Current Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier

Teleanu, Raluca Ioana; Preda, Manuela Daniela; Niculescu, Adelina-Gabriela; Vladâcenco, Oana Aurelia; Radu, C; Grumezescu, Valentina; Teleanu, Daniel Mihai

doi:10.3390/pharmaceutics14050987

Cited by 69 publications

(41 citation statements)

References 189 publications

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“…In GBMs, the BTB is often disrupted as evidenced by MRI and PET images (Sarkaria et al, 2018). Nanoparticles have been used in attempts to traverse BBB more effectively (Baghirov et al, 2018; Clark & Davis, 2015; Teleanu et al, 2022). Most of these strategies involved targeting different components of BBB and techniques related to the temporary opening of BBB.…”

Section: Brain Cancer: Little Studied Cancer At Preclinical and Clini...mentioning

confidence: 99%

Current landscape of treating different cancers using nanomedicines: Trends and perspectives

Morales,

Grodzinski

2023

WIREs Nanomed Nanobiotechnol

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The efforts to use novel nanotechnologies in medicine and cancer have been widespread. In order to understand better the focus areas of cancer nanomedicine research to date, we conducted a survey of nanomedicine developmental and clinical research in conjunction with treatment of various cancers. The survey has been performed based on number of publications, rate of citations, entry into clinical trials, and funding rates by the National Cancer Institute. Our survey indicates that breast and brain cancers are the most and one of the least studied by nanotechnology researchers, respectively. Breast cancer nano‐therapies seem to also be most likely to achieve clinical translation as the number of publications produced, amount of funding, total citations, and clinical trials (active and completed) are the highest when compared with research in other cancers. Brain cancer, despite its low survival, has capture much less attention of nanomedicine research community as survey indicated, although nanotechnology can offer novel approaches which can address brain cancer challenges.This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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Section: Brain Cancer: Little Studied Cancer At Preclinical and Clini...mentioning

confidence: 99%

Current landscape of treating different cancers using nanomedicines: Trends and perspectives

Morales,

Grodzinski

2023

WIREs Nanomed Nanobiotechnol

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“…Because of their lipophilic character, SLNs and other lipid formulations have been shown to protect medicines against presystemic metabolization while improving membrane absorption and uptake 15 . In this process, SLNs can help bypass the barriers and enhance the administration of medications, especially lipophilic drugs 16 . For instance, SLNs have the potential to enhance the penetration of drugs through the skin, particularly for those having small sizes 17 .…”

Section:  Advantages Of Slns Over Various Deliverymentioning

confidence: 99%

Untitled

2023

IJPSR

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Nanoparticles with lipids as a constituent are called "solid lipid nanoparticles" (SLNs). Based on the most recent trends, SLNS is a promising approach for overcoming multiple barriers in drug delivery. Through SLNs, maximized drug payload to the site of action for different pharmaceutical drugs can be achieved. They range in size from 10nm to 1000nm and possess a solid lipid core matrix that aids in the solubilization of lipophilic compounds. The evolution of multidrug resistance therapy against various chemotherapeutic agents, tissue toxicity, and a high prevalence of drug-resistant tumors are the most common impediments in the clinical management of cancer. For more than a decade, SLNs have been widely used as drug delivery systems in the treatment of various cancers due to their low toxicity, high drug bioavailability, and usefulness with hydrophilic and lipophilic drugs. In this review, we discussed the incorporation and controlled delivery of different cytotoxic anti-cancer drugs to target sites using SLNs to treat various malignancies.

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“…4 The BBB is essential for physiological brain function but restricts the transport of therapeutic agents into the central nervous system (CNS), reducing their clinical effectiveness. 5 importance of improving drug penetration at the level of the BBB, numerous preclinical BBB models have been established…”

Section: ■ Introductionmentioning

confidence: 99%

Patient-Derived Blood-Brain Barrier Model for Screening Copper Bis(thiosemicarbazone) Complexes as Potential Therapeutics in Alzheimer’s Disease

Wasielewska,

Szostak,

McInnes

et al. 2024

ACS Chem. Neurosci.

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Alzheimer's disease (AD) is the most prevalent cause of dementia characterized by a progressive cognitive decline. Addressing neuroinflammation represents a promising therapeutic avenue to treat AD; however, the development of effective antineuroinflammatory compounds is often hindered by their limited blood-brain barrier (BBB) permeability. Consequently, there is an urgent need for accurate, preclinical AD patient-specific BBB models to facilitate the early identification of immunomodulatory drugs capable of efficiently crossing the human AD BBB. This study presents a unique approach to BBB drug permeability screening as it utilizes the familial AD patient-derived induced brain endothelial-like cell (iBEC)-based model, which exhibits increased disease relevance and serves as an improved BBB drug permeability assessment tool when compared to traditionally employed in vitro models. To demonstrate its utility as a small molecule drug candidate screening platform, we investigated the effects of diacetylbis(N(4)-methylthiosemicarbazonato)copper(II) (Cu II (atsm)) and a library of metal bis(thiosemicarbazone) complexes�a class of compounds exhibiting antineuroinflammatory therapeutic potential in neurodegenerative disorders. By evaluating the toxicity, cellular accumulation, and permeability of those compounds in the AD patient-derived iBEC, we have identified 3,4-hexanedione bis(N(4)-methylthiosemicarbazonato)copper(II) (Cu II (dtsm)) as a candidate with good transport across the AD BBB. Furthermore, we have developed a multiplex approach where AD patientderived iBEC were combined with immune modulators TNFα and IFNγ to establish an in vitro model representing the characteristic neuroinflammatory phenotype at the patient's BBB. Here, we observed that treatment with Cu II (dtsm) not only reduced the expression of proinflammatory cytokine genes but also reversed the detrimental effects of TNFα and IFNγ on the integrity and function of the AD iBEC monolayer. This suggests a novel pathway through which copper bis(thiosemicarbazone) complexes may exert neurotherapeutic effects on AD by mitigating BBB neuroinflammation and related BBB integrity impairment. Together, the presented model provides an effective and easily scalable in vitro BBB platform for screening AD drug candidates. Its improved translational potential makes it a valuable tool for advancing the development of metal-based compounds aimed at modulating neuroinflammation in AD.

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Current Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier

Cited by 69 publications

References 189 publications

Current landscape of treating different cancers using nanomedicines: Trends and perspectives

Current landscape of treating different cancers using nanomedicines: Trends and perspectives

Untitled

Patient-Derived Blood-Brain Barrier Model for Screening Copper Bis(thiosemicarbazone) Complexes as Potential Therapeutics in Alzheimer’s Disease

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