A Historical Review of Brain Drug Delivery

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(6), P. 1283 - 1283

Published: June 16, 2022

The history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a for syphilis, salvarsan, did not enter brain, due to presence blood–brain barrier (BBB). Owing restricted transport across BBB, FDA-approved drugs CNS have been generally limited lipid-soluble small molecules. Drugs do cross BBB can be re-engineered on endogenous carrier-mediated and receptor-mediated systems, which were identified during 1970s–1980s. By 1990s, multitude technologies emerged, including trans-cranial delivery, CSF disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, biologics. advantages limitations each these are critically reviewed.

Language: Английский

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Immune Checkpoint Inhibition in GBM Primed with Radiation by Engineered Extracellular Vesicles

ACS Nano, Journal Year: 2022, Volume and Issue: 16(2), P. 1940 - 1953

Published: Jan. 31, 2022

The lack of safe and effective delivery across the blood-brain barrier profound immune suppressive microenvironment are two main hurdles to glioblastoma (GBM) therapies. Extracellular vesicles (EVs) have been used as therapeutic vehicles GBM but with limited efficacy. We hypothesized that EV can be enhanced by (i) modifying surface a brain-tumor-targeting cyclic RGDyK peptide (RGD-EV) (ii) using bursts radiation for accumulation. In addition, EVs were loaded small interfering RNA (siRNA) against programmed cell death ligand-1 (PD-L1) checkpoint blockade. show this EV-based strategy dramatically targeting efficiency RGD-EV murine GBM, while siRNA reversed radiation-stimulated PD-L1 expression on tumor cells recruited tumor-associated myeloid cells, offering synergistic effect. combined therapy significantly increased CD8

Language: Английский

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Cell-derived nanovesicle-mediated drug delivery to the brain: Principles and strategies for vesicle engineering

Molecular Therapy, Journal Year: 2022, Volume and Issue: 31(5), P. 1207 - 1224

Published: Oct. 17, 2022

Developing strategies toward safe and effective drug delivery into the central nervous system (CNS) with improved targeting abilities reduced off-target effects is crucial. CNS-targeted carriers made of synthetic molecules raise concerns about their biodegradation, clearance, immune responses, neurotoxicity. Cell-derived nanovesicles (CDNs) have recently been applied in delivery, because intrinsic stability, biocompatibility, inherent homing capability, ability to penetrate through biological barriers, including blood-brain barrier. Among these CDNs, extracellular vesicles exosomes are most studied surface can be engineered modified cater brain targeting. In this review, we focus on application CDNs brain-targeted treat neurological diseases. We cover developed methods exosome derivation engineering, exosome-like particles, hybrid exosomes, exosome-associated adeno-associated viruses, envelope protein nanocages. Finally, discuss limitations project future development CDN-based systems, conclude that hold great potential treatment

Language: Английский

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Recent progresses in exosome-based systems for targeted drug delivery to the brain

Journal of Controlled Release, Journal Year: 2022, Volume and Issue: 348, P. 723 - 744

Published: June 23, 2022

Language: Английский

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Biological Features of Extracellular Vesicles and Challenges

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: June 24, 2022

Extracellular vesicles (EVs) are with a lipid bilayer membrane on the outside, which widely found in various body fluids and contain biological macromolecules such as DNA, RNA, lipids proteins inside. EVs were once thought to be for removal of waste materials, but now known involved variety pathophysiological processes many diseases. This study examines advantage challenges associated their application. A more rational use advantageous properties composition specificity, specific targeting, circulatory stability, active penetration barriers, high efficient drug delivery vehicles anticancer vaccines, oxidative phosphorylation activity enzymatic activity, resolution shortcomings isolation purification methods, storage conditions pharmacokinetics biodistribution patterns during will facilitate clinical application EVs.

Language: Английский

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Insights into Exosome Transport through the Blood–Brain Barrier and the Potential Therapeutical Applications in Brain Diseases

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(4), P. 571 - 571

Published: April 10, 2023

Drug delivery to the central nervous system (CNS) is limited due presence of blood–brain barrier (BBB), a selective physiological located at brain microvessels that regulates flow cells, molecules and ions between blood brain. Exosomes are nanosized extracellular vesicles expressed by all cell types function as cargos, allowing for communication cells. The exosomes were shown cross or regulate BBB in healthy disease conditions. However, mechanistic pathways which have not been fully elucidated yet. In this review, we explore transport mechanisms through BBB. A large body evidence suggests exosome occurs primarily transcytosis. transcytosis influenced several regulators. Inflammation metastasis also enhance trafficking across We shed light on therapeutical applications treating diseases. Further investigations essential provide clearer insights related treatment.

