scholarly journals Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1734
Author(s):  
Marie J. Pauwels ◽  
Charysse Vandendriessche ◽  
Roosmarijn E. Vandenbroucke
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Transport Mechanisms ◽  
Cell Type ◽  
Administration Routes ◽  
Brain Drug Delivery ◽  
Tissue Targeting ◽  
Delivery Platform ◽  
The Brain ◽  
Cns Targeting

The treatment of central nervous system (CNS) pathologies is severely hampered by the presence of tightly regulated CNS barriers that restrict drug delivery to the brain. An increasing amount of data suggests that extracellular vesicles (EVs), i.e., membrane derived vesicles that inherently protect and transfer biological cargoes between cells, naturally cross the CNS barriers. Moreover, EVs can be engineered with targeting ligands to obtain enriched tissue targeting and delivery capacities. In this review, we provide a detailed overview of the literature describing a natural and engineered CNS targeting and therapeutic efficiency of different cell type derived EVs. Hereby, we specifically focus on peripheral administration routes in a broad range of CNS diseases. Furthermore, we underline the potential of research aimed at elucidating the vesicular transport mechanisms across the different CNS barriers. Finally, we elaborate on the practical considerations towards the application of EVs as a brain drug delivery system.

Brain Drug Delivery: Overcoming the Blood-brain Barrier to Treat Tauopathies

2020 ◽  
Vol 26 (13) ◽  
pp. 1448-1465 ◽  
Author(s):  
Jozef Hanes ◽  
Eva Dobakova ◽  
Petra Majerova
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Neurodegenerative Disorders ◽  
Brain Barrier ◽  
Neuronal Function ◽  
Brain Drug Delivery ◽  
Naturally Occurring ◽  
Blood Brain ◽  
Traditional Approaches ◽  
The Brain

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.

Polymeric Nanoparticles for Brain Drug Delivery - A Review

2020 ◽  
Vol 21 (9) ◽  
pp. 649-660
Author(s):  
Subashini Raman ◽  
Syed Mahmood ◽  
Ayah R. Hilles ◽  
Md Noushad Javed ◽  
Motia Azmana ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Surface Modification ◽  
Polymeric Nanoparticles ◽  
Drug Loading ◽  
Preparation Methods ◽  
Brain Drug Delivery ◽  
Polymeric Nanoparticle ◽  
Relationship Of ◽  
The Relationship ◽  
The Brain

Background: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery. Methods: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs. Results: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain. Conclusion: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.

scholarly journals Extracellular vesicles as a next-generation drug delivery platform

2021 ◽  
Author(s):  
Inge Katrin Herrmann ◽  
Matthew John Andrew Wood ◽  
Gregor Fuhrmann
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Next Generation ◽  
Delivery Platform

scholarly journals Shortcut Approaches to Substance Delivery into the Brain Based on Intranasal Administration Using Nanodelivery Strategies for Insulin

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5188
Author(s):  
Toshihiko Tashima
Keyword(s):  
Drug Delivery ◽  
Olfactory Epithelium ◽  
Olfactory Nerve ◽  
Brain Drug Delivery ◽  
Cns Drug Delivery ◽  
Capillary Endothelial Cells ◽  
Alternative Approaches ◽  
Cns Drugs ◽  
Direct Delivery ◽  
The Brain

The direct delivery of central nervous system (CNS) drugs into the brain after administration is an ideal concept due to its effectiveness and non-toxicity. However, the blood–brain barrier (BBB) prevents drugs from penetrating the capillary endothelial cells, blocking their entry into the brain. Thus, alternative approaches must be developed. The nasal cavity directly leads from the olfactory epithelium to the brain through the cribriform plate of the skull bone. Nose-to-brain drug delivery could solve the BBB-related repulsion problem. Recently, it has been revealed that insulin improved Alzheimer’s disease (AD)-related dementia. Several ongoing AD clinical trials investigate the use of intranasal insulin delivery. Related to the real trajectory, intranasal labeled-insulins demonstrated distribution into the brain not only along the olfactory nerve but also the trigeminal nerve. Nonetheless, intranasally administered insulin was delivered into the brain. Therefore, insulin conjugates with covalent or non-covalent cargos, such as AD or other CNS drugs, could potentially contribute to a promising strategy to cure CNS-related diseases. In this review, I will introduce the CNS drug delivery approach into the brain using nanodelivery strategies for insulin through transcellular routes based on receptor-mediated transcytosis or through paracellular routes based on escaping the tight junction at the olfactory epithelium.

scholarly journals Understanding Drug Delivery to the Brain Using Liposome-Based Strategies: Studies that Provide Mechanistic Insights Are Essential

2021 ◽  
Vol 23 (6) ◽  
Author(s):  
Firda Juhairiyah ◽  
Elizabeth C. M. de Lange
Keyword(s):  
Drug Delivery ◽  
Drug Transport ◽  
Animal Studies ◽  
Time Course ◽  
Liposomal Formulation ◽  
Liposomal Drug ◽  
Brain Drug Delivery ◽  
Liposomal Formulations ◽  
The Impact ◽  
The Brain

