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Parkinson disease and intranasal

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https://www.readbyqxmd.com/read/29779176/intranasal-delivery-of-pgdnf-dna-nanoparticles-provides-neuroprotection-in-the-rat-6-hydroxydopamine-model-of-parkinson-s-disease
#1
Amirah E-E Aly, Brendan T Harmon, Linas Padegimas, Ozge Sesenoglu-Laird, Mark J Cooper, Barbara L Waszczak
Glial cell line-derived neurotrophic factor (GDNF) gene therapy could offer a disease-modifying treatment for Parkinson's disease (PD). Here, we report that plasmid DNA nanoparticles (NPs) encoding human GDNF administered intranasally to rats induce transgene expression in the brain and protect dopamine neurons in a model of PD. To first test whether intranasal administration could transfect cells in the brain, rats were sacrificed 1 week after intranasal pGDNF NPs or the naked plasmid. GDNF ELISA revealed significant increases in GDNF expression throughout the brain for both treatments...
May 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29778792/valproic-acid-attenuates-manganese-induced-reduction-in-expression-of-glt-1-and-glast-with-concomitant-changes-in-murine-dopaminergic-neurotoxicity
#2
James Johnson, Edward Pajarillo, Pratap Karki, Judong Kim, Deok-Soo Son, Michael Aschner, Eunsook Lee
Exposure to elevated levels of manganese (Mn) causes manganism, a neurological disorder with similar characteristics to those of Parkinson's disease (PD). Valproic acid (VPA), an antiepileptic, is known to inhibit histone deacetylases and exert neuroprotective effects in many experimental models of neurological disorders. In the present study, we investigated if VPA attenuated Mn-induced dopaminergic neurotoxicity and the possible mechanisms involved in VPA's neuroprotection, focusing on modulation of astrocytic glutamate transporters (glutamate aspartate transporter, GLAST and glutamate transporter 1, GLT-1) and histone acetylation in H4 astrocyte culture and mouse models...
May 17, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29755536/preclinical-study-of-ibuprofen-loaded-transnasal-mucoadhesive-microemulsion-for-neuroprotective-effect-in-mptp-mice-model
#3
Surjyanarayan Mandal, Snigdha Das Mandal, Krishna Chuttani, Krutika K Sawant, Bharat Bhushan Subudhi
Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), showed very promising neuroprotection action, but it suffers from high first pass metabolism and limited ability to cross blood brain barrier. Severe gastric toxicity following oral administration further limits its utility. Hence, the aim of this study was to investigate whether ibuprofen loaded mucoadhesive microemulsion (MMEI) could enhance the brain uptake and could also protect the dopaminergic neurons from MPTP-mediated neural inflammation. In this work, ibuprofen loaded polycarbophil based mucoadhesive microemulsion (MMEI) was developed by using response surface methodology (RSM)...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29717617/selegiline-nanoformulation-in-attenuation-of-oxidative-stress-and-upregulation-of-dopamine-in-the-brain-for-the-treatment-of-parkinson-s-disease
#4
Shobhit Kumar, Shweta Dang, Kuldeep Nigam, Javed Ali, Sanjula Baboota
Objective of the present study was to determine whether the prepared nanoemulsion would be able to deliver selegiline to the brain by intranasal route improving its bioavailability. Antioxidant activity, pharmacokinetic parameters and dopamine concentration were determined. Oxidative stress models which had Parkinson's disease like symptoms were used to evaluate the antioxidant activity of nanoemulsion loaded with selegiline in vivo. The antioxidant activity was evaluated by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay and reducing power assay which showed high scavenging efficiency for selegiline nanoemulsion compared to pure selegiline...
May 2, 2018: Rejuvenation Research
https://www.readbyqxmd.com/read/29669501/biopharmaceutical-potential-of-selegiline-loaded-chitosan-nanoparticles-in-the-management-of-parkinson-s-disease
#5
Rajalakshmi Rukmangathen, Indira Muzib Yallamalli, Prasanna Raju Yalavarthi
Selegiline hydrochloride, a hydrophilic anti-Parkinson' moiety, undergoes extensive first-pass metabolism and has low bioavailability. A process to obtain of selegiline (SH) loaded chitosan nanoparticles was attempted to circumvent the above problem, through intranasal delivery. SH loaded polymeric nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate, and stabilized by tween 80/ poloxamer 188. The resulting nanoparticles (NPs) were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, entrapment efficiency, particle size, zeta potential and surface morphology by scanning electron microscopy...
