scholarly journals Review of Current Strategies for Delivering Alzheimer’s Disease Drugs across the Blood-Brain Barrier

2019 ◽  
Vol 20 (2) ◽  
pp. 381 ◽  
Author(s):  
Ka Wong ◽  
Muhammad Riaz ◽  
Yuning Xie ◽  
Xue Zhang ◽  
Qiang Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Metallic Nanoparticles ◽  
Drug Delivery Systems ◽  
Current Knowledge ◽  
Delivery Systems ◽  
Brain Barrier ◽  
Blood Brain

Effective therapy for Alzheimer’s disease is a major challenge in the pharmaceutical sciences. There are six FDA approved drugs (e.g., donepezil, memantine) that show some effectiveness; however, they only relieve symptoms. Two factors hamper research. First, the cause of Alzheimer’s disease is not fully understood. Second, the blood-brain barrier restricts drug efficacy. This review summarized current knowledge relevant to both of these factors. First, we reviewed the pathophysiology of Alzheimer’s disease. Next, we reviewed the structural and biological properties of the blood-brain barrier. We then described the most promising drug delivery systems that have been developed in recent years; these include polymeric nanoparticles, liposomes, metallic nanoparticles and cyclodextrins. Overall, we aim to provide ideas and clues to design effective drug delivery systems for penetrating the blood-brain barrier to treat Alzheimer’s disease.

Recent Advances in Targeted Drug Delivery Approaches using Lipidic and Polymeric Nanocarriers for the management of Alzheimer’s Disease

2021 ◽  
Vol 27 ◽  
Author(s):  
Dhara Lakdawala ◽  
Md Abdur Rashid ◽  
Farhan Jalees Ahmad
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Targeted Drug Delivery ◽  
Brain Barrier ◽  
Polymeric Nanocarriers ◽  
Blood Brain ◽  
Targeted Drug ◽  
The Brain

: Drug delivery to the brain has remained a significant challenge in treating neurodegenerative disorders such as Alzheimer's disease due to the presence of the blood-brain barrier, which primarily obstructs the access of drugs and biomolecules into the brain. Several methods to overcome the blood-brain barrier have been employed, such as chemical disruption, surgical intervention, focused ultrasound, intranasal delivery and using nanocarriers. Nanocarrier systems remain the method of choice and have shown promising results over the past decade to achieve better drug targeting. Polymeric nanocarriers and lipidic nanoparticles act as a carrier system providing better encapsulation of drugs, site-specific delivery, increased bioavailability and sustained release of drugs. The surface modifications and functionalization of these nanocarrier systems have greatly facilitated targeted drug delivery. The safety and efficacy of these nanocarrier systems have been ascertained by several in vitro and in vivo models. In the present review, we have elaborated on recent developments of nanoparticles as a drug delivery system for Alzheimer's disease, explicitly focusing on polymeric and lipidic nanoparticles.

scholarly journals Dendrimeric Poly(Epsilon-Lysine) Delivery Systems for the Enhanced Permeability of Flurbiprofen across the Blood-Brain Barrier in Alzheimer’s Disease

2018 ◽  
Vol 19 (10) ◽  
pp. 3224 ◽  
Author(s):  
Shafq Al-azzawi ◽  
Dhafir Masheta ◽  
Anna Guildford ◽  
Gary Phillips ◽  
Matteo Santin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Solid Phase ◽  
Synthesis Method ◽  
Delivery Systems ◽  
Brain Barrier ◽  
Target Cells ◽  
Target Tissue ◽  
Blood Brain

