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https://www.readbyqxmd.com/read/27913162/intranasal-delivery-of-antipsychotic-drugs
#1
REVIEW
Yogesh K Katare, Justin E Piazza, Jayant Bhandari, Ritesh P Daya, Kosalan Akilan, Madeline J Simpson, Todd Hoare, Ram K Mishra
Antipsychotic drugs are used to treat psychotic disorders that afflict millions globally and cause tremendous emotional, economic and healthcare burdens. However, the potential of intranasal delivery to improve brain-specific targeting remains unrealized. In this article, we review the mechanisms and methods used for brain targeting via the intranasal (IN) route as well as the potential advantages of improving this type of delivery. We extensively review experimental studies relevant to intranasal delivery of therapeutic agents for the treatment of psychosis and mental illnesses...
November 29, 2016: Schizophrenia Research
https://www.readbyqxmd.com/read/27889394/nanotechnology-based-drug-delivery-systems-for-alzheimer-s-disease-management-technical-industrial-and-clinical-challenges
#2
REVIEW
Ming Ming Wen, Noha S El-Salamouni, Wessam M El-Refaie, Heba A Hazzah, Mai M Ali, Giovanni Tosi, Ragwa M Farid, Maria J Blanco-Prieto, Nashiru Billa, Amira S Hanafy
Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes...
November 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27885823/novel-functionalization-strategies-of-polymeric-nanoparticles-as-carriers-for-brain-medications
#3
Corinne Portioli, Michele Bovi, Donatella Benati, Marta Donini, Massimiliano Perduca, Alessandro Romeo, Stefano Dusi, Hugo L Monaco, Marina Bentivoglio
For targeted brain delivery, nanoparticles (NPs) should bypass the blood-brain barrier (BBB). Novel functionalization strategies, based on low-density lipoprotein receptor (LDLR) binding domain, have been here tested to increase the brain targeting efficacy of poly d,l-lactic-co-glycolic acid (PLGA) NPs, biodegradable and suited for biomedical applications. Custom-made PLGA NPs were functionalized with an apolipoprotein E modified peptide (pep-apoE) responsible for LDLR binding, or with lipocalin-type prostaglandin-d-synthase (L-PGDS), highly expressed in the brain...
November 5, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27884636/an-in-vitro-and-in-vivo-study-of-peptide-functionalized-nanoparticles-for-brain-targeting-the-importance-of-selective-blood-brain-barrier-uptake
#4
Gerard H Bode, Gregory Coué, Christian Freese, Karin E Pickl, Maria Sanchez-Purrà, Berta Albaiges, Salvador Borrós, Ewoud C van Winden, Leto-Aikaterini Tziveleka, Zili Sideratou, Johan F Engbersen, Smriti Singh, Krystyna Albrecht, Jürgen Groll, Martin Möller, Andy J G Pötgens, Christoph Schmitz, Eleonore Fröhlich, Christian Grandfils, Frank M Sinner, C James Kirkpatrick, Harry W M Steinbusch, Hans-Georg Frank, Ronald E Unger, Pilar Martinez-Martinez
Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo...
November 21, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27882692/current-progress-on-micrornas-based-therapeutics-in-neurodegenerative-diseases
#5
REVIEW
Patrícia Pereira, João A Queiroz, Ana Figueiras, Fani Sousa
MicroRNAs (miRNAs)-based therapy has recently emerged as a promising strategy in the treatments of neurodegenerative diseases. Thus, in this review, the most recent and important challenges and advances on the development of miRNA therapeutics for brain targeting are discussed. In particular, this review highlights current knowledge and progress in the field of manufacturing, recovery, isolation, purification, and analysis of these therapeutic oligonucleotides. Finally, the available miRNA delivery systems are reviewed and an analysis is presented in what concerns to the current challenges that have to be addressed to ensure their specificity and efficacy...
November 24, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27864744/a-generic-multi-compartmental-cns-distribution-model-structure-for-9-drugs-allows-prediction-of-human-brain-target-site-concentrations
#6
Yumi Yamamoto, Pyry A Välitalo, Dirk-Jan van den Berg, Robin Hartman, Willem van den Brink, Yin Cheong Wong, Dymphy R Huntjens, Johannes H Proost, An Vermeulen, Walter Krauwinkel, Suruchi Bakshi, Vincent Aranzana-Climent, Sandrine Marchand, Claire Dahyot-Fizelier, William Couet, Meindert Danhof, Johan G C van Hasselt, Elizabeth C M de Lange
PURPOSE: Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human brain disposition. METHODS: A mathematical model consisting of several physiological brain compartments in the rat was developed using rich concentration-time profiles from nine structurally diverse drugs in plasma, brain extracellular fluid, and two cerebrospinal fluid compartments...
