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https://www.readbyqxmd.com/read/29343085/a-lack-of-systemic-absorption-following-the-repeated-application-of-topical-quetiapine-in-healthy-adults
#1
Bryce Kayhart, Maria I Lapid, Sarah Nelson, Julie L Cunningham, Virginia H Thompson, Jonathan G Leung
In the absence of suitable oral or intravenous access for medication administration and when the intramuscular medications are undesirable, alternative routes for drug delivery may be considered. Antipsychotics administered via an inhaled, intranasal, rectal, or topical route have been described in the literature. Topically administered antipsychotics have been previously reported to produce negligible systemic absorption despite being used in clinical practice for nausea and behavioral symptoms associated with dementia...
January 1, 2018: American Journal of Hospice & Palliative Care
https://www.readbyqxmd.com/read/29338427/lipid-nanoparticles-for-intranasal-administration-application-to-nose-to-brain-delivery
#2
Luigi Battaglia, Pier Paolo Panciani, Elisabetta Muntoni, Maria Teresa Capucchio, Elena Biasibetti, Pasquale De Bonis, Silvia Mioletti, Marco Fontanella, Shankar Swaminathan
The blood brain barrier is a functional barrier allowing the entry into the brain of only essential nutrients, excluding other molecules. Its structure, although essential to keep the harmful entities out, is also a major roadblock for pharmacological treatment of brain diseases. Several alternative invasive drug delivery approaches, such as transcranial drug delivery and disruption of blood brain barrier have been explored, with limited success and several challenges. Intranasal delivery is a non-invasive methodology, which bypasses the systemic circulation, and, through the intra- and extra- neuronal pathways, provides direct brain drug delivery...
January 17, 2018: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29338251/delivery-of-oxytocin-to-the-brain-for-the-treatment-of-autism-spectrum-disorder-by-nasal-application
#3
Akiko Tanaka, Tomoyuki Furubayashi, Mari Arai, Daisuke Inoue, Shunsuke Kimura, Akiko Kiriyama, Kosuke Kusamori, Hidemasa Katsumi, Reiko Yutani, Toshiyasu Sakane, Akira Yamamoto
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 blood stream 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...
January 16, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29327206/brain-photobiomodulation-therapy-a-narrative-review
#4
REVIEW
Farzad Salehpour, Javad Mahmoudi, Farzin Kamari, Saeed Sadigh-Eteghad, Seyed Hossein Rasta, Michael R Hamblin
Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca2+ and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29324805/intranasal-vaccination-with-m2e5x-virus-like-particles-induces-humoral-and-cellular-immune-responses-conferring-cross-protection-against-heterosubtypic-influenza-viruses
#5
Young-Tae Lee, Eun-Ju Ko, Youri Lee, Ki-Hye Kim, Min-Chul Kim, Yu-Na Lee, Sang-Moo Kang
Current influenza vaccines do not provide broad cross-protection. Here, we report that intranasal vaccination with virus-like particles containing the highly conserved multiple ectodomains of matrix protein 2 (M2e5x VLP) of influenza virus induces broad cross-protection by M2-specific humoral and cellular immune responses. M2e5x VLP intranasal vaccination prevented severe weight loss, attenuated inflammatory cytokines and cellular infiltrates, and lowered viral loads, and induced germinal center phenotypic B and plasma cells...
2018: PloS One
https://www.readbyqxmd.com/read/29320887/transducing-airway-basal-cells-with-a-helper-dependent-adenoviral-vector-for-lung-gene-therapy
#6
Huibi Cao, Hong Ouyang, Hartmut Grasemann, Claire Bartlett, Kai Du, Rongqi Duan, Fushan Shi, Marvin Estrada, Kyle Seigel, Allan Coates, Herman Yeger, Christine Bear, Tanja Gonska, Theo Moraes, Jim Hu
A major challenge in developing gene-based therapies for airway diseases such as cystic fibrosis (CF) is sustaining therapeutic levels of transgene expression over time. This is largely due to airway epithelial cell turnover and the host immunogenicity to gene delivery vectors. Modern gene editing tools and delivery vehicles hold great potential for overcoming the challenge. There is currently not much known about how to deliver genes into airway stem cells, of which basal cells are the major type in human airways...
