The nose may help the brain: intranasal drug delivery for treating neurological diseases

2008 ◽  
Vol 3 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Weihai Ying
Keyword(s):  
Drug Delivery ◽  
Neurological Diseases ◽  
Intranasal Drug Delivery ◽  
The Brain

scholarly journals Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1929 ◽  
Author(s):  
Salman Ul Islam ◽  
Adeeb Shehzad ◽  
Muhammad Bilal Ahmed ◽  
Young Sup Lee
Keyword(s):  
Drug Delivery ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Nasal Delivery ◽  
Intranasal Route ◽  
Drug Molecules ◽  
Surface Enhanced ◽  
Effective Delivery ◽  
The Central Nervous System ◽  
The Brain

Although the global prevalence of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs’ entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices.

scholarly journals Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives

2021 ◽  
Vol 22 (12) ◽  
pp. 6442
Author(s):  
Aida Kouhi ◽  
Vyshnavi Pachipulusu ◽  
Talya Kapenstein ◽  
Peisheng Hu ◽  
Alan L. Epstein ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Neurological Diseases ◽  
High Specificity ◽  
Biochemical Properties ◽  
Antibody Engineering ◽  
Stage Of Development ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
The Brain

Due to their high specificity, monoclonal antibodies have been widely investigated for their application in drug delivery to the central nervous system (CNS) for the treatment of neurological diseases such as stroke, Alzheimer’s, and Parkinson’s disease. Research in the past few decades has revealed that one of the biggest challenges in the development of antibodies for drug delivery to the CNS is the presence of blood–brain barrier (BBB), which acts to restrict drug delivery and contributes to the limited uptake (0.1–0.2% of injected dose) of circulating antibodies into the brain. This article reviews the various methods currently used for antibody delivery to the CNS at the preclinical stage of development and the underlying mechanisms of BBB penetration. It also describes efforts to improve or modulate the physicochemical and biochemical properties of antibodies (e.g., charge, Fc receptor binding affinity, and target affinity), to adapt their pharmacokinetics (PK), and to influence their distribution and disposition into the brain. Finally, a distinction is made between approaches that seek to modify BBB permeability and those that use a physiological approach or antibody engineering to increase uptake in the CNS. Although there are currently inherent difficulties in developing safe and efficacious antibodies that will cross the BBB, the future prospects of brain-targeted delivery of antibody-based agents are believed to be excellent.

A Patent Review on Nanotechnology-Based Nose-to-Brain Drug Delivery

2020 ◽  
Vol 14 (3) ◽  
pp. 174-192 ◽  
Author(s):  
Ruchita Singh ◽  
Charles Brumlik ◽  
Mandar Vaidya ◽  
Abhishek Choudhury
Keyword(s):  
Drug Delivery ◽  
Cerebrospinal Fluid ◽  
Targeted Delivery ◽  
Delivery Systems ◽  
Performance Criteria ◽  
Drug Bioavailability ◽  
Intranasal Drug Delivery ◽  
Surface Modifiers ◽  
Brain Drug Delivery ◽  
The Brain

Background: Current cerebral drug delivery to the brain and Cerebrospinal Fluid (CSF) is limited by the Blood-Brain Barrier (BBB) or the blood-blood Cerebrospinal Fluid (CSF) barrier. The popular, non-invasive, intranasal delivery provides an exciting route for topical and systemic applications. For example, intranasal drug delivery of Central Nervous System (CNS) drugs can be designed to pass the BBB barrier via the nose-to-brain pathways. Recent nanotechnology research and patenting focus mainly on overcoming typical limitations including bioavailability, transport, BBB penetration, targeted delivery, controlled release rate and controlled degradation. Objective: The aim of the present study was to assess the state-of-the-art of nose-to-brain drug delivery systems and the role of nanotechnology in targeted delivery for the treatment of CNS and related therapeutic conditions. Methods: Patent and related searches were made with analytics to explore and organize nanotech work in intranasal drug delivery to the brain. Technical advancements were mapped by API, formulation and performance criteria. Patents and published patent applications were searched with concept tables of keywords, metadata (e.g., assignee) and patent classes (e.g., International Patent Classes and Cooperative Patent Classes). Results: The reviewed patents and published applications show a focus on formulations and therapeutic indications related to the nano-based nose-to-brain drug delivery. The main patented materials were surface modifiers, delivery systems and excipients. Conclusion: Surface modified nanoparticles can greatly improve drug transport and bioavailability of drugs, particularly higher molecular weight drugs. The most commonly used surface modifiers were chitosan, lectin and cyclodextrin-cross-linker complex. Nanoformulations of herbal drugs could increase drug bioavailability and reduce toxicity. Biotechnology-related drug delivery approaches such as monoclonal antibodies and genetically engineered proteins (molecular Trojan horses) deliver large molecule therapeutics.

