Brain accumulation of tivozanib is restricted by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) in mice

Wang, Jing; Bruin, Michiel de; Gan, Changpei; Lebre, Maria C.; Rosing, Hilde; Beijnen, Jos H.; Schinkel, Alfred H.

doi:10.1016/j.ijpharm.2020.119277

Cited by 12 publications

(7 citation statements)

References 36 publications

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“…Moreover, most of the anti-cancer drugs are substrates for ATP-binding cassette (ABC) efflux transporters, contributing to the low drug accumulation in the brain [ 5 ]. Brain uptake of TKIs including gefitinib, regorafenib, and tivozanib is reported to be restricted by ABC transporters [ 71 , 72 , 73 ]. Even if the TKI is able to cross the BBB, evidence indicates that TKIs do not reach sufficient intra-tumoral therapeutic concentrations [ 5 ].…”

Section: Clinical Trials Of Tkis In Treatment Of Gbm and Disappointin...mentioning

confidence: 99%

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Brar

Jose

et al. 2022

Pharmaceutics

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Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality rates. Due to its invasiveness, heterogeneity, and incomplete resection, the treatment is very challenging. Targeted therapies such as tyrosine kinase inhibitors (TKIs) have great potential for GBM treatment, however, their efficacy is primarily limited by poor brain distribution due to the presence of the blood–brain barrier (BBB). This review focuses on the potential of TKIs in GBM therapy and provides an insight into the reasons behind unsuccessful clinical trials of TKIs in GBM despite the success in treating other cancer types. The main section is dedicated to the use of promising drug delivery strategies for targeted delivery to brain tumors. Use of brain targeted delivery strategies can help enhance the efficacy of TKIs in GBM. Among various drug delivery approaches used to bypass or cross BBB, utilizing nanocarriers is a promising strategy to augment the pharmacokinetic properties of TKIs and overcome their limitations. This is because of their advantages such as the ability to cross BBB, chemical stabilization of drug in circulation, passive or active targeting of tumor, modulation of drug release from the carrier, and the possibility to be delivered via non-invasive intranasal route.

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Section: Clinical Trials Of Tkis In Treatment Of Gbm and Disappointin...mentioning

confidence: 99%

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Brar

Jose

et al. 2022

Pharmaceutics

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“… 167 , 168 The use of nonionic surfactants such as polysorbate 80 may also help nanoparticles to accumulate in the brain for a long time due to their inhibitory effect on P-glycoprotein (Pgp/ABCB1, a mechanism of foreign body efflux in the brain). 169 , 170 Other substances that use this mechanism of brain transport are poly (butyl cyanoacrylate) (PBCA) and PLGA. 171 Wilson et al prepared surfactant-coated nanoparticles (rivastigmine-encapsulated PBCA nanoparticles coated with polysorbate 80) and quantitatively evaluated their transport to the brain.…”

Section: Application Of Surfactant-coated Nanoparticles In Nanomedicinementioning

confidence: 99%

A Critical Review of the Use of Surfactant-Coated Nanoparticles in Nanomedicine and Food Nanotechnology

Miyazawa¹,

Itaya²,

Burdeos³

et al. 2021

IJN

104

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Surfactants, whose existence has been recognized as early as 2800 BC, have had a long history with the development of human civilization. With the rapid development of nanotechnology in the latter half of the 20th century, breakthroughs in nanomedicine and food nanotechnology using nanoparticles have been remarkable, and new applications have been developed. The technology of surfactant-coated nanoparticles, which provides new functions to nanoparticles for use in the fields of nanomedicine and food nanotechnology, is attracting a lot of attention in the fields of basic research and industry. This review systematically describes these "surfactant-coated nanoparticles" through various sections in order: 1) surfactants, 2) surfactant-coated nanoparticles, application of surfactant-coated nanoparticles to 3) nanomedicine, and 4) food nanotechnology. Furthermore, current progress and problems of the technology using surfactant-coated nanoparticles through recent research reports have been discussed.

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“…The most common ABC transporters are P-glycoprotein (P-gp; also known as ABCB1), and breast cancer resistance protein (BCRP; also known as ABCG2) [ 79 ]. For instance, brain accumulation of TKIs such as regorafenib, gefitinib, and tivozanib is restricted by P-gp and BCRP [ 81 , 82 , 83 ]. Some other studies showed that oral administration of Imatinib resulted only in a marginal flux across the blood-brain barrier [ 84 , 85 ].…”

Section: Factors Limiting the Effectiveness Of Tkis In Gbmmentioning

confidence: 99%

Tyrosine Kinase Inhibitors in Adult Glioblastoma: An (Un)Closed Chapter?

Aldaz

Arozarena

2021

Cancers

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Glioblastoma (GBM) is the most common and lethal form of malignant brain tumor. GBM patients normally undergo surgery plus adjuvant radiotherapy followed by chemotherapy. Numerous studies into the molecular events driving GBM highlight the central role played by the Epidermal Growth Factor Receptor (EGFR), as well as the Platelet-derived Growth Factor Receptors PDGFRA and PDGFRB in tumor initiation and progression. Despite strong preclinical evidence for the therapeutic potential of tyrosine kinase inhibitors (TKIs) that target EGFR, PDGFRs, and other tyrosine kinases, clinical trials performed during the last 20 years have not led to the desired therapeutic breakthrough for GBM patients. While clinical trials are still ongoing, in the medical community there is the perception of TKIs as a lost opportunity in the fight against GBM. In this article, we review the scientific rationale for the use of TKIs targeting glioma drivers. We critically analyze the potential causes for the failure of TKIs in the treatment of GBM, and we propose alternative approaches to the clinical evaluation of TKIs in GBM patients.

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Brain accumulation of tivozanib is restricted by ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein) in mice

Cited by 12 publications

References 36 publications

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

A Critical Review of the Use of Surfactant-Coated Nanoparticles in Nanomedicine and Food Nanotechnology

Tyrosine Kinase Inhibitors in Adult Glioblastoma: An (Un)Closed Chapter?

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