January 10, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29311081/antimicrobial-activity-of-ibuprofen-against-cystic-fibrosis-associated-gram-negative-pathogens
#7
Parth N Shah, Kimberly R Marshall-Batty, Justin A Smolen, Jasur A Tagaev, Qingquan Chen, Christopher A Rodesney, Henry H Le, Vernita D Gordon, David E Greenberg, Carolyn L Cannon
Clinical trials have demonstrated the benefits of ibuprofen therapy in cystic fibrosis (CF) patients, an effect that is currently attributed to ibuprofen's anti-inflammatory properties. Yet, a few previous reports demonstrate an antimicrobial activity of ibuprofen as well, although none investigate its direct effects on the pathogens found in the CF lung, which is the focus of this work. Determination of ibuprofen's in vitro antimicrobial activity against Pseudomonas aeruginosa and Burkholderia spp. strains through measurements of endpoint colony-forming units (CFU) and growth kinetics showed that ibuprofen reduces the growth rate and bacterial burden of tested strains in a dose-dependent fashion...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29299992/development-of-a-nasal-donepezil-loaded-microemulsion-for-treatment-of-alzheimer-s-disease-in-vitro-and-ex-vivo-characterization
#8
Lupe Carolina Espinoza, Marisol Vacacela, Beatriz Clares, Maria Luisa Garcia, Maria Jose Fabrega, Ana Cristina Calpena
BACKGROUND: Donepezil (DPZ) is widely prescribed as a specific and reversible acetylcholinesterase inhibitor for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). OBJECTIVE: Considering the therapeutic potential of DPZ and the advantages offered by the intranasal route as an alternative for drug administration, the aim of this study was the development and characterization of a DPZ microemulsion (ME) for nose-to-brain delivery. METHOD: The ME was developed by construction of pseudoternary phase diagrams and characterized by dynamic light scattering and transmission electron microscopy...
January 4, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29295587/dopamine-and-levodopa-prodrugs-for-the-treatment-of-parkinson-s-disease
#9
REVIEW
Fatma Haddad, Maryam Sawalha, Yahya Khawaja, Anas Najjar, Rafik Karaman
Background: Parkinson's disease is an aggressive and progressive neurodegenerative disorder that depletes dopamine (DA) in the central nervous system. Dopamine replacement therapy, mainly through actual dopamine and its original prodrug l-dopa (LD), faces many challenges such as poor blood brain barrier penetration and decreased response to therapy with time. Methods: The prodrugs described herein are ester, amide, dimeric amide, carrier-mediated, peptide transport-mediated, cyclic, chemical delivery systems and enzyme-models prodrugs designed and made by chemical means, and their bioavailability was studied in animals...
December 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29282995/nose-to-brain-transport-pathways-an-overview-potential-of-nanostructured-lipid-carriers-in-nose-to-brain-targeting
#10
Kousalya Selvaraj, Kuppusamy Gowthamarajan, Veera Venkata Satyanarayana Reddy Karri
Many of the therapeutics used for the treatment of brain disorders are not effective and not delivered to the brain due to the complex structure and its barriers. In recent years, many advanced approaches have emerged for the brain drug delivery. Intranasal drug delivery is one of non-invasive approach has gained interest because of direct transport of drugs circumventing the brain barriers through olfactory and trigeminal nerve pathways. Eventhough through these pathways the therapeutics have direct access to the brain, the main limitations of this approach are only limited drug absorption, and nasal permeability...
