SCDT-50. SURFACE MODIFIED LIPOSOMES FOR EFFECTIVE DELIVERY OF THERAPEUTIC AGENTS ACROSS THE BLOOD BRAIN BARRIER

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.

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Receptor Targeted Polymeric Nanostructures Capable of Navigating across the Blood-Brain Barrier for Effective Delivery of Neural Therapeutics

ACS Chemical Neuroscience ◽

10.1021/acschemneuro.7b00207 ◽

2017 ◽

Vol 8 (10) ◽

pp. 2105-2117 ◽

Cited By ~ 6

Author(s):

Taru Dube ◽

Sonika Chibh ◽

Jibanananda Mishra ◽

Jiban Jyoti Panda

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Blood Brain ◽

Effective Delivery

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Bypassing the blood-brain barrier: delivery of therapeutic agents by macrophages

10.1117/12.846958 ◽

2010 ◽

Author(s):

Henry Hirschberg ◽

Seung-Kuk Baek ◽

Young Jik Kwon ◽

Chung-Ho Sun ◽

Steen J. Madsen

Keyword(s):

Blood Brain Barrier ◽

Therapeutic Agents ◽

Brain Barrier ◽

Blood Brain

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Photomodulation of lymphatic delivery of liposomes to the brain bypassing the blood-brain barrier: new perspectives for glioma therapy

Nanophotonics ◽

10.1515/nanoph-2021-0212 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Oxana Semyachkina-Glushkovskaya ◽

Ivan Fedosov ◽

Alexander Shirokov ◽

Elena Vodovozova ◽

Anna Alekseeva ◽

...

Keyword(s):

Blood Brain Barrier ◽

Significant Contribution ◽

Brain Barrier ◽

Brain Drug Delivery ◽

Blood Brain ◽

Effective Delivery ◽

The Central Nervous System ◽

Free Generation ◽

Lymphatic Delivery ◽

The Brain

Abstract The blood-brain barrier (BBB) has a significant contribution to the protection of the central nervous system (CNS). However, it also limits the brain drug delivery and thereby complicates the treatment of CNS diseases. The development of safe methods for an effective delivery of medications and nanocarriers to the brain can be a revolutionary step in the overcoming this limitation. Here, we report the unique properties of the lymphatic system to deliver tracers and liposomes to the brain meninges, brain tissues, and glioma in rats. Using a quantum-dot-based 1267 nm laser (for photosensitizer-free generation of singlet oxygen), we clearly demonstrate photostimulation of lymphatic delivery of liposomes to glioma as well as lymphatic clearance of liposomes from the brain. These pilot findings open promising perspectives for photomodulation of lymphatic delivery of drugs and nanocarriers to the brain pathology bypassing the BBB. The lymphatic “smart” delivery of liposomes with antitumor drugs in the new brain tumor branches might be a breakthrough strategy for the therapy of gliomas.

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Comparison of polypeptides that bind the transferrin receptor for targeting gold nanocarriers

PLoS ONE ◽

10.1371/journal.pone.0252341 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252341

Author(s):

Conor McQuaid ◽

Andrea Halsey ◽

Maëva Dubois ◽

Ignacio Romero ◽

David Male

Keyword(s):

Blood Brain Barrier ◽

Transferrin Receptor ◽

Cyclic Peptides ◽

Cyclic Peptide ◽

Therapeutic Agents ◽

Brain Barrier ◽

Brain Endothelium ◽

Linear Peptide ◽

Blood Brain ◽

Dividing Cells

The ability to target therapeutic agents to specific tissues is an important element in the development of new disease treatments. The transferrin receptor (TfR) is one potential target for drug delivery, as it expressed on many dividing cells and on brain endothelium, the key cellular component of the blood-brain barrier. The aim of this study was to compare a set of new and previously-described polypeptides for their ability to bind to brain endothelium, and investigate their potential for targeting therapeutic agents to the CNS. Six polypeptides were ranked for their rate of endocytosis by the human brain endothelial cell line hCMEC/D3 and the murine line bEnd.3. One linear polypeptide and two cyclic polypeptides showed high rates of uptake. These peptides were investigated to determine whether serum components, including transferrin itself affected uptake by the endothelium. One of the cyclic peptides was strongly inhibited by transferrin and the other cyclic peptide weakly inhibited. As proof of principle the linear peptide was attached to 2nm glucose coated gold-nanoparticles, and the rate of uptake of the nanoparticles measured in a hydrogel model of the blood-brain barrier. Attachment of the TfR-targeting polypeptide significantly increased the rates of endocytosis by brain endothelium and increased movement of nanoparticles across the cells.

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