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Intranasal delivery

Verònica Gálvez, Adrienne Li, Christina Huggins, Paul Glue, Donel Martin, Andrew A Somogyi, Angelo Alonzo, Anthony Rodgers, Philip B Mitchell, Colleen K Loo
BACKGROUND: Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. METHODS: This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam...
March 1, 2018: Journal of Psychopharmacology
Myosotys Rodriguez, Jessica Lapierre, Chet Raj Ojha, Ajeet Kaushik, Elena Batrakova, Fatah Kashanchi, Seth M Dever, Madhavan Nair, Nazira El-Hage
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
March 14, 2018: Scientific Reports
Xiaofeng Lai, Hu Zhao, Yong Zhang, Kai Guo, Yuqiao Xu, Suning Chen, Jian Zhang
Copper oxide nanoparticles (CuO NPs) are widely used as catalysts or semiconductors in material fields. Recent studies have suggested that CuO NPs have adverse genotoxicity and cytotoxicity effects on various cells. However, little is known about the toxicity of CuO NPs following exposure to murine lungs. The purpose of this fundamental research was to investigate whether CuO NPs could induce epithelial cell injury, pulmonary inflammation, and eventually fibrosis in C57BL/6 mice. Our studies showed that CuO NPs aggravated pulmonary inflammation in a dose-dependent manner...
March 14, 2018: Scientific Reports
João R Gomes, Inês Cabrito, Hugo R Soares, Susete Costelha, Anabela Teixeira, Angela Wittelsberger, Catelijne Stortelers, Peter Vanlandschoot, Maria J Saraiva
Transthyretin (TTR) is a transport protein of retinol and thyroxine in serum and cerebrospinal fluid (CSF), which is mainly secreted in liver and choroid plexus, and in smaller amounts in other cells throughout the body. The exact role of TTR and its specific expression in Central Nervous System (CNS) remains understudied. We investigated TTR expression and metabolism in CNS, through the intranasal and intracerebroventricular delivery of a specific anti-TTR Nanobody to the brain, unveiling Nanobody pharmacokinetics to the CNS...
March 12, 2018: Journal of Neurochemistry
Zineb Lakhrif, Alexis Moreau, Bruno Hérault, Anne Di-Tommaso, Matthieu Juste, Nathalie Moiré, Isabelle Dimier-Poisson, Marie-Noëlle Mévélec, Nicolas Aubrey
Toxoplasmosis is a major public health problem and the development of a human vaccine is of high priority. Efficient vaccination against Toxoplasma gondii requires both a mucosal and systemic Th1 immune response. Moreover, dendritic cells play a critical role in orchestrating the innate immune functions and driving specific adaptive immunity to T. gondii . In this study, we explore an original vaccination strategy that combines administration via mucosal and systemic routes of fusion proteins able to target the major T...
2018: Frontiers in Immunology
Kenny Schlosser, Mohamad Taha, Duncan J Stewart
There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV ) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A)...
2018: Theranostics
Dandan Wang, Jingcai Lu, Jinfei Yu, Hongjia Hou, Kees Leenhouts, Maarten L Van Roosmalen, Tiejun Gu, Chunlai Jiang, Wei Kong, Yongge Wu
BACKGROUND: Streptococcus pneumoniae is a major pathogen accounting for a large number of pneumococcal disease in worldwide. Due to the mucosal immune pathway induces both systemic and mucosal immune responses, the potential strategy to prevent pneumococcal disease may be to develop a mucosal vaccine. METHOD: In this study, we developed an intranasal pneumococcal protein vaccine based on a bacterium-like particle (BLP) delivery system. PspA is expressed and exposed on the surface of all pneumococcal strains, which confers the potential to induce immune responses to protect against pneumococcal infection...
March 2, 2018: Immunological Investigations
Gaurav Kumar, Pankaj Paliwal, Sumedha Mukherjee, Nishant Patnaik, Sairam Krishnamurthy, Ranjana Patnaik
The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid after intranasal administration in Charles-Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path. The chlorogenic acid is administered intravenously (IV) and intranasally (IN) at the dose of 10 mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method. The study observes that chlorogenic acid is rapidly absorbed in plasma with tmax of 1 min similar to IV route after IN administration...
