Ultrasound-mediated yew alcohol treats glioma through the blood-brain barrier

Paclitaxel (PTX) is a common cancer chemotherapy drug, but due to the presence of blood-brain barrier (BBB), PTX can not enter the brain, there is no obvious effect on glioma.
study reported that low-intensity pulsed ultrasound (LIPU) and micro-bubble injections can instantly turn on BBB, which mediates drugs into the brain.
Daniel Y. Zhang of Neurosurgery at Northwestern University's Feinberg School of Medicine analyzed two FDA-approved PTX preparations, yew alcohol-albumin binding to yew alcohol (ABX) and Cremorne-soluble yew alcohol (CrEL-PT) X), in conjunction with LIPU administration of drug distribution, toxicity, and efficacy in mouse models of human-derived glioma xenografts (patient-derived glioma xenografts, PDX), the results of which were published in the January 2020 issue of the journal Clinical Cancer Research.
Study Methods Researchers measured the biological distribution of ultrasound and non-ultrasound-treated PTX in naked mice, and compared the distribution and efficacy of ABX and CrEL-PTX in LIPU-mediated tumors before and after LIPU, while assessing the toxicity of yew alcohol.
study used a 1 MHz LIPU device (SonoCloud ®) for ultrasound processing and fluorescent confirmation and BBB destruction mapping.
the study showed that ABX was similar to CrEL-PTX in-body anti-glioma activity.
the use of low-intensity pulse ultrasound-mediated BBB damage, so that the concentration of yew alcohol in the brain increased by 3-5 times, enhance the therapeutic effect of PTX.
and ABX-treated PDX mice had a longer lifetime than crEL-PTX and the control group.
, LIPU damage to BBB is an effective means to increase the concentration of PTX in glioma.
toxicity studies have shown that mice with the same dose of ABX are better resistant than CrEL-PTX.
the same dose (12 mg/kg) crEL-PTX after ultrasound treatment is more neurotoxic than ABX and can cause large-scale cerebral infarction and bleeding.
can also occur significant neurotoxicity if crEL is used alone.
, crEL-PTX's neurotoxicity is largely related to CrEL solvents.
neurotoxicity of large doses of ABX after ultrasound treatment appeared to be related to frequency of use, with 11.5% of mice given a dose of ABX at 24 mg/kg per week, and 11.5% of mice with a tumor had neurotoxic deaths.
when the frequency of ABX dosing was reduced to twice a week, the mortality rate decreased significantly.
this occurs in small animals, and in primate models and human subjects, ultrasound-mediated BBB openness has been shown to be safe and reliable.
conclusions, ultrasound-assisted yew alcohol is a feasible and effective new method for treating cerebral glioma.
ABX has better BBB penetration and tolerance than CrEL-PTX.
, ABX is the preferred preparation for further clinical studies to treat gliomas.
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