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Parkinson disease and intranasal

Hitoshi Sasajima, Sadaharu Miyazono, Tomohiro Noguchi, Makoto Kashiwayanagi
Exposure to environmental neurotoxins is suspected to be a risk factor for sporadic progressive neurodegenerative diseases. Parkinson's disease has been associated with exposure to the pesticide rotenone, a mitochondrial respiration inhibitor. We previously reported that intranasal administration of rotenone in mice induced dopaminergic (DA) neurodegeneration in the olfactory bulb (OB) and reduced olfactory functions. In the present study, we investigated the DA neurons in the brains of mice that were administered rotenone intranasally for an extended period...
2017: Biological & Pharmaceutical Bulletin
Chenchen Bi, Aiping Wang, Yongchao Chu, Sha Liu, Hongjie Mu, Wanhui Liu, Zimei Wu, Kaoxiang Sun, Youxin Li
Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box-Behnken experimental design...
2016: International Journal of Nanomedicine
Yan-Hua Li, Jing-Wen Yu, Jian-Yin Xi, Wen-Bo Yu, Jian-Chun Liu, Qing Wang, Li-Juan Song, Ling Feng, Ya-Ping Yan, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma
Bone marrow-derived neural stem cells (NSCs) are ideal cells for cellular therapy because of their therapeutic potential for repairing and regenerating damaged neurons. However, the optimization of implanted cells and the improvement of microenvironment in the central nervous system (CNS) are still two critical elements for enhancing therapeutic effect. In the current study, we observed the combined therapeutic effect of NSCs with fasudil in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model and explored the possible cellular and molecular mechanisms...
September 2, 2016: Molecular Neurobiology
Kamla Pathak, Nida Akhtar
BACKGROUND: Parkinson's disease (PD) is depicted as the most prevailed neurodegenerative disease being secondary to the alzheimer's disease. PD is featured by severe dropping of dopamine related neurons present in substantia nigra as well as cytoplasmic inclusions. A number of therapeutic agents are available to treat initial as well as later complications of PD. However, transport of neurotherapeutics into the brain has been a consistent challenge for researchers, because of the existence of blood-brain barrier (BBB)...
June 7, 2016: Current Drug Delivery
Peng-Hui Yang, Jian-Xiu Zhu, Ya-Dong Huang, Xian-Ying Zhang, Peng Lei, Ashley I Bush, Qi Xiang, Zhi-Jian Su, Qi-Hao Zhang
BACKGROUND: Basic fibroblast growth factor (bFGF) has been increasingly investigated due to its neuroprotection in neurodegenerative disorders. Because there are still no cures for any of these disorders, it is crucial to identify new therapeutic targets and screen potential drugs. The increased phosphorylation of tau at Ser396 leads to intracellular tau accumulation, which forms neurofibrillary tangles in Parkinson's disease (PD). In this study, neuroprotection by bFGF was observed, and the mechanisms related to its regulation of phosphorylated tau were investigated...
2016: Neuro-degenerative Diseases
Chandrakantsing Vijaysing Pardeshi, Veena Shailendra Belgamwar
Dextran sulfate sodium (DS) was allowed to interact ionically with ropinirole hydrochloride (ROPI HCl, an anti-Parkinsonian agent) to synthesize self-assembled ROPI-DS nanoplex. The preliminary objective behind ROPI-DS complexation was to enhance the partitioning of ROPI HCl and thereby its encapsulation into nanocarriers and to improve the nasal membrane permeability. Molecular interactions were computed using in silico molecular modeling. Nanoplex were characterized for physicochemical and partitioning behavior...
April 11, 2016: Artificial Cells, Nanomedicine, and Biotechnology
Chuang Guo, Li-Juan Hao, Zhao-Hui Yang, Rui Chai, Shuai Zhang, Yu Gu, Hui-Ling Gao, Man-Li Zhong, Tao Wang, Jia-Yi Li, Zhan-You Wang
Accumulating evidence suggests that an abnormal accumulation of iron in the substantia nigra (SN) is one of the defining characteristics of Parkinson's disease (PD). Accordingly, the potential neuroprotection of Fe chelators is widely acknowledged for the treatment of PD. Although desferrioxamine (DFO), an iron chelator widely used in clinical settings, has been reported to improve motor deficits and dopaminergic neuronal survival in animal models of PD, DFO has poor penetration to cross the blood-brain barrier and elicits side effects...