December 28, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29282567/demonstration-of-direct-nose-to-brain-transport-of-unbound-hiv-1-replication-inhibitor-db213-via-intranasal-administration-by-pharmacokinetic-modeling
#11
Qianwen Wang, Yufeng Zhang, Chun-Ho Wong, H Y Edwin Chan, Zhong Zuo
Intranasal administration could be an attractive alternative route of administration for the delivery of drugs to the central nervous system (CNS). However, there are always doubts about the direct transport of therapeutics from nasal cavity to the CNS since there are only limited studies on the understanding of direct nose-to-brain transport. Therefore, this study aimed to (1) investigate the existence of nose-to-brain transport of intranasally administered HIV-1 replication inhibitor DB213 and (2) assess the direct nose-to-brain transport of unbound HIV-1 replication inhibitor DB213 quantitatively by a pharmacokinetic approach...
December 27, 2017: AAPS Journal
https://www.readbyqxmd.com/read/29277310/mechanism-of-intranasal-drug-delivery-directly-to-the-brain
#12
REVIEW
Tyler P Crowe, M Heather West Greenlee, Anumantha G Kanthasamy, Walter H Hsu
Neurological diseases are becoming increasingly prominent worldwide due to rapidly aging populations, which greatly contributes to increasing healthcare costs. The development of neuroprotective drugs has so far proven exceptionally difficult due to the blood-brain barrier. One novel approach to address this challenge is to administer drugs intranasally to noninvasively bypass the blood-brain barrier. The intranasal route can thus transport drugs directly to the brain from the nasal cavity along the olfactory and trigeminal nerves...
December 22, 2017: Life Sciences
https://www.readbyqxmd.com/read/29273501/selective-%C3%AE-synuclein-knockdown-in-monoamine-neurons-by-intranasal-oligonucleotide-delivery-potential-therapy-for-parkinson-s-disease
#13
Diana Alarcón-Arís, Ariadna Recasens, Mireia Galofré, Iria Carballo-Carbajal, Nicolás Zacchi, Esther Ruiz-Bronchal, Rubén Pavia-Collado, Rosario Chica, Albert Ferrés-Coy, Marina Santos, Raquel Revilla, Andrés Montefeltro, Isabel Fariñas, Francesc Artigas, Miquel Vila, Analia Bortolozzi
Progressive neuronal death in brainstem nuclei and widespread accumulation of α-synuclein are neuropathological hallmarks of Parkinson's disease (PD). Reduction of α-synuclein levels is therefore a potential therapy for PD. However, because α-synuclein is essential for neuronal development and function, α-synuclein elimination would dramatically impact brain function. We previously developed conjugated small interfering RNA (siRNA) sequences that selectively target serotonin (5-HT) or norepinephrine (NE) neurons after intranasal administration...
November 29, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29247729/pramipexole-dihydrochloride-loaded-chitosan-nanoparticles-for-nose-to-brain-delivery-development-characterization-and-in-vivo-anti-parkinson-activity
#14
Ruhi Raj, Sarika Wairkar, Vinay Sridhar, Ram Gaud
In the current study, Pramipexole dihydrochloride loaded chitosan nanoparticles (P-CNs) were prepared for Parkinson's disease via nose to brain pathway by ionic gelation method. Optimized P-CNs with chitosan and sodium tripolyphosphate (6:1 v/v) exhibited particle size and entrapment efficiency of 292.5 nm ± 8.80 and 91.25% ± 0.95 respectively and its diffusion across the artificial membrane and goat nasal mucosa was found to be 93.32% ± 2.56 and 83.03% ± 3.48 correspondingly after 24 h...
December 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29247305/neurologic-disease-in-feline-immunodeficiency-virus-infection-disease-mechanisms-and-therapeutic-interventions-for-neuroaids
#15
Christopher Power
Feline immunodeficiency virus (FIV) is a lentivirus that causes immunosuppression through virus-mediated CD4+ T cell depletion in feline species. FIV infection is complicated by virus-induced disease in the nervous system. FIV enters the brain soon after primary infection and is detected as FIV-encoded RNA, DNA, and proteins in microglia, macrophages, and astrocytes. FIV infection activates neuroinflammatory pathways including cytokines, chemokines, proteases, and ROS with accompanying neuronal injury and loss...