April 18, 2018: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29614295/methodology-and-effects-of-repeated-intranasal-delivery-of-dnsp-11-in-awake-rhesus-macaques
#6
M J Stenslik, A Evans, F Pomerleau, R Weeks, P Huettl, E Foreman, J Turchan-Cholewo, A Andersen, W A Cass, Z Zhang, R C Grondin, D M Gash, G A Gerhardt, L H Bradley
BACKGROUND: To determine if the intranasal delivery of neuroactive compounds is a viable, long-term treatment strategy for progressive, chronic neurodegenerative disorders, such as Parkinson's disease (PD), intranasal methodologies in preclinical models comparable to humans are needed. NEW METHOD: We developed a methodology to evaluate the repeated intranasal delivery of neuroactive compounds on the non-human primate (NHP) brain, without the need for sedation. We evaluated the effects of the neuroactive peptide, DNSP-11 following repeated intranasal delivery and dose-escalation over the course of 10-weeks in Rhesus macaques...
March 31, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29611482/potential-use-of-nanomedicine-for-the-anti-inflammatory-treatment-of-neurodegenerative-diseases
#7
Maria Dolores Cayero-Otero, Ana M Espinosa-Oliva, Antonio J Herrera, Irene Garcia-Dominguez, Mercedes Fernandez-Arevalo, Lucia Martin-Banderas, Rocio M de Pablos
Neurodegenerative diseases, like Alzheimer´s and Parkinson´s disease, are a group of disorders that have in common their increasingly high prevalence along with the shortage of effective treatments. In addition, the scientific community faces the challenge of getting the drugs used in these treatments to cross the blood-brain barrier (BBB) and reach the brain in sufficient concentration to be able to exert its effect. Hence, researchers across multiple disciplines are working together in order to improve the ability of therapeutics to penetrate the BBB...
April 2, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29605442/intranasal-administration-of-sodium-dimethyldithiocarbamate-induces-motor-deficits-and-dopaminergic-dysfunction-in-mice
#8
Josiel M Mack, Tainara M Moura, Débora Lanznaster, Franciane Bobinski, Caio M Massari, Tuane B Sampaio, Ariana E Schmitz, Luiz F Souza, Roger Walz, Carla I Tasca, Anicleto Poli, Richard L Doty, Alcir L Dafre, Rui D Prediger
The primary etiology of Parkinson's disease (PD) remains unclear, but likely reflects a combination of genetic and environmental factors. Exposure to some pesticides, including ziram (zinc dimethyldithiocarbamate), is a relevant risk factor for PD. Like some other environmental neurotoxicants, we hypothesized that ziram can enter the central nervous system from the nasal mucosa via the olfactory nerves. To address this issue, we evaluated the effects of 1, 2 or 4 days of intranasal (i.n., 1 mg/nostril/day) infusions of sodium dimethyldithiocarbamate (NaDMDC), a dimethyldithiocarbamate more soluble than ziram, on locomotor activity in the open field, neurological severity score and rotarod performance...
March 29, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29601911/neuroprotective-effect-of-the-carnosine-%C3%AE-lipoic-acid-nanomicellar-complex-in-a-model-of-early-stage-parkinson-s-disease
#9
O I Kulikova, D S Berezhnoy, S L Stvolinsky, A V Lopachev, V S Orlova, T N Fedorova
In a model of early-stage Parkinson's disease induced by a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to Wistar rats, a neuroprotective effect of a new derivative of carnosine and α-lipoic acid (C/LA nanomicellar complex) was demonstrated. Acute intraperitoneal administration of carnosine, α-lipoic acid and C/LA complex following MPTP administration normalized the total antioxidant activity in the brain tissue. Of all the compounds tested only C/LA complex normalized the metabolism of dopamine (DA) and serotonin (5-HT), while its components did not show similar effects when used separately...