November 18, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27845275/a-hybrid-sirna-delivery-complex-for-enhanced-brain-penetration-and-precise-amyloid-plaque-targeting-in-alzheimer-s-disease-mice
#7
Xiaoyao Zheng, Xiaoying Pang, Peng Yang, Xu Wan, Yue Wei, Qian Guo, Qizhi Zhang, Xinguo Jiang
: To realize the therapeutic potential of gene drugs for Alzheimer's disease (AD), non-invasive, tissue-specific and efficient delivery technologies must be developed. Here, a hybrid system for amyloid plaques targeted siRNA delivery was formed by PEGylated Poly(2-(N,Ndimethylamino) ethyl methacrylate) (PEG-PDMAEMA) conjugated with two d-peptides, a CGN for brain penetration and a QSH for β-amyloid binding. The hybrid complex CQ/siRNA, composed of 25% MPEG-PDMAEMA, 50% CGN-PEG-PDMAEMA and 25% QSH-PEG-PDMAEMA, showed negligible cytotoxicity and could protect siRNA from enzyme degradation...
November 11, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27826026/chitosan-nanoparticles-and-their-tween-80-modified-counterparts-disrupt-the-developmental-profile-of-zebrafish-embryos
#8
Zhongyue Yuan, Ying Li, Yulan Hu, Jian You, Kazuma Higashisaka, Kazuya Nagano, Yasuo Tsutsumi, Jianqing Gao
Chitosan nanoparticles (CS-NPs) and their Tween 80 modified counterparts (TmCS-NPs) are among the most commonly used brain-targeted vehicles. However, their potential developmental toxicity is poorly understood. In this study, zebrafish embryos are introduced as an in vivo platform. Both NPs showed a dose-dependent increase in developmental toxicity (decreased hatching rate, increased mortality and incidences of malformation). Neurobehavioral changes included decreased spontaneous movement in TmCS-NP treated embryos and hyperactive effect in CS-NP treated larvae...
November 5, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27767229/anionic-oligothiophenes-compete-for-binding-of-x-34-but-not-pib-to-recombinant-a%C3%AE-amyloid-fibrils-and-alzheimer-s-disease-brain-derived-a%C3%AE
#9
Marcus Bäck, Hanna Appelqvist, Harry LeVine, K Peter R Nilsson
Deposits comprised of amyloid-β (Aβ) are one of the pathological hallmarks of Alzheimer's disease (AD) and small hydrophobic ligands targeting these aggregated species are used clinically for the diagnosis of AD. Herein, we observed that anionic oligothiophenes efficiently displaced X-34, a Congo Red analogue, but not Pittsburgh compound B (PIB) from recombinant Aβ amyloid fibrils and Alzheimer's disease brain-derived Aβ. Overall, we foresee that the oligothiophene scaffold offers the possibility to develop novel high-affinity ligands for Aβ pathology only found in human AD brain, targeting a different site than PIB...
October 21, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27750011/endogenous-polysialic-acid-based-micelles-for-calmodulin-antagonist-delivery-against-vascular-dementia
#10
Xiao-Juan Wang, Yin-Ping Gao, Nan-Nan Lu, Wei-Shuo Li, Ji-Fang Xu, Xiao-Ying Ying, Gang Wu, Mei-Hua Liao, Chao Tan, Ling-Xiao Shao, Ying-Mei Lu, Chen Zhang, Kohji Fukunaga, Feng Han, Yong-Zhong Du
Clinical treatment for vascular dementia still remains a challenge mainly due to Blood-Brain Barrier (BBB). Here, a micelle based on polysialic acid (PSA) which is a hydrophilic and endogenous carbohydrate polymer, was designed to deliver calmodulin antagonist for therapy of vascular dementia. PSA was firstly chemically conjugated with octadecylamine (ODA), and the obtained PSA-ODA copolymer could self-assemble into micelle in aqueous solution with a 120.0 μg/mL critical micelle concentration. The calmodulin antagonist loaded PSA-ODA micelle, featuring sustained drug release behaviour over a period of 72 h with 3...