February 24, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Chiara Tonda-Turo, Nicola Origlia, Clara Mattu, Alice Accorroni, Valeria Chiono
Alzheimer's and Parkinson's disease are the most common neurodegenerative diseases worldwide and their incidence is increasing due to the aging population. At the moment, the available therapies are not disease modifying and have several limitations, some of which are discussed in this review. One of the main limitations of these treatments is the low concentration that drugs reach in the central nervous system after systemic administration. Indeed, the presence of biological barriers, particularly the blood brain barrier (BBB), hinders the effective drug delivery to the brain, reducing the potential benefit coming from the administration of the medication...
February 21, 2018: Current Medicinal Chemistry
Hanmei Wei, Sisi Lai, Jiabao Wei, Lei Yang, Ning Jiang, Qing Wang, Yang Yu
The blood-brain barrier (BBB) restricts the delivery of most drugs to the brain. In our previous study, the feasibility of cyclovirobuxine D delivery to the brain by a non-invasive nasal route was evaluated. In this study, a suitable drug delivery system by way of intranasal administration was developed, which could improve brain targeting. First, a formulation of cyclovirobuxine D (CVB-D) based on chitosan nanoparticles (CS-CVB-D-NPs) was prepared by the modified ionotropic gelation method through single-factor screening experiment...
August 1, 2018: Journal of Nanoscience and Nanotechnology
Josephine Herz, Christian Köster, Barbara S Reinboth, Mark Dzietko, Wiebke Hansen, Hemmen Sabir, Cindy van Velthoven, Ivo Bendix, Ursula Felderhoff-Müser
Acute hypothermia treatment (HT) is the only clinically established intervention following neonatal hypoxic-ischemic brain injury. However, almost half of all cooled infants still die or suffer from long-lasting neurological impairments. Regenerative therapies, such as mesenchymal stem cells (MSC) appear promising as adjuvant therapy. In the present study, we hypothesized that HT combined with delayed MSC therapy results in augmented protection, improving long-term neurological outcome. Postnatal day 9 (P9) C57BL/6 mice were exposed to hypoxia-ischemia followed by 4 hours HT...
February 14, 2018: Brain, Behavior, and Immunity
Wenjing Qu, Na Li, Rui Yu, Wenbao Zuo, Tingting Fu, Wenling Fei, Yanhui Hou, Yanhua Liu, Jianhong Yang
The cationic dimethyldioctadecylammonium/trehalose 6,6,9-dibehenate (DDA/TDB) liposome is as a strong adjuvant system for vaccines, with remarkable immunostimulatory activity. The mucosal administration of vaccines is a potential strategy for inducing earlier and stronger mucosal immune responses to infectious diseases. In this study, we assessed whether the intranasal administration of cationic DDA/TDB liposomes combined with influenza antigen A (H3N2) can be used as a highly efficacious vaccine to induce mucosal and systemic antibody responses...
February 15, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Qingqing Meng, Aiping Wang, Hongchen Hua, Ying Jiang, Yiyun Wang, Hongjie Mu, Zimei Wu, Kaoxiang Sun
Background: Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer's disease (AD). Purpose: To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. Methods: HupA Lf-TMC NPs were prepared using the emulsion-solvent evaporation method and optimized using the Box-Behnken design...
2018: International Journal of Nanomedicine
Carla Yoko Tanikawa de Andrade, Isabel Yamanaka, Laís S Schlichta, Sabrina Karim Silva, Guilherme F Picheth, Luiz Felipe Caron, Juliana de Moura, Rilton Alves de Freitas, Larissa Magalhães Alvarenga
To propose a novel modeling of aflatoxin immunization and surrogate toxin conjugate from AFB1 vaccines, an immunogen based on the mimotope, (i.e. a peptide-displayed phage that mimics aflatoxins epitope without toxin hazards) was designed. The recombinant phage 3P30 was identified by phage display technology and exhibited the ability to bind, dose dependent, specifically to its cognate target - anti-AFB1 antibody. In immunization assay, the phage-displayed mimotope and its peptide chemically synthesized were able to induce specific anti-AFB1 antibodies, indicating the proof of concept for aflatoxin mimicry...