scholarly journals Nanoemulsions for “Nose-to-Brain” Drug Delivery

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 84 ◽  
Author(s):  
Maria Bonferoni ◽  
Silvia Rossi ◽  
Giuseppina Sandri ◽  
Franca Ferrari ◽  
Elisabetta Gavini ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurological Diseases ◽  
High Surface ◽  
High Surface Area ◽  
Brain Targeting ◽  
Nasal Administration ◽  
Toxic Substances ◽  
Onset Of Action ◽  
Brain Drug Delivery ◽  
The Brain

The blood–brain barrier (BBB) plays a fundamental role in protecting the brain from toxic substances and therefore also controls and restricts the entry of therapeutic agents. The nasal administration of drugs using the nose-to-brain pathway allows direct drug targeting into the brain, avoiding the first-pass effect and bypassing the BBB. Through the nasal route, the drug can access the brain directly along the trigeminal and olfactory nerves, which are located in the upper part of the nasal cavity. Nanoemulsions are formulations belonging to the field of nanomedicine. They consist of emulsions (commonly oil in water) stabilized by one or more surfactants—and eventually co-surfactants—delivered in droplets of small dimensions (sizes of 100–300 nm or less) with a high surface area. A mucoadhesive polymer such as chitosan can be added to the formulation to impair rapid nasal clearance. Nanoemulsions represent promising formulations to deliver drugs directly into the brain through the intranasal route. Therefore, they can be used as a possible alternative to oral administration, avoiding problems such as low solubility in water, poor bioavailability, enzymatic degradation and slow onset of action. This review focuses the present situation in literature regarding the use of nanoemulsions for nose-to-brain targeting, with particular attention to recent publications. Nasal nanoemulsions appear to be effective, non-invasive and safe drug delivery systems to achieve brain targeting for the treatment of neurological diseases.

scholarly journals Preparation and characterisation of PHT-loaded chitosan lecithin nanoparticles for intranasal drug delivery to the brain

RSC Advances ◽  
2020 ◽  
Vol 10 (48) ◽  
pp. 28992-29009
Author(s):  
Amal Yousfan ◽  
Noelia Rubio ◽  
Abdul Hakim Natouf ◽  
Aamal Daher ◽  
Nedal Al-Kafry ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Brain Targeting ◽  
Intranasal Drug Delivery ◽  
The Brain

The use of nanoparticles (NPs) for intranasal (IN) drug delivery to the brain represents a hopeful strategy to enhance brain targeting of anti-epileptic drugs.

Mechanism of intranasal drug delivery directly to the brain

Life Sciences ◽  
2018 ◽  
Vol 195 ◽  
pp. 44-52 ◽  
Author(s):  
Tyler P. Crowe ◽  
M. Heather West Greenlee ◽  
Anumantha G. Kanthasamy ◽  
Walter H. Hsu
Keyword(s):  
Drug Delivery ◽  
Intranasal Drug Delivery ◽  
The Brain

scholarly journals Intranasal Drug Delivery: Novel Delivery Route for Management of Parkinson’s and Depression Neurological Disorders

2021 ◽  
Vol 11 (3) ◽  
pp. 3640-3651
Keyword(s):  
Drug Delivery ◽  
Neurological Disorders ◽  
Healthcare Costs ◽  
Intranasal Delivery ◽  
Intranasal Route ◽  
Intranasal Drug Delivery ◽  
Novel Approach ◽  
Delivery Route ◽  
Trigeminal Nerves ◽  
The Brain