October 17, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27702697/application-of-rpmi-2650-as-a-cell-model-to-evaluate-solid-formulations-for-intranasal-delivery-of-drugs
#11
Vanessa S S Gonçalves, Ana A Matias, Joana Poejo, Ana T Serra, Catarina M M Duarte
During the development of intranasal drug delivery systems for local/systemic effect or brain targeting, it is necessary to assess its cytotoxicity and drug transport through nasal epithelium. In order to avoid animal experiments or the use of excised tissues, in vitro cell models, such as RPMI 2650 cells, are being preferred during recent years. Nevertheless, the deposition of solid formulations into nasal cell layers with further transepithelial transport rate of drugs has been poorly studied or reported...
October 1, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27682805/polysorbate-80-coated-polymeric-curcumin-nanoparticles-for-in-vivo-anti-depressant-activity-across-bbb-and-envisaged-biomolecular-mechanism-of-action-through-a-proposed-pharmacophore-model
#12
Mohammad Yusuf, Maria Khan, Riaz A Khan, Ibrahim Abdullah Maghrabi, Bahar Ahmed
Depression is a modern world epidemic. Its main causative factor is oxidative stress, as reported in study subjects. Natural products are yet to show significant therapeutic effects in comparison with synthetic drugs. Current study deals with the preparation of brain-targeted polysorbate-80-coated curcumin PLGA nanoparticles (PS-80-CUR-NP), and their characterisation via Spectral and optical methods. PS-80-CUR-NP were evaluated against the oxidative stress-mediated depressant (OSMD) activity via Force despair, Tail suspension tests and stress biomarker assay (SOD and catalase activity)...
October 14, 2016: Journal of Microencapsulation
https://www.readbyqxmd.com/read/27671875/camelid-single-domain-antibodies-a-versatile-tool-for-in-vivo-imaging-of-extracellular-and-intracellular-brain-targets
#13
Tengfei Li, Matthias Vandesquille, Fani Koukouli, Clémence Dudeffant, Ihsen Youssef, Pascal Lenormand, Christelle Ganneau, Uwe Maskos, Christian Czech, Fiona Grueninger, Charles Duyckaerts, Marc Dhenain, Sylvie Bay, Benoît Delatour, Pierre Lafaye
Detection of intracerebral targets with imaging probes is challenging due to the non-permissive nature of blood-brain barrier (BBB). The present work describes two novel single-domain antibodies (VHHs or nanobodies) that specifically recognize extracellular amyloid deposits and intracellular tau neurofibrillary tangles, the two core lesions of Alzheimer's disease (AD). Following intravenous administration in transgenic mouse models of AD, in vivo real-time two-photon microscopy showed gradual extravasation of the VHHs across the BBB, diffusion in the parenchyma and labeling of amyloid deposits and neurofibrillary tangles...
October 5, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27661966/brain-targeting-of-temozolomide-via-the-intranasal-route-using-lipid-based-nanoparticles-brain-pharmacokinetic-and-scintigraphic-analyses
#14
Anam Khan, Syed Sarim Imam, Mohammed Aqil, Abdul Ahad, Yasmin Sultana, Asgar Ali, Khalid Khan
The aim of the present work was to investigate the efficacy of temozolomide nanostructured lipid carriers (TMZ-NLCs) to enhance brain targeting via nasal route administration. The formulation was optimized by applying a four-factor, three-level Box-Behnken design. The developed formulations and the functional relationships between their independent and dependent variables were observed. The independent variables used in the formulation were gelucire (X1), liquid lipid/total lipid (X2), Tween 80 (X3), and sonication time (X4), and their effects were observed with regard to size (Y1), % drug release (Y2), and drug loading (Y3)...
October 3, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27648847/intranasal-brain-targeted-clonazepam-polymeric-micelles-for-immediate-control-of-status-epilepticus-in-vitro-optimization-ex-vivo-determination-of-cytotoxicity-in-vivo-biodistribution-and-pharmacodynamics-studies
#15
Samia A Nour, Nevine S Abdelmalak, Marianne J Naguib, Hassan M Rashed, Ahmed B Ibrahim
Clonazepam (CZ) is an anti-epileptic drug used mainly in status epilepticus (SE). The drug belongs to Class II according to BCS classification with very limited solubility and high permeability and it suffers from extensive first-pass metabolism. The aim of the present study was to develop CZ-loaded polymeric micelles (PM) for direct brain delivery allowing immediate control of SE. PM were prepared via thin film hydration (TFH) technique adopting a central composite face-centered design (CCFD). The seventeen developed formulae were evaluated in terms of entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro release...