April 1, 2018: Carbohydrate Polymers
Dasun Wagachchi, Jia-Yun C Tsai, Callum Chalmers, Sam Blanchett, Jacelyn M S Loh, Thomas Proft
Peptide vaccines are an attractive strategy to engineer the induction of highly targeted immune responses and avoid potentially allergenic and/or reactogenic protein regions. However, peptides by themselves are often unstable and poorly immunogenic, necessitating the need for an adjuvant and a specialised delivery system. We have developed a novel peptide delivery platform (PilVax) that allows the presentation of a stabilised and highly amplified peptide as part of the group A streptococcus serotype M1 pilus structure (PilM1) on the surface of the non-pathogenic bacterium Lactococcus lactis...
February 7, 2018: Scientific Reports
Xiuju Yan, Lixiao Xu, Chenchen Bi, Dongyu Duan, Liuxiang Chu, Xin Yu, Zimei Wu, Aiping Wang, Kaoxiang Sun
Introduction: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson's disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. Materials and methods: The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry...
2018: International Journal of Nanomedicine
Kamal Dua, Dyandevi Mathure, Jyotsana R Madan, Kishore N Gujar, Ashok Tupsamundre, Hemant A Ranpise
Considering various merits associated with the nasal mucosa such large surface area, porous endothelial membrane, high blood flow, avoidance of first-pass metabolism, and ready accessibility leads to faster and higher drug absorption. Keeping these facts in mind, the objective of the present study was to develop Buspirone hydrochloride loaded niosomal in-situ nasal gel. Buspirone hydrochloride niosomal in-situ nasal gel was formulated, optimized and evaluated with the aim to deliver drug to the brain via intranasal route...
January 29, 2018: Pharmaceutical Nanotechnology
Satish K Mandlik, Nisharani S Ranpise, Bhabani S Mohanty, Pradip R Chaudhari
The present investigation deals with preparation and characterization of anti-migraine zolmitriptan (ZMT) nanostructured polymeric carriers for nose to brain drug targeting. The drug-loaded colloidal nanocarriers of ZMT were prepared by modified ionic gelation of cationic chitosan with anionic sodium tripolyphosphate and characterized for particle size, zeta potential, and entrapment efficiency. Further, in order to investigate nose to brain drug targeting, biodistribution, and brain kinetics studies were performed using 99mtechnetium radiolabeled nanocarriers (99mTc-ZMTNP) in Swiss albino mice...
January 29, 2018: Drug Delivery and Translational Research
Hyejin Kim, Takashi Kimoto, Satoko Sakai, Etsuhisa Takahashi, Hiroshi Kido
We reported previously that intranasal instillation of a synthetic human pulmonary surfactant with a carboxy vinyl polymer as a viscosity improver, named SF-10, shows potent adjuvanticity for humoral immunity in mice and cynomolgus monkeys. SF-10 effectively induces influenza hemagglutinin vaccine (HAv)-specific IgA in nasal and lung washes and IgG in sera with their neutralizing activities. Since CD8+ T cell-mediated protection is an important requirement for adaptive immunity, we investigated in this study the effects of SF-10 with antigen on local and systemic cell-mediated immunity...
2018: PloS One
Qianwen Wang, Chun-Ho Wong, H Y Edwin Chan, Wai-Yip Lee, Zhong Zuo
DB213 is an HIV-1 replication inhibitor targeting the Central Nervous System for the treatment of HIV-associated neurocognitive disorders. Current study aims to develop an in situ thermosensitive gelling system for intranasal delivery of DB213 facilitated by statistical Design of Experiment (DoE) to conduct a more efficient experimentation by extracting the maximum amount of information from limited experiments. In our current study, information was extracted from twenty-five experimental designs from MODDE® Software and a mathematical model was successfully developed to predict formulations to achieve desired performance as well as to analyze relationships between the amount of Pluronic F-127, Pluronic F-68, Chitosan, DB213 and the performances of in situ thermosensitive gels...
January 20, 2018: International Journal of Pharmaceutics
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