Intranasal nanoparticulate delivery systems for neurodegenerative disorders: a review

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Abstract

Neurodegenerative diseases are a significant cause of mortality worldwide, and the blood–brain barrier (BBB) poses a significant challenge for drug delivery. An intranasal route is a prominent approach among the various methods to bypass the BBB. There are different pathways involved in intranasal drug delivery. The drawbacks of this method include mucociliary clearance, enzymatic degradation and poor drug permeation. Novel nanoformulations and intranasal drug-delivery devices offer promising solutions to overcome these challenges. Nanoformulations include polymeric nanoparticles, lipid-based nanoparticles, microspheres, liposomes and noisomes. Additionally, intranasal devices could be utilized to enhance drug-delivery efficacy. Therefore, intranasal drug-delivery systems show potential for treating neurodegenerative diseases through trigeminal or olfactory pathways, which can significantly improve patient outcomes.

Abstract

Plain language summary

Neurodegenerative diseases cause severe illness worldwide, over a sixth of the world's population suffer from these diseases in which 10–15% of the world's population lose their life. The presence of the blood–brain barrier (BBB) is one of the major drawbacks for the treatment. There are many ways to bypass the BBB, the intranasal route was found to be prominent among all routes. The drug is transported across epithelial cells by passive diffusion. Drawbacks, adverse reactions and physicochemical properties of the drug affect drug availability in the brain. These drawbacks can be solved by using novel nano formulations and intranasal drug-delivery devices. Nano formulations deliver drugs with negligible disadvantages; several nano formulations suitable for nose-to-brain targeting include polymeric nanoparticles, lipid-based nanoparticles, microspheres, liposomes and niosomes. Delivery devices such as atomizers, nebulizers, pressurized olfactory devices metered-dose spray pumps and pressurized metered dose inhaler systems, dry powder inhalers, and powder devices have been used to deliver drugs to the brain through the intranasal route. The intranasal drug-delivery system could be a promising approach to treat neurodegenerative diseases, which could save the lives of a large patient population.

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ILAE official report: a practical clinical definition of epilepsy.

Robert S. Fisher, Carlos M Acevedo, Alexis Arzimanoglou … (2014)

Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age-dependent epilepsy syndrome but are now past the applicable age or who have remained seizure-free for the last 10 years and off antiseizure medicines for at least the last 5 years. "Resolved" is not necessarily identical to the conventional view of "remission or "cure." Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

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Astrocyte-endothelial interactions at the blood-brain barrier.

N. Abbott, Lars Rönnbäck, Elisabeth Hansson (2006)

The blood-brain barrier, which is formed by the endothelial cells that line cerebral microvessels, has an important role in maintaining a precisely regulated microenvironment for reliable neuronal signalling. At present, there is great interest in the association of brain microvessels, astrocytes and neurons to form functional 'neurovascular units', and recent studies have highlighted the importance of brain endothelial cells in this modular organization. Here, we explore specific interactions between the brain endothelium, astrocytes and neurons that may regulate blood-brain barrier function. An understanding of how these interactions are disturbed in pathological conditions could lead to the development of new protective and restorative therapies.

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Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

Cláudia Saraiva, Catarina Praça, Raquel Conceição Ferreira … (2016)

The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.