Alzheimer’s disease (AD) is a progressive brain disorder and age-related disease characterised by abnormal accumulation of β-amyloid (Aβ). The development of drugs to combat AD is hampered by the lack of therapeutically-active molecules able to cross the blood-brain barrier (BBB). It is agreed that specifically-designed carriers, such as dendrimers, could support the drug penetration across the BBB. The aim of this study was to design biocompatible and biodegradable dendrimeric delivery systems able to carry Flurbiprofen (FP), as drug for AD treatment, across the BBB and liberate it at the target tissue. These dendrons were synthesised using solid-phase peptide synthesis method and characterised by mass spectrometry and fourier-transform infrared spectroscopy (FTIR). The results revealed successful synthesis of dendrons having FP been integrated during the synthesis at their branching ends. Cytotoxicity assays demonstrated the biocompatibility of the delivery systems, whereas HPLC analysis showed high percentages of permeability across an in vitro BBB model for FP-integrated dendrons. Results also revealed the efficiency of drug conjugates on the γ-secretase enzyme in target cells with evidence of eventual drug release by hydrolysis of the carrier. This study demonstrates that the coupling of FP to dendrimeric delivery systems can successfully be achieved during the synthesis of the poly(epsilon-lysine) macromolecules to improve the transport of the active drug across the BBB.

Efficiency of lipid-based nano drug delivery systems in crossing the blood-brain barrier: a review

2021 ◽  
pp. 118278
Author(s):  
Maliheh Dayani ◽  
Salar Khaledian ◽  
Arad Fatahian ◽  
Reza Fatahian ◽  
Fleming Martinez
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Brain Barrier ◽  
Blood Brain ◽  
Nano Drug Delivery

scholarly journals Modeling the Blood–Brain Barrier to Understand Drug Delivery in Alzheimer’s Disease

2020 ◽  
pp. 117-134
Author(s):  
Joanna M. Wasielewska ◽  
◽  
Juliana C Da Silva Chaves ◽  
Anthony R. White ◽  
Lotta E. Oikari ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Treatment of Alzheimer’s Disease and Blood–Brain Barrier Drug Delivery

2020 ◽  
Vol 13 (11) ◽  
pp. 394 ◽  
Author(s):  
William M. Pardridge
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Blood Brain Barrier ◽  
New Drugs ◽  
Brain Barrier ◽  
Biologic Drugs ◽  
Blood Brain ◽  
Delivery Technology

Despite the enormity of the societal and health burdens caused by Alzheimer’s disease (AD), there have been no FDA approvals for new therapeutics for AD since 2003. This profound lack of progress in treatment of AD is due to dual problems, both related to the blood–brain barrier (BBB). First, 98% of small molecule drugs do not cross the BBB, and ~100% of biologic drugs do not cross the BBB, so BBB drug delivery technology is needed in AD drug development. Second, the pharmaceutical industry has not developed BBB drug delivery technology, which would enable industry to invent new therapeutics for AD that actually penetrate into brain parenchyma from blood. In 2020, less than 1% of all AD drug development projects use a BBB drug delivery technology. The pathogenesis of AD involves chronic neuro-inflammation, the progressive deposition of insoluble amyloid-beta or tau aggregates, and neural degeneration. New drugs that both attack these multiple sites in AD, and that have been coupled with BBB drug delivery technology, can lead to new and effective treatments of this serious disorder.

Drug Delivery Systems and Strategies to Overcome the Barriers of Brain

2021 ◽  
Vol 28 ◽  
Author(s):  
Yogesh Garg ◽  
Deepak N Kapoor ◽  
Abhishek Kumar Sharma ◽  
Amit Bhatia
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Brain Barrier ◽  
Olfactory Pathway ◽  
Hydrophilic Drugs ◽  
Blood Brain ◽  
Effective Delivery ◽  
The Brain

Abstract: The transport of drugs to the central nervous system is the most challenging task for conventional drug delivery systems. Reduced permeability of drugs through the blood-brain barrier is a major hurdle in delivering drugs to the brain. Hence, various strategies for improving drug delivery through the blood-brain barrier are currently being explored. Novel drug delivery systems (NDDS) offer several advantages, including high chemical and biological stability, suitability for both hydrophobic and hydrophilic drugs, and can be administered through different routes. Furthermore, the conjugation of suitable ligands with these carriers tend to potentiate targeting to the endothelium of the brain and could facilitate the internalization of drugs through endocytosis. Further, the intranasal route has also shown potential, as a promising alternate route, for the delivery of drugs to the brain. This can deliver the drugs directly to the brain through the olfactory pathway. In recent years, several advancements have been made to target and overcome the barriers of the brain. This article deals with a detailed overview of the diverse strategies and delivery systems to overcome the barriers of the brain for effective delivery of drugs.