November 2016: Drug Delivery
https://www.readbyqxmd.com/read/27629937/sirna-capsulated-brain-targeted-nanoparticles-specifically-knock-down-oatp2b1-in-mice-a-mechanism-for-acute-morphine-tolerance-suppression
#16
Zi-Zhao Yang, Li Li, Lu Wang, Ming-Cheng Xu, Sai An, Chen Jiang, Jing-Kai Gu, Zai-Jie Jim Wang, Lu-Shan Yu, Su Zeng
Regulating main brain-uptake transporter of morphine may restrict its tolerance generation, then modify its antinociception. In this study, more than 2 fold higher intracellular uptake concentrations for morphine and morphine-6-glucuronide (M6G) were observed in stable expression cells, HEK293-hOATP2B1 than HEK293-MOCK. Specifically, the Km value of morphine to OATP2B1 (57.58 ± 8.90 μM) is 1.4-time more than that of M6G (80.31 ± 21.75 μM); Cyclosporine A (CsA), an inhibitor of OATP2B1, can inhibit their intracellular accumulations with IC50 = 3...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27606701/in-vitro-in-vivo-evaluation-of-gamma-aminobutyric-acid-loadedn-n-dimethylacrylamide-based-pegylated-polymeric-nanoparticles-for-brain-delivery-to-treat-epilepsy
#17
Gülsel Yurtdaş Kırımlıoğlu, Yusuf Menceloğlu, Kevser Erol, Yasemin Yazan
Objectives of this study were the delivery of gamma aminobutyric acid (GABA) into the brain by means of developing brain targeted, nanosized, non-toxic and biocompatible polymeric nanoparticles, and investigating their effectiveness in epilepsy. For this purpose, GABA conjugated N,N-dimethylacrylamide-based pegylated nanoparticles were designed and characterised for particle size, zeta potential, pH, morphology, DSC, XRD, FTIR, GABA quantification and in vitro release. Formulations showed smaller particle size, cationic zeta potential characteristic, possible GABA polymeric matrix interaction and prolonged release pattern...
September 22, 2016: Journal of Microencapsulation
https://www.readbyqxmd.com/read/27605441/buttressing-a-balanced-brain-target-derived-fgf-signaling-regulates-excitatory-inhibitory-tone-and-adult-neurogenesis-within-the-maturating-hippocampal-network
#18
COMMENT
Ania Dabrowski, Hisashi Umemori
Brain development involves multiple levels of molecular coordination in forming a functional nervous system. The hippocampus is a brain area that is important for memory formation and spatial reasoning. During early postnatal development of the hippocampal circuit, Fibroblast growth factor 22 (FGF22) and FGF7 act to establish a balance of excitatory and inhibitory tone. Both FGFs are secreted from CA3 dendrites, acting on excitatory or inhibitory axon terminals formed onto CA3 dendrites, respectively. Mechanistically, FGF22 utilizes FGFR2b and FGFR1b to induce synaptic vesicle recruitment within axons of dentate granule cells (DGCs), and FGF7 utilizes FGFR2b to induce synaptic vesicle recruitment within interneuron axons...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27601183/deep-transcranial-magnetic-stimulation-dtms-beyond-depression
#19
Aron Tendler, Noam Barnea Ygael, Yiftach Roth, Abraham Zangen
Deep transcranial magnetic stimulation (dTMS) utilizes different H-coils to study and treat a variety of psychiatric and neurological conditions with identifiable brain targets. The availability of this technology is dramatically changing the practice of psychiatry and neurology as it provides a safe and effective way to treat even drug-resistant patients. However, up until now, no effort was made to summarize the different types of H-coils that are available, and the conditions for which they were tested. Areas covered: Here we assembled all peer reviewed publication that used one of the H-coils, together with illustrations of the effective field they generate within the brain...
October 2016: Expert Review of Medical Devices
https://www.readbyqxmd.com/read/27599376/ropren-%C3%A2-treatment-reverses-anxiety-like-behavior-and-monoamines-levels-in-gonadectomized-rat-model-of-alzheimer-s-disease
#20
Julia Fedotova, Vagif Soultanov, Tamara Nikitina, Victor Roschin, Natalia Ordyan, Lucian Hritcu
Previous studies indicated that reduced androgen levels may contribute to both physical and cognitive disorders in men, including Alzheimer's disease. New drug candidates for Alzheimer's disease in patients with androgen deficiency should ideally be able to act not only on multiple brain targets but also to correct impaired endocrine functions in hypogonadal men with Alzheimer's disease. Ropren(®) is one such candidate for the treatment of Alzheimer's disease in men with an imbalance of androgens. Accordingly, the aim of the current study was to examine the effects of long-term Ropren(®) administration (8...
September 3, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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