class I viral F proteins. Here, we have performed a stapled peptide scan across the HR2 domain of the RSV F protein with the aim to identify a minimal domain capable of disrupting the formation of the post fusion six helix bundle required for viral cell entry. Constraining the peptides with a single staple was not sufficient to inhibit RSV infection. However, the insertion of double staples led to the identification of novel short stapled peptides, which display nanomolar potency in HEp-2 cells, and are exceptionally robust to proteolytic degradation...
January 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28128676/revisiting-the-role-of-sucrose-in-plga-peg-nanocarrier-for-potential-intranasal-delivery
#13
A Bonaccorso, T Musumeci, C Carbone, L Vicari, M Rosaria Lauro, G Puglisi
The efficient design of nanocarriers is a major challenge and must be correlated to the route of administration. Intranasal route is studied for local, systemic or cerebral treatments. In order to develop nanocarriers with suitable properties for intranasal delivery, to achieve brain, and to market the product, it is extremely important the simplification of the formulation in terms of raw materials. Surfactants and cryoprotectants are often added to improve structuration and/or storage of polymeric nanoparticles...
January 27, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/28127888/insulin-delivery-to-the-brain-using-intracranial-implantation-of-alginate-encapsulated-pancreatic-islets
#14
Konstantin Bloch, Alexey Vanichkin, Irit Gil-Ad, Pnina Vardi, Abraham Weizman
There is increasing evidence supporting a link between cognitive dysfunctions and impaired brain insulin signalling. Insulin therapy has previously been tested as an approach to ameliorate brain insulin resistance and deficiency in patients with various brain disorders. However, current strategies for insulin delivery to the brain may induce severe hypoglycaemia when injected peripherally or show poor uptake when delivered intranasally. Recently, we have shown that intracranial transplantation of naked pancreatic islets increased insulin content in the brain and attenuated cognitive dysfunctions without altering peripheral glucose homeostasis in rats with schizophrenia-like syndrome...
January 27, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28121974/intranasal-analgesia-and-sedation-in-pediatric-emergency-care-a-prospective-observational-study-on-the-implementation-of-an-institutional-protocol-in-a-tertiary-children-s-hospital
#15
Marcus Nemeth, Nils Jacobsen, Carsten Bantel, Melanie Fieler, Robert Sümpelmann, Christoph Eich
OBJECTIVES: Children presenting with acute traumatic pain or in need of therapeutic or diagnostic procedures require rapid and effective analgesia and/or sedation. Intranasal administration (INA) promises to be a reliable, minimally invasive delivery route. However, INA is still underused in Germany. We hence developed a protocol for acute pain therapy (APT) and urgent analgesia and/or sedation (UAS). Our aim was to evaluate the effectiveness and safety of our protocol. METHODS: We performed a prospective observational study in a tertiary children's hospital in Germany...
January 24, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28120848/nanogel-based-nasal-ghrelin-vaccine-prevents-obesity
#16
T Azegami, Y Yuki, S Sawada, M Mejima, K Ishige, K Akiyoshi, H Itoh, H Kiyono
Obesity is associated with multiple comorbidities such as cardiovascular diseases and has a huge economic impact on the health-care system. However, the treatment of obesity remains insufficient in terms of efficacy, tolerability, and safety. Here we created a nasal vaccine against obesity for the first time. To avoid the injectable administration-caused pain and skin-related adverse event, we focused on the intranasal route of antigen delivery. We developed a vaccine antigen (ghrelin-PspA (pneumococcal surface protein A)), which is a recombinant fusion protein incorporating ghrelin, a hormone that stimulates food intake and decreases energy expenditure, and PspA, a candidate of pneumococcal vaccine as a carrier protein...
January 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28117173/polyanhydride-nanovaccine-against-swine-influenza-virus-in-pigs
#17
Santosh Dhakal, Jonathan Goodman, Kathryn Bondra, Yashavanth S Lakshmanappa, Jagadish Hiremath, Duan-Liang Shyu, Kang Ouyang, Kyung-Il Kang, Steven Krakowka, Michael J Wannemuehler, Chang Won Lee, Balaji Narasimhan, Gourapura J Renukaradhya
We have recently demonstrated the effectiveness of an influenza A virus (IAV) subunit vaccine based on biodegradable polyanhydride nanoparticles delivery in mice. In the present study, we evaluated the efficacy of ∼200nm polyanhydride nanoparticles encapsulating inactivated swine influenza A virus (SwIAV) as a vaccine to induce protective immunity against a heterologous IAV challenge in pigs. Nursery pigs were vaccinated intranasally twice with inactivated SwIAV H1N2 (KAg) or polyanhydride nanoparticle-encapsulated KAg (KAg nanovaccine), and efficacy was evaluated against a heterologous zoonotic virulent SwIAV H1N1 challenge...
January 20, 2017: Vaccine
https://www.readbyqxmd.com/read/28102083/development-and-characterization-of-morin-hydrate-loaded-microemulsion-for-the-management-of-alzheimer-s-disease
#18
Dheeraj Sharma, Manpreet Singh, Punnet Kumar, Vir Vikram, Neeraj Mishra
The aim of this study is to prepare and characterize intranasal delivery of morin hydrate loaded microemulsion for the management of Alzheimer's diseases. After intranasal delivery, brain and blood drug concentrations were found to be higher for optimized morin hydrate loaded microemulsion as compared to plain morin hydrate. Significant (P < 0.05) reduction in assessed pharmacodynamic parameters was observed after intranasal administration of morin hydrate loaded microemulsion as compared to sham control group...
January 19, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28101766/crossing-the-blood-brain-barrier-recent-advances-in-drug-delivery-to-the-brain
#19
Mayur M Patel, Bhoomika M Patel
CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting...
January 18, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28094952/effect-of-an-enhanced-nose-to-brain-delivery-of-insulin-on-mild-and-progressive-memory-loss-in-the-senescence-accelerated-mouse
#20
Noriyasu Kamei, Misa Tanaka, Hayoung Choi, Nobuyuki Okada, Takamasa Ikeda, Rei Itokazu, Mariko Takeda-Morishita
Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia...
January 17, 2017: Molecular Pharmaceutics
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