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.

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.

Regional susceptibilities to mitochondrial dysfunctions in the CNS

2012 ◽  
Vol 393 (4) ◽  
pp. 275-281 ◽  
Author(s):  
Milena Pinto ◽  
Alicia M. Pickrell ◽  
Carlos T. Moraes
Keyword(s):  
Mitochondrial Function ◽  
Neurological Diseases ◽  
Mitochondrial Diseases ◽  
Biochemical Properties ◽  
Specific Cell ◽  
Mitochondrial Dysfunctions ◽  
Common Features ◽  
Age Related ◽  
The Central Nervous System ◽  
The Brain

Abstract Mitochondrial dysfunctions are very common features of age-related neurological diseases such as Parkinson’s, Alzheimer’s and Huntington’s disease. Several studies have shown that bioenergetic impairments have a major role in the degeneration of the central nervous system (CNS) in these patients. Accordingly, one of the main symptoms in many mitochondrial diseases is severe encephalopathy. The heterogeneity of the brain in terms of anatomic structures, cell composition, regional functions and biochemical properties makes the analysis on this organ very complex and difficult to interpret. Humans, in addition to animal models, exposed to toxins that affect mitochondrial function, in particular oxidative phosphorylation, exhibit degeneration of specific regions within the brain. Moreover, mutations in ubiquitously expressed genes that are involved in mitochondrial function also induce regional-specific cell death in the CNS. In this review, we will discuss some current hypotheses to explain the regional susceptibilities to mitochondrial dysfunctions in the CNS.

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.

Alzheimer’s Disease Targeted Nano-Based Drug Delivery Systems

2020 ◽  
Vol 21 (7) ◽  
pp. 628-646
Author(s):  
Gülcem Altinoglu ◽  
Terin Adali
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Neurological Diseases ◽  
Sustained Drug Release ◽  
Physiochemical Properties ◽  
Conventional Drug ◽  
Health Care Burden ◽  
The Central Nervous System ◽  
Effective Drugs

Alzheimer’s disease (AD) is the most common neurodegenerative disease, and is part of a massive and growing health care burden that is destroying the cognitive function of more than 50 million individuals worldwide. Today, therapeutic options are limited to approaches with mild symptomatic benefits. The failure in developing effective drugs is attributed to, but not limited to the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. In addition, targeted drug delivery to the central nervous system (CNS), for the diagnosis and therapy of neurological diseases like AD, is restricted by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Research done over the last decade has focused on developing new strategies to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the protective barriers surrounding the CNS. Thus, nanotechnology offers new hope for AD treatment as a strong alternative to conventional drug delivery mechanisms. In this review, the potential application of nanoparticle based approaches in Alzheimer’s disease and their implications in therapy is discussed.

scholarly journals The Molecular Biology of Brain Metastasis

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Gazanfar Rahmathulla ◽  
Steven A. Toms ◽  
Robert J. Weil
Keyword(s):  
Molecular Biology ◽  
Brain Metastasis ◽  
Targeted Drug Delivery ◽  
Rapid Expansion ◽  
Genetic Mechanisms ◽  
The Central Nervous System ◽  
Targeted Drug ◽  
Underlying Mechanisms ◽  
The Brain ◽  
New Location

Metastasis to the central nervous system (CNS) remains a major cause of morbidity and mortality in patients with systemic cancers. Various crucial interactions between the brain environment and tumor cells take place during the development of the cancer at its new location. The rapid expansion in molecular biology and genetics has advanced our knowledge of the underlying mechanisms involved, from invasion to final colonization of new organ tissues. Understanding the various events occurring at each stage should enable targeted drug delivery and individualized treatments for patients, with better outcomes and fewer side effects. This paper summarizes the principal molecular and genetic mechanisms that underlie the development of brain metastasis (BrM).

scholarly journals Dynamic 3D On-Chip BBB Model Design, Development, and Applications in Neurological Diseases

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3183
Author(s):  
Xingchi Chen ◽  
Chang Liu ◽  
Laureana Muok ◽  
Changchun Zeng ◽  
Yan Li
Keyword(s):  
Targeted Delivery ◽  
Neurological Diseases ◽  
In Vitro Models ◽  
Normal Function ◽  
Human Stem Cells ◽  
Design Development ◽  
High Throughput Drug Screening ◽  
The Central Nervous System ◽  
On Chip

The blood–brain barrier (BBB) is a vital structure for maintaining homeostasis between the blood and the brain in the central nervous system (CNS). Biomolecule exchange, ion balance, nutrition delivery, and toxic molecule prevention rely on the normal function of the BBB. The dysfunction and the dysregulation of the BBB leads to the progression of neurological disorders and neurodegeneration. Therefore, in vitro BBB models can facilitate the investigation for proper therapies. As the demand increases, it is urgent to develop a more efficient and more physiologically relevant BBB model. In this review, the development of the microfluidics platform for the applications in neuroscience is summarized. This article focuses on the characterizations of in vitro BBB models derived from human stem cells and discusses the development of various types of in vitro models. The microfluidics-based system and BBB-on-chip models should provide a better platform for high-throughput drug-screening and targeted delivery.

scholarly journals Microglia: A Potential Therapeutic Target for Sepsis-Associated Encephalopathy and Sepsis-Associated Chronic Pain