June 2016: Experimental Neurology
Javad Hami, Mehran Hosseini, Sekineh Shahi, Nassim Lotfi, Abolfazl Talebi, Mohammad Afshar
BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease resulting from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Increasing evidence demonstrated that mice treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in motor functions associated with disruption of DA neurons in SNc conceivably analogous to those observed in PD. L-arginine has been proposed as a novel neuroprotective agent that plays protective roles in several models of neuronal cellular damage...
October 7, 2015: Iranian Journal of Neurology
Danúbia Bonfanti Santos, Dirleise Colle, Eduardo Luiz Gasnhar Moreira, Mariana Appel Hort, Marcelo Godoi, Gael Le Douaron, Antonio Luiz Braga, Jamil Assreuy, Patrick Pierre Michel, Rui Daniel Prediger, Rita Raisman-Vozari, Marcelo Farina
Parkinson's disease (PD) is a neurodegenerative disorder characterized by non-motor and motor disabilities. This study investigated whether succinobucol (SUC) could mitigate nigrostriatal injury caused by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in mice. Moreover, the effects of SUC against MPTP-induced behavioral impairments and neurochemical changes were also evaluated. The quantification of tyrosine hydroxylase-positive (TH(+)) cells was also performed in primary mesencephalic cultures to evaluate the effects of SUC against 1-methyl-4-phenylpyridinium (MPP(+)) toxicity in vitro...
February 6, 2016: Molecular Neurobiology
Y Pang, S Lin, C Wright, J Shen, K Carter, A Bhatt, L-W Fan
Protection of substantia nigra (SN) dopaminergic (DA) neurons by neurotrophic factors (NTFs) is one of the promising strategies in Parkinson's disease (PD) therapy. A major clinical challenge for NTF-based therapy is that NTFs need to be delivered into the brain via invasive means, which often shows limited delivery efficiency. The nose to brain pathway is a non-invasive brain drug delivery approach developed in recent years. Of particular interest is the finding that intranasal insulin improves cognitive functions in Alzheimer's patients...
March 24, 2016: Neuroscience
Surjyanarayan Mandal, Snigdha Das Mandal, Krishna Chuttani, Krutika K Sawant, Bharat Bhushan Subudhi
BACKGROUND: The present study is to investigate the neuroprotective effect of ibuprofen by intranasal administration of mucoadhesive microemulsion (MMEI) against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). METHODS: Ibuprofen-loaded polycarbophil-based MMEI was developed by using response surface methodology (RSM). Ibuprofen with dose of 2.86 mg/kg/day was administered intranasally to male C57BL/6 mice for two consecutive weeks which were pre-treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals...
August 2016: Drug Development and Industrial Pharmacy
Aderbal S Aguiar, Samantha C Lopes, Fabrine S M Tristão, Daniel Rial, Gisele de Oliveira, Cláudio da Cunha, Rita Raisman-Vozari, Rui D Prediger
The classical motor symptoms of Parkinson’s disease (PD) are preceded by non-motor symptoms in preclinical stages, including cognition impairment. The current drug treatment for PD is palliative and does not meet the clinical challenges of the disease, such as levodopa-induced dyskinesia, non-motor symptoms, and neuroprotection. We investigated the neuroprotective and disease-modifying potential of physical exercise in a preclinical animal model of PD. C57BL/6 mice (adult males) ran on a horizontal treadmill for 6 weeks (moderate intensity, 5 times/week) and were treated intranasally with 65 mg/kg of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
January 2016: Neurotoxicity Research
Fabrine Sales Massafera Tristão, Márcio Lazzarini, Sabine Martin, Majid Amar, Walter Stühmer, Frank Kirchhoff, Lucas Araújo Caldi Gomes, Laurance Lanfumey, Rui D Prediger, Julia E Sepulveda, Elaine A Del-Bel, Rita Raisman-Vozari
Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons accompanied by an inflammatory reaction. The neuron-derived chemokine fractalkine (CX3CL1) is an exclusive ligand for the receptor CX3CR1 expressed on microglia. The CX3CL1/CX3CR1 signaling is important for sustaining microglial activity. Using a recently developed PD model, in which the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxin is delivered intranasally, we hypothesized that CX3CR1 could play a role in neurotoxicity and glial activation...