Language: Английский

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Protein corona and exosomes: new challenges and prospects

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: March 27, 2023

Recent advances in extracellular vesicle (EVs) detection and isolation methods have led to the development of novel therapeutic modalities. Among different types EVs, exosomes (Exos) can transfer signaling biomolecules exhibit several superior features compared whole-cell-based therapies. Therapeutic factors are normally loaded into Exo lumen or attached their surface for improving on-target delivery rate regenerative outcomes. Despite these advantages, there limitations application Exos vivo conditions. It was suggested that a set proteins other biological compounds adsorbed around aqueous phases constitute an external layer named protein corona (PC). Studies shown PC affect physicochemical properties synthetic natural nanoparticles (NPs) after introduction biofluids. Likewise, is generated especially This review article preliminary attempt address interfering effects on bioactivity effects. Video Abstract.

Language: Английский

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Outer Membrane Vesicles Released from Garlic Exosome‐like Nanoparticles (GaELNs) Train Gut Bacteria that Reverses Type 2 Diabetes via the Gut‐Brain Axis

Small, Journal Year: 2024, Volume and Issue: 20(20)

Published: Jan. 15, 2024

Gut microbiota function has numerous effects on humans and the diet consume emerged as a pivotal determinant of gut function. Here, new concept that can be trained by diet-derived exosome-like nanoparticles (ELNs) to release healthy outer membrane vesicles (OMVs) is introduced. Specifically, OMVs released from garlic ELN (GaELNs) human Akkermansia muciniphila (A. muciniphila) reverse high-fat diet-induced type 2 diabetes (T2DM) in mice. Oral administration GaELNs A. traffick brain where they are taken up microglial cells, resulting inhibition inflammation. treatment increases levels OMV Amuc-1100, P9, phosphatidylcholines. Increasing Amuc-1100 P9 leads increasing GLP-1 plasma level. phosphatidylcholines required for cGas STING-mediated inflammation GLP-1R crosstalk with insulin pathway expression Insulin Receptor Substrate (IRS1 IRS2) targeted cells. These findings reveal molecular mechanism whereby plant nanoparticle-trained bacteria regulate genes expressed brain, have implications dysfunction caused metabolic syndrome.

Language: Английский

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Applications, challenges and prospects of mesenchymal stem cell exosomes in regenerative medicine

Stem Cell Research & Therapy, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 28, 2021

Abstract Recent advances in the identification and application of different stem cell types have offered alternative therapeutic approaches for clinicians. The lack successful engraftment, migration into injured site, loss functionality viability, ethical issues, shortage donated allogeneic cells possibility transmission infectious are main challenges associated with direct transplantation. discovery research on exosomes led to rise hopes alleviation pathologies regenerative medicine. Exo nano-sized extracellular vesicles (40–150 nm) released by each type. These nanoparticles participate cell-to-cell communication a paracrine manner. It is thought that can circumvent several drawbacks related whole-cell therapies. Because their appropriate size stability, touted as bullets transferring signaling factors acceptor Despite these advantages, technologies isolation purification challenging because heterogeneity exosomal cargo. standard GMP-grade protocols hurdle limits extensive clinical setting. Here, authors aimed inspire logical realistic vision about problems

Language: Английский

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Functional Extracellular Vesicles for Regenerative Medicine

Small, Journal Year: 2022, Volume and Issue: 18(36)

Published: March 23, 2022

The unique biological characteristics and promising clinical potential of extracellular vesicles (EVs) have galvanized EV applications for regenerative medicine. Recognized as important mediators intercellular communication, naturally secreted EVs the potential, innate biotherapeutics, to promote tissue regeneration. Although emerged novel therapeutic agents, challenges related transition led further functionalization. In recent years, various engineering approaches such preconditioning, drug loading, surface modification been developed potentiate outcomes EVs. Also, limitations natural addressed by development artificial that offer advantages in terms production yield isolation methodologies. this review, an updated overview current techniques is provided functionalization advances EVs, particularly scope

Language: Английский

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