AbstractBrain drug delivery may be restricted by the blood-brain barrier (BBB), and enhancement by liposome-based drug delivery strategies has been investigated. As access to the human brain is limited, many studies have been performed in experimental animals. Whereas providing interesting data, such studies have room for improvement to provide mechanistic insight into the rate and extent of specifically BBB transport and intrabrain distribution processes that all together govern CNS target delivery of the free drug. This review shortly summarizes BBB transport and current liposome-based strategies to overcome BBB transport restrictions, with the emphasis on how to determine the individual mechanisms that all together determine the time course of free drug brain concentrations, following their administration as such, and in liposomes. Animal studies using microdialysis providing time course information on unbound drug in plasma and brain are highlighted, as these provide the mechanistic information needed to understand BBB drug transport of the drug, and the impact of a liposomal formulations of that drug on BBB transport. Overall, these studies show that brain distribution of a drug administered as liposomal formulation depends on both drug properties and liposomal formulation characteristics. In general, evidence suggests that active transporters at the BBB, either being influx or efflux transporters, are circumvented by liposomes. It is concluded that liposomal formulations may provide interesting changes in BBB transport. More mechanistic studies are needed to understand relevant mechanisms in liposomal drug delivery to the brain, providing an improved basis for its prediction in human using animal data.

scholarly journals Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Nkafu Bechem Ndemazie ◽  
Andriana Inkoom ◽  
Ellis Fualefeh Morfaw ◽  
Taylor Smith ◽  
Monica Aghimien ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cerebrovascular Diseases ◽  
Delivery Systems ◽  
Great Resistance ◽  
New Techniques ◽  
Non Invasive ◽  
Brain Drug Delivery ◽  
Health And Disease ◽  
Invasive Techniques ◽  
The Brain

Abstract Drug delivery into the brain has for long been a huge challenge as the blood–brain barrier (BBB) offers great resistance to entry of foreign substances (with drugs inclusive) into the brain. This barrier in healthy individuals is protective to the brain, disallowing noxious substances present in the blood to get to the brain while allowing for the exchange of small molecules into the brain by diffusion. However, BBB is disrupted under certain disease conditions, such as cerebrovascular diseases including acute ischemic stroke and intracerebral hemorrhage, and neurodegenerative disorders including multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and cancers. This review aims to provide a broad overview of present-day strategies for brain drug delivery, emphasizing novel delivery systems. Hopefully, this review would inspire scientists and researchers in the field of drug delivery across BBB to uncover new techniques and strategies to optimize drug delivery to the brain. Considering the anatomy, physiology, and pathophysiological functioning of the BBB in health and disease conditions, this review is focused on the controversies drawn from conclusions of recently published studies on issues such as the penetrability of nanoparticles into the brain, and whether active targeted drug delivery into the brain could be achieved with the use of nanoparticles. We also extended the review to cover novel non-nanoparticle strategies such as using viral and peptide vectors and other non-invasive techniques to enhance brain uptake of drugs. Graphical abstract

scholarly journals Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1006 ◽  
Author(s):  
Bart de Jong ◽  
Eric Raul Barros ◽  
Joost G. J. Hoenderop ◽  
Juan Pablo Rigalli
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Early Stage ◽  
Treatment Options ◽  
Cell Types ◽  
Administration Routes ◽  
The Individual ◽  
Key Steps

Extracellular vesicles (EVs) are membrane-bilayered nanoparticles released by most cell types. Recently, an enormous number of studies have been published on the potential of EVs as carriers of therapeutic agents. In contrast to systems such as liposomes, EVs exhibit less immunogenicity and higher engineering potential. Here, we review the most relevant publications addressing the potential and use of EVs as a drug delivery system (DDS). The information is divided based on the key steps for designing an EV-mediated delivery strategy. We discuss possible sources and isolation methods of EVs. We address the administration routes that have been tested in vivo and the tissue distribution observed. We describe the current knowledge on EV clearance, a significant challenge towards enhancing bioavailability. Also, EV-engineering approaches are described as alternatives to improve tissue and cell-specificity. Finally, a summary of the ongoing clinical trials is performed. Although the application of EVs in the clinical practice is still at an early stage, a high number of studies in animals support their potential as DDS. Thus, better treatment options could be designed to precisely increase target specificity and therapeutic efficacy while reducing off-target effects and toxicity according to the individual requirements of each patient.

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.

Strategies for nose-to-brain drug delivery

2019 ◽  
Author(s):  
Rodrigo Quispe ◽  
Jorge A. Trevino ◽  
Faizan Khan ◽  
Vera Novak
Keyword(s):  
Drug Delivery ◽  
Clinical Trials ◽  
Drug Administration ◽  
Drug Uptake ◽  
Supporting Evidence ◽  
Drug Bioavailability ◽  
Brain Drug Delivery ◽  
Potential Efficacy ◽  
Intranasal Drug Administration ◽  
The Brain

"Intranasal drug administration is an effective method that has shown promise for delivering drugs directly to the brain. This approach is associated with many challenges, and efficacy in bypassing blood-brain barrier (BBB) is debated. This review describes the pathways of nose-to-brain drug delivery, physicochemical drug properties that influence drug uptake through the nasal epithelium, physiological barriers, methods to enhance nose-to-brain absorption, drug bioavailability and biodistribution, and intranasal devices for nose-to-brain drug delivery. The mechanism of each device is described and supporting evidence from clinical trials is presented. This paper summarizes strategies involved in nose-to-brain drug delivery and provides evidence of potential efficacy of nose-braindelivery from clinical trials."

Sign in / Sign up

Export Citation Format

Share Document