Drug Delivery to the Brain across the Blood‐Brain Barrier Using Nanomaterials

Tsou, Yung-Hao; Zhang, Xueqing; He, Zhonghu; Syed, Sahla; Xu, Xiaoyang

doi:10.1002/smll.201801588

Cited by 24 publications

(22 citation statements)

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“…56,57 The completion of the reaction was confirmed by 1 H NMR showing complete disappearance of allyl signals at d 5.8, 5.2 and 3.9 ppm and appearance of a sharp peak for BOC protons at d 1.3 ppm ( Figure 7B). The BOC was then deprotected using TFA following similar conditions as described earlier to afford bifunctional ether linked dendrimer (13). The analysis of proton NMR clearly revealed the disappearance of tert-butyl peak corresponding to BOC protons in the spectrum ( Figure 7B).…”

Section: Another Synthetic Approach For Conjugation Of Nac On Dendrmentioning

confidence: 87%

“…Recently, the field of drug delivery has been revolutionized with a plethora of innovative nanotechnology-based products which can effectively diffuse through the biological barricades within the body and deliver payloads of drugs, DNA, proteins or peptides to injured or diseased cells and tissues. [11][12][13][14][15][16] Despite the significant growth in the field of nanotechnology, nanoparticles face challenges during clinical translation. Major challenges include reproducible scale-up of the synthesis, and definition of the benchmarks of the final product and the stability.…”

Section: Introductionmentioning

confidence: 99%

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Scalable synthesis and validation of PAMAM dendrimer‐N‐acetyl cysteine conjugate for potential translation

Sharma

Kambhampati

et al. 2018

Bioengineering & Transla Med

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Dendrimer‐N‐acetyl cysteine (D‐NAC) conjugate has shown significant promise in multiple preclinical models of brain injury and is undergoing clinical translation. D‐NAC is a generation‐4 hydroxyl‐polyamidoamine dendrimer conjugate where N‐acetyl cysteine (NAC) is covalently bound through disulfide linkages on the surface of the dendrimer. It has shown remarkable potential to selectively target and deliver NAC to activated microglia and astrocytes at the site of brain injury in several animal models, producing remarkable improvements in neurological outcomes at a fraction of the free drug dose. Here we present a highly efficient, scalable, greener, well‐defined route to the synthesis of D‐NAC, and validate the structure, stability and activity to define the benchmarks for this compound. This newly developed synthetic route has significantly reduced the synthesis time from three weeks to one week, uses industry‐friendly solvents/reagents, and involves simple purification procedures, potentially enabling efficient scale up.

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Section: Another Synthetic Approach For Conjugation Of Nac On Dendrmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Scalable synthesis and validation of PAMAM dendrimer‐N‐acetyl cysteine conjugate for potential translation

Sharma

Kambhampati

et al. 2018

Bioengineering & Transla Med

View full text Add to dashboard Cite

show abstract

“…These data suggest that CBD, by triggering 5-HT1A and PPARγ receptors, could have a protective effect against BBB malfunction caused by ischemic events. Further, in vitro experiments on BMEC showed that CBD induces proliferation, migration, tubulogenesis, and trans-endothelial electrical resistance increase, indicating that CBD might be useful for the positive modulation of the BBB as a future treatment in ischemic stroke [51].…”

Section: Cannabinoids and Blood-brain Barriermentioning

confidence: 99%

“…From this point of view, since it is known that effective brain drug delivery should not be based only on passive targeting, active targeting through the use of nanomedicines into the brain has been investigated. In regard to this, the use of nanocarriers can be considered as an alternative to enhance the passage across the BBB [51]. Brain active targeting is formed on the transformation of nanoparticles with elements able to trigger transcytosis mediated by receptors in the brain by means of binding with molecules acting as transporters overexpressed by brain endothelial cells.…”

Section: Cannabidiol and Diseases Involving Blood-brain Barrier Breakmentioning

confidence: 99%

Cannabinoids, Blood–Brain Barrier, and Brain Disposition

et al. 2020

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Potential therapeutic actions of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are based on their activity as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds. THC and CBD lipophilicity and their neurological actions makes them candidates as new medicinal approaches to treat central nervous system (CNS) diseases. However, they show differences about penetrability and disposition in the brain. The present article is an overview about THC and CBD crossing the blood-brain barrier (BBB) and their brain disposition. Several findings indicate that CBD can modify the deleterious effects on BBB caused by inflammatory cytokines and may play a pivotal role in ameliorating BBB dysfunction consequent to ischemia. Thus supporting the therapeutic potential of CBD for the treatment of ischemic and inflammatory diseases of CNS. Cannabinoids positive effects on cognitive function could be also considered through the aspect of protection of BBB cerebrovascular structure and function, indicating that they may purchase substantial benefits through the protection of BBB integrity. Delivery of these cannabinoids in the brain following different routes of administration (subcutaneous, oral, and pulmonary) is illustrated and commented. Finally, the potential role of cannabinoids in drug-resistance in the clinical management of neurological or psychiatric diseases such as epilepsy and schizophrenia is discussed on the light of their crossing the BBB.

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“…1,2 However, it is also a big challenge for the clinical application of CNS drugs because of its ability of hindering drug accumulation and uptake in brain cells. 3,4 So, the safe and efficient transport system for CNS drugs across the BBB is becoming a promising strategy for the treatment of cerebrovascular disease and CNS illness. 5,6 In recent researches, some delivery systems of nanoparticles (NPs) show a high permeability across the BBB and have the potential to serve as a new nanomedicine.…”

Section: Introductionmentioning

confidence: 99%

Conjugation of vitamin E-TPGS and guar gum to carry borneol for enhancing blood–brain barrier permeability

et al. 2018

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Herb borneol is usually used in clinics for the treatment of central nervous system illness, for its ability of blood-brain barrier permeability, although its poor water solubility and poor bioavailability limit its clinical application to some degree. In this study, we developed a novel nanoparticle combining the benefits of vitamin E d-ɑ-tocopheryl poly(ethylene glycol) succinate (E-TPGS) (or TPGS) and guar gum to get TPGS-g-guar gum as a drug delivery system to carry borneol, which could improve the solubility of borneol and increase the drug-loading capacity efficiently. The results showed that TPGS-g-guar gum nanoparticles delivery system was suitable to carry borneol and release the drug effectively, and TPGS-g-guar gum/borneol nanoparticles would be a potential platform for improving the treatment of central nervous system illness and cerebrovascular disease.

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Drug Delivery to the Brain across the Blood‐Brain Barrier Using Nanomaterials

Cited by 24 publications

References 0 publications

Scalable synthesis and validation of PAMAM dendrimer‐N‐acetyl cysteine conjugate for potential translation

Scalable synthesis and validation of PAMAM dendrimer‐N‐acetyl cysteine conjugate for potential translation

Cannabinoids, Blood–Brain Barrier, and Brain Disposition

Conjugation of vitamin E-TPGS and guar gum to carry borneol for enhancing blood–brain barrier permeability

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