December 15, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29243172/therapeutic-delivery-of-simvastatin-loaded-in-pla-peg-polymersomes-resulted-in-amplification-of-anti-inflammatory-effects-in-activated-microglia
#16
Dharani Manickavasagam, Kimberly Novak, Moses O Oyewumi
Simvastatin (Sim), a lipid-lowering drug has been studied in chronic neuroinflammation associated with degenerative brain disorders due to its potential protective properties against inflammatory reaction, oxidative damage, neuronal dysfunction, and death. Meanwhile, potential application of Sim in neuroinflammation will require a suitable delivery system that can overcome notable challenges pertaining to poor blood-brain barrier (BBB) permeability and side/off-target effects. Herein, we engineered and characterized nano-sized polymersomes loaded with Sim (Sim-Ps) using PEG-PdLLA (methoxy polyethylene glycol-poly(D,L) lactic acid) diblock co-polymers...
December 14, 2017: AAPS Journal
https://www.readbyqxmd.com/read/29228824/development-of-novel-bioadhesive-granisetron-hydrochloride-spanlastic-gel-and-insert-for-brain-targeting-and-study-their-effects-on-rats
#17
Rehab Abdelmonem, Mohamed El Nabarawi, Alshaimaa Attia
The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive gels and lyophilized inserts for intranasal administration to improve GH bioavailability and brain targeting. Carpapol 934 and HPMC were incorporated in GH spanlastic in nasal gels (GHSpNGs). Gelatin and HPMC as matrix former, glycine as a collapse protecting and mannitol as an insert filler and sweeting agent were used to prepare GH spanlastic loaded in lyophilized inserts (GHSpNIs). The prepared GHSpNGs were characterized for pH measurement, drug content, rheology, and in vitro drug release...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29227037/prospective-transfrontal-sheep-model-of-skull-base-reconstruction-using-vascularized-mucosa
#18
Sarina K Mueller, George Scangas, Mansor M Amiji, Benjamin S Bleier
BACKGROUND: No high-fidelity animal model exists to examine prospective wound healing following vascularized reconstruction of the skull base. Such a model would require the ability to study the prospective behavior of vascularized mucosal repairs of large dural and arachnoid defects within the intranasal environment. The objective of this study was to therefore develop and validate a novel, in vivo, transfrontal sheep model of cranial base repair using vascularized sinonasal mucosa. METHODS: Twelve transfrontal craniotomy and 1...
December 11, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/29223454/preparation-characterization-and-immunological-evaluation-of-alginate-nanoparticles-loaded-with-whole-inactivated-influenza-virus-dry-powder-formulation-for-nasal-immunization-in-rabbits
#19
Solmaz Dehghan, Masoumeh Tavassoti Kheiri, Khalil Abnous, Maryam Eskandari, Mohsen Tafaghodi
It has become important to explore more efficient and feasible influenza vaccines, since epidemics of influenza virus cause hundreds of thousands of deaths all around the world. Improving immunogenicity of parentral influenza vaccines has given rise to mucosal delivery routes. In this study, alginate nanoparticles (NPs) were efficiently synthetized by ionic gelation method and influenza virus and CpG ODN or Quillaja Saponin (QS) adjuvants were actively incorporated into alginate NPs. The prepared particles were evaluated for both humoral and cellular immune responses in rabbits' nostrils...
December 6, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29200850/enhanced-efficacy-of-sublingual-immunotherapy-by-liposome-mediated-delivery-of-allergen
#20
Have Aliu, Carola Rask, Jens Brimnes, Thomas Lars Andresen
Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development of allergen delivery systems enabling more efficient delivery and hence lower allergen load might reduce the adverse events. In the present study, we have investigated neutral and cationic liposomes as delivery systems of ovalbumin (OVA), as a model allergen, in an OVA-induced allergic airway inflammation model...
2017: International Journal of Nanomedicine
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