2020 ◽  
Vol 11 ◽  
Author(s):  
Yi Li ◽  
Lu Yin ◽  
Zhongmin Fan ◽  
Binxiao Su ◽  
Yu Chen ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Neurological Dysfunction ◽  
Potential Therapeutic Target ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
The Relationship ◽  
The Brain

Neurological dysfunction, one of the severe manifestations of sepsis in patients, is closely related to increased mortality and long-term complications in intensive care units, including sepsis-associated encephalopathy (SAE) and chronic pain. The underlying mechanisms of these sepsis-induced neurological dysfunctions are elusive. However, it has been well established that microglia, the dominant resident immune cell in the central nervous system, play essential roles in the initiation and development of SAE and chronic pain. Microglia can be activated by inflammatory mediators, adjacent cells and neurotransmitters in the acute phase of sepsis and then induce neuronal dysfunction in the brain. With the spotlight focused on the relationship between microglia and sepsis, a deeper understanding of microglia in SAE and chronic pain can be achieved. More importantly, clarifying the mechanisms of sepsis-associated signaling pathways in microglia would shed new light on treatment strategies for SAE and chronic pain.

Current Nanoparticle Approaches in Nose to Brain Drug Delivery and Anticancer Therapy - A Review

2020 ◽  
Vol 26 (11) ◽  
pp. 1128-1137 ◽  
Author(s):  
Mohammad A. Ansari ◽  
Ill-Min Chung ◽  
Govindasamy Rajakumar ◽  
Mohammad A. Alzohairy ◽  
Mohammad N. Alomary ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Polymeric Nanoparticles ◽  
Therapeutic Agents ◽  
Vital Role ◽  
Drug Molecules ◽  
Brain Drug Delivery ◽  
Anti Cancer ◽  
The Central Nervous System ◽  
The Brain

: Nanoparticles (NPs) are unique may be organic or inorganic, play a vital role in the development of drug delivery targeting the central nervous system (CNS). Intranasal drug delivery has shown to be an efficient strategy with attractive application for drug delivery to the CNS related diseases, such as Parkinson's disease, Alzheimer 's disease and brain solid tumors. Blood brain barrier (BBB) and blood-cerebrospinal fluid barriers are natural protective hindrances for entry of drug molecules into the CNS. Nanoparticles exhibit excellent intruding capacity for therapeutic agents and overcome protective barriers. By using nanotechnology based NPs targeted, drug delivery can be improved across BBB with discharge drugs in a controlled manner. NPs confer safe from degradation phenomenon. Several kinds of NPs are used for nose to the brain (N2B) enroute, such as lipidemic nanoparticles, polymeric nanoparticles, inorganic NPs, solid lipid NPs, dendrimers. Among them, popular lipidemic and polymeric NPs are discussed, and their participation in anti-cancer activity has also been highlighted in this review.

Nose to Brain Drug Delivery System: A Comprehensive Review

2020 ◽  
Vol 10 (4) ◽  
pp. 288-299
Author(s):  
Pankaj Kumar ◽  
Varun Garg ◽  
Neeraj Mittal
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Anatomy And Physiology ◽  
Brain Drug Delivery ◽  
System A ◽  
Interesting Approach ◽  
The Central Nervous System ◽  
The Brain

Nose to brain drug delivery system is an interesting approach to deliver a drug directly in the brain through the nose. Intranasal drug delivery is very beneficial because it avoids first-pass metabolism and achieves a greater concentration of drugs in the central nervous system (CNS) at a low dose. This delivery system is used for the treatment of various neurological disorders such as Parkinson's disease, Alzheimer's disease, schizophrenia, dementia, brain cancer, etc. To treat such types of diseases, different formulations like nanoparticles (NPs), microemulsions, in situ gel, etc. can be used depending on the physiochemical properties of the drug. In this review, some essential characteristics related to the delivery of nose to the brain and their possible obstacles are underlined, which include anatomy and physiology of nose to brain delivery. This review also summarizes innovations from the past three to five years.

Nanotechnology Approaches for Enhanced CNS Drug Delivery in the Management of Schizophrenia

2021 ◽  
Author(s):  
Rajalakshmi R ◽  
Krishnakumar N Menon ◽  
Sreeja C Nair
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Symptomatic Relief ◽  
Therapeutic Strategies ◽  
Review Article ◽  
Visual Hallucinations ◽  
Cns Drug Delivery ◽  
The Central Nervous System ◽  
The Brain

Schizophrenia is a neuropsychiatric disorder mainly affecting the central nervous system, presented with auditory and visual hallucinations, delusion and withdrawal from society. Abnormal dopamine levels mainly characterise the disease; various theories of neurotransmitters explain the pathophysiology of the disease. The current therapeutic approach deals with the systemic administration of drugs other than the enteral route, altering the neurotransmitter levels within the brain and providing symptomatic relief. Fluid biomarkers help in the early detection of the disease, which would improve the therapeutic efficacy. However, the major challenge faced in CNS drug delivery is the blood-brain barrier. Nanotherapeutic approaches may overcome these limitations, which will improve safety, efficacy, and targeted drug delivery. This review article addresses the main challenges faced in CNS drug delivery and the significance of current therapeutic strategies and nanotherapeutic approaches for a better understanding and enhanced drug delivery to the brain, which improve the quality of life of schizophrenia patients.

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