Nanoparticles crossing the blood-brain barrier [Neurosurgery Wiki]

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====== Nanoparticles crossing the blood-brain barrier ======

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The blood-brain barrier (BBB) is a highly selective permeability barrier that protects the brain from potentially harmful substances while allowing essential nutrients to pass through. This barrier poses a significant challenge for delivering therapeutic agents to treat brain diseases. However, nanoparticles have emerged as a promising tool for crossing the BBB due to their unique properties.

Mechanisms of BBB Crossing
Transcytosis:

Receptor-mediated transcytosis: Nanoparticles are functionalized with ligands that bind to specific receptors on the endothelial cells of the BBB, such as transferrin receptors or low-density lipoprotein receptors. This binding triggers the engulfment and transport of nanoparticles across the BBB.
Adsorptive-mediated transcytosis: Positively charged nanoparticles interact with the negatively charged cell membranes, facilitating their uptake and transport across the BBB.
Paracellular Transport:

Temporary disruption or modulation of tight junctions between endothelial cells can allow nanoparticles to pass through. However, this method is less specific and carries a higher risk of damaging the BBB integrity.
Carrier-mediated transport:

Nanoparticles can exploit existing transport mechanisms by mimicking the structure of endogenous molecules that are actively transported across the BBB.
Types of Nanoparticles
Liposomes:

These are spherical vesicles with a phospholipid bilayer, which can encapsulate both hydrophilic and hydrophobic drugs. Surface modifications with targeting ligands can enhance their BBB crossing ability.
Polymeric Nanoparticles:

Made from biocompatible and biodegradable polymers, these nanoparticles can be engineered to release their payload in a controlled manner. Examples include PLGA (polylactic-co-glycolic acid) nanoparticles.
Solid Lipid Nanoparticles (SLNs):

These are made from solid lipids and offer a stable and controlled release system for drug delivery.
Gold Nanoparticles:

Known for their ease of functionalization and biocompatibility, gold nanoparticles can be conjugated with various molecules to enhance BBB penetration.
Dendrimers:

These are highly branched, tree-like structures with multiple functional groups that can be tailored for drug delivery and targeting.
Applications in Brain Diseases
Cancer Treatment:

Nanoparticles can deliver chemotherapeutic agents directly to brain tumors, reducing systemic toxicity and improving drug efficacy.
Neurodegenerative Diseases:

Targeted delivery of therapeutic agents, such as antioxidants or neuroprotective drugs, can potentially slow the progression of diseases like Alzheimer's and Parkinson's.
Stroke:

Nanoparticles can be used to deliver thrombolytic agents or neuroprotective drugs to minimize brain damage following a stroke.
Infections:

Targeted delivery of antimicrobial agents to the brain can treat infections such as bacterial meningitis.
Challenges and Considerations
Safety and Toxicity:

Long-term safety and potential toxicity of nanoparticles must be thoroughly evaluated, as they can accumulate in the brain and other tissues.
Immune Response:

Nanoparticles can elicit an immune response, leading to rapid clearance from the bloodstream and reduced efficacy.
Scaling Up Production:

Consistent and scalable production methods are required to ensure the clinical viability of nanoparticle-based therapies.
Regulatory Hurdles:

Comprehensive regulatory guidelines must be established for the approval of nanoparticle-based drugs.
Nanoparticles represent a promising avenue for overcoming the challenges of delivering therapeutics across the BBB, offering potential breakthroughs in the treatment of various brain diseases. However, ongoing research and development are crucial to address the associated challenges and ensure their safe and effective use in clinical settings.
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The blood-brain barrier (BBB) constitutes a microvascular network responsible for excluding most drugs from the brain. Treatment of brain tumors is limited by the impermeability of the BBB and, consequently, survival outcomes for malignant brain tumors remain poor. Nanoparticles (NPs) represent a potential solution to improve drug transport to brain tumors, given their small size and capacity to target tumor cells
((Hersh AM, Alomari S, Tyler BM. Crossing the Blood-Brain Barrier: Advances in Nanoparticle Technology for Drug Delivery in Neuro-Oncology. Int J Mol Sci. 2022 Apr 9;23(8):4153. doi: 10.3390/ijms23084153. PMID: 35456971; PMCID: PMC9032478.))

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Nanoparticles crossing the blood-brain barrier need specific design for normal, neurodegenerative, or cancerous brain conditions
((Ljubimova JY, Holler E, Black KL, Ljubimov AV. Nanoparticles crossing blood-brain barrier need specific design for normal, neurodegenerative or cancerous brain conditions. Nanomedicine (Lond). 2024 Aug 7:1-4. doi: 10.1080/17435889.2024.2380241. Epub ahead of print. PMID: 39109486.)).