April 2016: Neurotoxicity Research
Amirah E-E Aly, Barbara L Waszczak
INTRODUCTION: Developing a disease-modifying gene therapy for Parkinson's disease (PD) has been a high priority for over a decade. However, due to the inability of large biomolecules to cross the blood-brain barrier (BBB), the only means of delivery to the brain has been intracerebral infusion. Intranasal administration offers a non-surgical means of bypassing the BBB to deliver neurotrophic factors, and the genes encoding them, directly to the brain. AREAS COVERED: This review summarizes: i) evidence demonstrating intranasal delivery to the brain of a number of biomolecules having therapeutic potential for various CNS disorders; and ii) evidence demonstrating neuroprotective efficacy of a subset of biomolecules specifically for PD...
2015: Expert Opinion on Drug Delivery
Amirah E-E Aly, Barbara L Waszczak
Developing a disease-modifying gene therapy for Parkinson's disease (PD) has been a high priority for over a decade. However, due to the inability of large biomolecules to cross the blood-brain barrier (BBB), the only means of delivery to the brain has been intracerebral infusion. Intranasal administration offers a non-surgical means of bypassing the BBB to deliver neurotrophic factors, and the genes encoding them, directly to the brain. Areas covered: This review summarizes: i) evidence demonstrating intranasal delivery to the brain of a number of biomolecules having therapeutic potential for various CNS disorders; and ii) evidence demonstrating neuroprotective efficacy of a subset of biomolecules specifically for PD...
August 12, 2015: Expert Opinion on Drug Delivery
Chen Chen, Amanda Przedpelski, William H Tepp, Sabine Pellett, Eric A Johnson, Joseph T Barbieri
UNLABELLED: Cholera toxin (CT) and the related heat-labile enterotoxins (LT) of Escherichia coli have been implicated as adjuvants in human therapies, but reactivity upon intranasal delivery dampened efforts to develop other clinical applications. However, each CT family member variant has unique biological properties that may warrant development as therapeutic platforms. In the current study, a nontoxic variant of the heat-labile enterotoxin IIa (LTIIa) was engineered to deliver heterologous, functional proteins into the cytosol of neurons...
2015: MBio
Laurie K Mischley, James B Leverenz, Richard C Lau, Nayak L Polissar, Moni B Neradilek, Ali Samii, Leanna J Standish
BACKGROUND: Depletion of reduced glutathione is associated with PD and glutathione augmentation has been proposed as a disease-modifying strategy. The aim of this study was to determine the safety and tolerability of intranasal reduced glutathione in individuals with PD. METHODS: Thirty individuals with PD were randomized to either placebo (saline), 300 mg/day, or 600 mg/day of intranasal glutathione in three divided daily doses. Follow-up visits included side effect screening of PD symptoms and cognition, blood chemistry, sinus irritation, and hyposmia...
October 2015: Movement Disorders: Official Journal of the Movement Disorder Society
T S Bender, M M Migliore, R B Campbell, S John Gatley, B L Waszczak
Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) exerts significant neuroprotective effects on substantia nigra (SN) neurons in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD). In this study we used enzyme-linked immunosorbent assay (ELISA) to determine GDNF brain levels and distribution to target regions (i.e. striatum and SN) following intranasal administration of GDNF at different time points after administration. Brain levels increased significantly within 1h following a single 50-μg dose of GDNF in a liposomal formulation, returning to baseline by 24h...
September 10, 2015: Neuroscience
Elisa Unti, Roberto Ceravolo, Ubaldo Bonuccelli
Apomorphine (APO) is a potent D1 and D2 dopamine agonist. Plasma maximal concentration is reached in 8-16 min with a plasma half-life of 34-70 min. Bioavailability is close to 100%. It has a rapid antiparkinsonian action after subcutaneous (s.c.) administration with a size effect comparable with that of levodopa. Trials of s.c., oral, sublingual, intravenous, rectal, intranasal and iontophoretic transdermal administration of APO have been attempted in Parkinson's disease (PD), each of these routes have shown some potential for clinical effectiveness but the majority of studies indicate that APO intermittent s...
2015: Expert Review of Neurotherapeutics
Chittaranjan Andrade
Intranasal drug delivery (INDD) systems offer a route to the brain that bypasses problems related to gastrointestinal absorption, first-pass metabolism, and the blood-brain barrier; onset of therapeutic action is rapid, and the inconvenience and discomfort of parenteral administration are avoided. INDD has found several applications in neuropsychiatry, such as to treat migraine, acute and chronic pain, Parkinson disease, disorders of cognition, autism, schizophrenia, social phobia, and depression. INDD has also been used to test experimental drugs, such as peptides, for neuropsychiatric indications; these drugs cannot easily be administered by other routes...
May 2015: Journal of Clinical Psychiatry
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