Do Periodontal Pathogens or Associated Virulence Factors Have a Deleterious Effect on the Blood-Brain Barrier, Contributing to Alzheimer’s Disease?

2021 ◽  
pp. 1-17
Author(s):  
Mhd Ammar Kouki ◽  
Anna Barlach Pritchard ◽  
Jane Elizabeth Alder ◽  
StJohn Crean
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Virulence Factors ◽  
Current Knowledge ◽  
Brain Barrier ◽  
Periodontal Pathogens ◽  
Blood Brain

The central nervous system (CNS) is protected by a highly selective barrier, the blood-brain barrier (BBB), that regulates the exchange and homeostasis of bloodborne molecules, excluding xenobiotics. This barrier forms the first line of defense by prohibiting pathogens from crossing to the CNS. Aging and chronic exposure of the BBB to pathogens renders it permeable, and this may give rise to pathology in the CNS such as Alzheimer’s disease (AD). Researchers have linked pathogens associated with periodontitis to neuroinflammation and AD-like pathology in vivo and in vitro. Although the presence of periodontitis-associated bacteria has been linked to AD in several clinical studies as DNA and virulence factors were confirmed in brain samples of human AD subjects, the mechanism by which the bacteria traverse to the brain and potentially influences neuropathology is unknown. In this review, we present current knowledge about the association between periodontitis and AD, the mechanism whereby periodontal pathogens might provoke neuroinflammation and how periodontal pathogens could affect the BBB. We suggest future studies, with emphasis on the use of human in vitro models of cells associated with the BBB to unravel the pathway of entry for these bacteria to the CNS and to reveal the molecular and cellular pathways involved in initiating the AD-like pathology. In conclusion, evidence demonstrate that bacteria associated with periodontitis and their virulence factors are capable of inflecting damage to the BBB and have a role in giving rise to pathology similar to that found in AD.

Drug Delivery Systems for Targeting Blood Brain Barrier

2021 ◽  
pp. 257-268
Author(s):  
Iara Baldim ◽  
Adriana M. Ribeiro ◽  
João Dias-Ferreira ◽  
Wanderley P. Oliveira ◽  
Francisco M. Gama ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Brain Barrier ◽  
Blood Brain

Application of the phage display technology for the development of peptide-mediated drug delivery systems through the blood-brain barrier

2021 ◽  
Vol 22 ◽  
Author(s):  
Viana Manrique-Suárez ◽  
Nelson Santiago Vispo ◽  
Oliberto Sánchez Ramos
Keyword(s):  
Drug Delivery ◽  
Phage Display ◽  
Blood Brain Barrier ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Brain Barrier ◽  
Phage Display Technology ◽  
Blood Brain ◽  
Display Technology ◽  
The Brain

: The main obstacle to biopharmaceutical delivery in therapeutic concentration into the brain for treating neurological disorders is the presence of the blood-brain barrier (BBB). The physiological process of receptor-mediated transcytosis (RMT) to transport cargo through the brain endothelial cells toward brain parenchyma has prompted researchers to search for non-natural ligands that can be used to transport drugs across the BBB. Conjugation of drugs to RMT ligands would be an effective strategy for its delivery to the central nervous system. An attractive approach to identify novel transcytosing ligands is the screening by phage display combinatorial libraries. The main technology strength lies in the large variety of exogenous peptides or proteins displayed on the phage's surface. Here, we provide a mini-review of phage display technology using in vitro and in vivo BBB models for the development of peptide-mediated drug delivery systems.

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