March 27, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29592535/commentary-on-some-recent-theses-relevant-to-combating-aging-april-2018
#10
Benjamin Zealley, Aubrey D N J de Grey
Theses reviewed in this issue include "An Intranasal GDNF Gene Therapy Approach for Treating Parkinson's Disease", "Controlling Depth of Cellular Quiescence By an Rb-E2F Network Switch", "Immunoregulation of the Central Response to Peripheral Nerve Injury: Motoneuron Survival and Relevance to ALS", and "Single-Cell Whole-Genome Sequencing Reveals Widespread Somatic Copy Number Variations in the Developing Cerebral Cortex".
March 28, 2018: Rejuvenation Research
https://www.readbyqxmd.com/read/29473493/current-limitations-in-the-treatment-parkinson-s-and-alzheimer-s-diseases-state-of-the-art-and-future-perspective-of-polymeric-carriers
#11
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
https://www.readbyqxmd.com/read/29391788/lactoferrin-modified-rotigotine-nanoparticles-for-enhanced-nose-to-brain-delivery-lesa-ms-ms-based-drug-biodistribution-pharmacodynamics-and-neuroprotective-effects
#12
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
https://www.readbyqxmd.com/read/29338427/lipid-nanoparticles-for-intranasal-administration-application-to-nose-to-brain-delivery
#13
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...
April 2018: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29327206/brain-photobiomodulation-therapy-a-narrative-review
#14
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/29295587/dopamine-and-levodopa-prodrugs-for-the-treatment-of-parkinson-s-disease
#15
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/29273501/selective-%C3%AE-synuclein-knockdown-in-monoamine-neurons-by-intranasal-oligonucleotide-delivery-potential-therapy-for-parkinson-s-disease
#16
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...
February 7, 2018: 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
#17
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...
April 1, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29181847/achyranthes-bidentata-polypeptide-protects-dopaminergic-neurons-from-apoptosis-in-parkinson-s-disease-models-both-in-vitro-and-in-vivo
#18
Su Peng, Caiping Wang, Jinyu Ma, Ketao Jiang, Yuhui Jiang, Xiaosong Gu, Cheng Sun
BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a neurodegenerative disorder closely associated with dopaminergic neuron loss. It is well documented that Achyranthes bidentata polypeptides (ABPP) are potent neuroprotective agents in several kinds of neurons. Therefore, we proposed that ABPP might play a beneficial role against PD by protecting dopaminergic neurons from apoptosis. EXPERIMENTAL APPROACH: SH-SY5Y cells and primary rat dopaminergic neurons were pretreated with ABPP fraction k (ABPPk), a purified fraction of ABPP, and then the cells were exposed to 1-methyl-4-phenylpyridinium iodide (MPP+ ) to induce apoptosis...
February 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29181664/immunomorphological-changes-in-the-olfactory-bulbs-of-rats-after-intranasal-administration-of-rotenone
#19
D N Voronkov, K A Kutukova, M V Ivanov, R M Khudoerkov
Changes in the structure of the olfactory bulbs after long-term intranasal administration of pesticide rotenone, a classical inductor of parkinsonism, to rats were studied by the methods of immunomorphology. In rats intranasally receiving rotenone in a dose of 2.5 mg/kg every other day over 2 weeks, a decrease in the density of dopaminergic neurons and the area of astrocyte processes in the olfactory bulbs, activation of microglia in the glomerular layer, and enhanced α-synuclein phosphorylation and its accumulation in the bodies of mitral layer neurons were observed...
December 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29164519/atorvastatin-prevents-early-oxidative-events-and-modulates-inflammatory-mediators-in-the-striatum-following-intranasal-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-administration-in-rats
#20
Naiani F Marques, Adalberto A Castro, Gianni Mancini, Fernanda L Rocha, Adair R S Santos, Rui D Prediger, Andreza Fabro De Bem, Carla I Tasca
Atorvastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor with cholesterol-lowering, anti-inflammatory, and antioxidant properties. Increasing evidence show atorvastatin acts as a protective agent against insults in the central nervous system (CNS). The regular use of statins has been associated with a reduced risk of Parkinson's disease (PD) development. Here, we evaluated early events involved in the neurotoxicity induced by intranasal (i.n.) infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rats and the potential of atorvastatin to prevent these early toxic events...
November 21, 2017: Neurotoxicity Research
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