By Allan Mai ‘20
The blood-brain barrier (BBB) protects the brain from infections that enter through the bloodstream. However, this barrier also poses an enormous challenge for researchers developing drugs to specifically target the brain via the blood vessels. For brain tumors specifically, a current method for chemotherapy delivery are Gliadel Wafers: surgeons resect the tumor from the brain and fill the crater left behind with wafers made of polymers that release a chemotherapy drug known as Carmustine. However, this method is extremely invasive, especially for patients who only need the drug and not surgery. While most research is focused on breaking through the BBB, researchers are also seeking to improve current methods that use drugs that are already available.
A new study conducted by Costas D. Arvanitis of Georgia Tech proposes the use of focused ultrasounds (FUS) and microbubbles that have been shown to promote increased uptake of drugs from blood vessels. The authors of the paper experimented by using two drugs known as doxorubicin and ado-trastuzumab emtansine (T-DM1). Both drugs are used to treat brain cancer that spread from breast cancer via a process known as metastasis. When FUS was compared to the control group (non-FUS), a sevenfold increase in the uptake of doxorubicin and a two-fold increase for T-DM1 were reported. Analysis of the data along with modeling of the drug transport shows that FUS in combination with microbubbles alleviates the blood-brain barrier and enhances interstitial convective transport due to increases in hydraulic conductivity. FUS thereby increases the ability of interstitial fluids to move through pores and thus facilitates movement of chemotherapeutic elements.
Cancers like glioblastoma multiforme, which is the most aggressive type of primary brain cancer, continue to yield high mortality rates. This new FUS method, one of many ongoing studies that aim to bypass the obstacle of the blood-brain barrier, is showing promising results.
- C. Arvanitis, et. al., Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood–tumor barrier disruption. PNAS 115 (2018). doi: https://doi.org/10.1073/pnas.1807105115.
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