Neurological disorders are increasing worldwide due to the rapidly aging population, which increases healthcare costs. Drug delivery to the brain is challenging because of the brain's anatomy, and orally administered drugsare mostly unable to cross BBB. Intranasal (Nose to Brain) administration of drugs is one novel approach to address this challenge. Intranasal delivery has appeared to evade the blood-brain barrier (BBB) and deliver the drug into the CNS at a higher rate and degree than another traditional route. Transport of drugs from the nasal cavity to the brain along with olfactory and trigeminal nerves. The purpose of this review is drug delivery by the intranasal route for treating neurological disorders like Parkinson’s and depression because drug delivery by other routes is unable to cross BBB. Still, delivery through the intranasal route by using the nanotechnology approach is possible to deliver the drug directly to CNS.

Blood–Brain Barrier Opening and Drug Delivery Using Focused Ultrasound and Microbubbles

2013 ◽  
pp. 148-159
Author(s):  
Elisa E. Konofagou
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Limiting Factor ◽  
Delivery Problem ◽  
Brain Drug Delivery ◽  
Blood Brain ◽  
The Brain

Current treatments of neurological and neurodegenerative diseases are limited due to the lack of a truly non-invasive, transient, and regionally selective brain drug delivery method. The brain is particularly difficult to deliver drugs to because of the blood-brain barrier (BBB). The impermeability of the BBB is due to the tight junctions connecting adjacent endothelial cells and highly regulatory transport systems of the endothelial cell membranes. The main function of the BBB is ion and volume regulation to ensure conditions necessary for proper synaptic and axonal signaling. However, the same permeability properties that keep the brain healthy also constitute the cause of the tremendous obstacles posed in its pharmacological treatment. The BBB prevents most neurologically active drugs from entering the brain and, as a result, has been isolated as the rate-limiting factor in brain drug delivery. Until a solution to the trans-BBB delivery problem is found, treatments of neurological diseases will remain impeded. Over the past decade, methods that combine Focused Ultrasound (FUS) and microbubbles have been shown to offer the unique capability of noninvasively, locally and transiently opening the BBB so as to treat central nervous system (CNS) diseases. Four of the main challenges that lie ahead are to: 1) assess its safety profile, 2) unveil the mechanism by which the BBB opens and closes, 3) control and predict the opened BBB properties and duration of the opening and 4) assess its premise in brain drug delivery. All these challenges will be discussed, findings in both small (mice) and large (non-human primates) animals will be shown and finally the case for this technique for clinical applications will be made.

scholarly journals A PERSPECTIVE REVIEW ON APPLICATIONS OF NANOPARTICLE MEDIATED DRUG DELIVERY TO THE CNS

2020 ◽  
pp. 1-4
Author(s):  
V. KEERTHANA ◽  
S. DHANALAKSHMI ◽  
N. HARIKRISHNAN
Keyword(s):  
Drug Delivery ◽  
Drug Targeting ◽  
Neurological Diseases ◽  
Semipermeable Membrane ◽  
Magic Bullet ◽  
Chemical Substances ◽  
The Central Nervous System ◽  
Brain Stroke ◽  
The Brain ◽  
Paul Ehrlich

Delivery of drugs into the brain is one of the most interesting and challenging areas of research. The blood-brain barrier (BBB) is a highly selective semipermeable membrane that separates blood from the brain in the central nervous system. It acts as a barrier to protect the brain from microbes, neurotoxins and other chemical substances and also blocks the entry of many drugs into the brain. An estimated 6.8 billion people die every year from CNS diseases like Parkinson’s disease, Alzheimer’s disease, sclerosis, brain stroke, dementia and others. According to WHO, one billion people are affected worldwide, about 50 million suffer from epilepsy and 24 million suffer from Alzheimer and other dementias. This indicates the importance of the delivery of drugs into the brain for treating various neurological diseases and psychological disorders. In drug targeting, a concept was introduced by Dr. Paul Ehrlich as a ‘magic bullet’ that gave tremendous hope for the researches to deliver drugs into the brain. This review discuses about various drug targeting strategies and applications of nanotechnology in designing drug delivery systems with the ability to cross through the BBB for treating neurological diseases.

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