Blood-Brain Delivery Methods Using Nanotechnology

Teleanu, Daniel Mihai; Chircov, Cristina; Grumezescu, Alexandru Mihai; Volceanov, Adrian; Teleanu, Raluca Ioana

doi:10.3390/pharmaceutics10040269

Cited by 207 publications

(130 citation statements)

References 84 publications

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“…The BBB restricts the delivery of therapeutics to the brain. Overall, 98% of sMDs and probably all TPs cannot cross the barrier by free diffusion [31][32][33]. In the last decade, intense investigation allowed the discovery of new strategies to increase brain penetration of existing therapeutics (invasive, pharmacological, and physiological) [34][35][36].…”

Section: Strategies To Overcome the Bbbmentioning

confidence: 99%

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

et al. 2020

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The incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood–brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells.

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Section: Strategies To Overcome the Bbbmentioning

confidence: 99%

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

et al. 2020

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“…80 On a similar note, other studies also demonstrated that the PEGylation contributed to the BBB permeability of different inorganic nanoparticles like silica nanoparticles, carbon nanotubes, etc. 81 Similarly, Ren and coauthors (2012) also demonstrated the role of PEG functionalization on the brain targeting of the oxidized multiwalled carbon nanotube. The oxidized multiwalled carbon nanotube was surface modified with PEG and angipep-2.…”

Section: Inorganic Nanoparticlesmentioning

confidence: 96%

<p>Recent expansions of novel strategies towards the drug targeting into the brain</p>

Alexander¹,

Agrawal²,

Uddin³

et al. 2019

IJN

117

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The treatment of central nervous system (CNS) disorders always remains a challenge for the researchers. The presence of various physiological barriers, primarily the blood–brain barrier (BBB) limits the accessibility of the brain and hinders the efficacy of various drug therapies. Hence, drug targeting to the brain, particularly to the diseased cells by circumventing the physiological barriers is essential to develop a promising therapy for the treatment of brain disorders. Presently, the investigations emphasize the role of different nanocarrier systems or surface modified target specific novel carrier system to improve the efficiency and reduce the side effects of the brain therapeutics. Such approaches supposed to circumvent the BBB or have the ability to cross the barrier function and thus increases the drug concentration in the brain. Although the efficacy of novel carrier system depends upon various physiological factors like active efflux transport, protein corona of the brain, stability, and toxicity of the nanocarrier, physicochemical properties, patient-related factors and many more. Hence, to develop a promising carrier system, it is essential to understand the physiology of the brain and BBB and also the other associated factors. Along with this, some alternative route like direct nose-to-brain drug delivery can also offer a better means to access the brain without exposure of the BBB. In this review, we have discussed the role of various physiological barriers including the BBB and blood-cerebrospinal fluid barrier (BCSFB) on the drug therapy and the mechanism of drug transport across the BBB. Further, we discussed different novel strategies for brain targeting of drug including, polymeric nanoparticles, lipidic nanoparticles, inorganic nanoparticles, liposomes, nanogels, nanoemulsions, dendrimers, quantum dots, etc. along with the intranasal drug delivery to the brain. We have also illustrated various factors affecting the drug targeting efficiency of the developed novel carrier system.

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“…Nanotechnology-based approaches are under intensive study to overcome the blood-brain barrier and deliver the appropriate amount of drug to the specific brain site. Organic nanocarriers include polymeric nanoparticles, liposomes, dendrimers, and micelles, while inorganic nanocarriers include gold nanoparticles, silica nanoparticles, and carbon nanotubes [138]. Further research is expected to understand the blood-brain barrier crossing mechanisms and to improve the efficiency of brain delivery methods using nanotechnology.…”

Section: Kynurenic Acid Analoguesmentioning

confidence: 99%

Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism

2020

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Worldwide, 50 million people suffer from dementia, a group of symptoms affecting cognitive and social functions, progressing severely enough to interfere with daily life. Alzheimer’s disease (AD) accounts for most of the dementia cases. Pathological and clinical findings have led to proposing several hypotheses of AD pathogenesis, finding a presence of positive feedback loops and additionally observing the disturbance of a branch of tryptophan metabolism, the kynurenine (KYN) pathway. Either causative or resultant of dementia, elevated levels of neurotoxic KYN metabolites are observed, potentially upregulating multiple feedback loops of AD pathogenesis. Memantine is an N-methyl-D-aspartate glutamatergic receptor (NMDAR) antagonist, which belongs to one of only two classes of medications approved for clinical use, but other NMDAR modulators have been explored so far in vain. An endogenous KYN pathway metabolite, kynurenic acid (KYNA), likewise inhibits the excitotoxic NMDAR. Besides its anti-excitotoxicity, KYNA is a multitarget compound that triggers anti-inflammatory and antioxidant activities. Modifying the KYNA level is a potential multitarget strategy to normalize the disturbed KYN pathway and thus to alleviate juxtaposing AD pathogeneses. In this review, the maintenance of KYN metabolism by modifying the level of KYNA is proposed and discussed in search for a novel lead compound against the progression of dementia.

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Blood-Brain Delivery Methods Using Nanotechnology

Cited by 207 publications

References 84 publications

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

<p>Recent expansions of novel strategies towards the drug targeting into the brain</p>

Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism

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