Brazilian researchers have for the first time tested a drug carrier that can reach the brain, bind to an aggressive type of tumor called glioblastoma multiforme, and release a chemotherapeutic agent. According to an article in the International Journal of Pharmaceutics, the potential treatment was shown to be effective in isolated cells and animal models thanks to a combination of nanotechnology, chemotherapy and a monoclonal antibody.
Glioblastoma multiforme accounts for 60% of all brain tumors in adults and is also the most aggressive type of brain cancer. Even after surgery, radiation therapy, and conventional chemotherapy, patient survival averages about 14 months. One of the reasons is angiogenesis, a process by which the tumor quickly creates its own blood vessels to develop.
“Another difficulty is the blood-brain barrier, which prevents drugs from reaching the tumor,” said Leonardo Di Filippo, a doctoral student and researcher at the School of Pharmaceutical Sciences at São Paulo State University in Araraquara (FCFAr-UNESP).
To address these challenges, Di Filippo worked with researchers from UNESP and two other Brazilian institutions, the University of Campinas (UNICAMP) and the University of São Paulo (USP) in Ribeirão Preto, to combine docetaxel, a powerful chemotherapy drug. , with a nanostructured lipid carrier designed to cross the blood-brain barrier. “We developed a formulation in which the substances combined in a stable way,” he said.
The researchers also linked the carrier to bevacizumab, a monoclonal antibody developed against vascular endothelial growth factor (VEGF) and approved for other uses. “VEGF is the cancer protein that stimulates angiogenesis and tends to overexpress in glioblastoma multiforme,” Di Filippo explained. The goal was to create a formulation capable of penetrating the brain and releasing a chemotherapy drug to destroy the tumor.
“The development of this system with this application is an innovation,” said Marlus Chorili, a UNESP professor and lead researcher on the project, which was supported by FAPESP.
Quality tests
After creating the nanostructured lipid carrier with docetaxel and bevacizumab, the researchers set out to make sure it met some basic criteria. Laboratory tests showed that its size was 128 nanometers, small enough to overcome the blood-brain barrier. In addition, docetaxel trapping was 90% and bevacizumab coupling efficiency was 62%. “These are positive figures, enough to ensure adequate therapeutic concentrations,” Di Filippo said.
The next step was to evaluate the effects of the compound on two glioblastoma cell lines and healthy cells. The nanoparticle eliminated five times more cancer cells than docetaxel on its own without affecting healthy cells. It was especially effective against U87MG, a glioblastoma cell that overexpresses VEGF, but less so against A172, which expresses relatively little VEGF. “These findings show that our nanocarrier selectively attacks cells that express high VEGF,” Di Filippo said.
The researchers also found that the potential drug could enter the cancer cells and release docetaxel continuously for about 84 hours, suggesting a prolonged availability of the chemotherapy drug in the body.
Good results in animals
Using techniques developed by the UNICAMP team, rats were inoculated with glioma cells (glioma is a type of cancer similar to glioblastoma). Five days later they were divided into six groups: placebo treatment; docetaxel sol; nanoportador alone, without bevacizumab or docetaxel; nanocarrier and bevacizumab, without docetaxel; nanocarrier and docetaxel, without bevacizumab; nanoportador with docetaxel and bevacizumab.
After 15 days, it was found that the first four groups had not benefited from the treatment. In the fifth group (nanocarrier with docetaxel) and the sixth group (nanocarrier with docetaxel and bevacizumab), tumor volume was reduced by 40% and 70%, respectively. “These are significant figures for such trials,” Chorilli said.
The researchers also found that the formulation did not cause any deterioration in the levels of biomarkers such as albumin and creatinine compared to the use of docetaxel alone. “This shows that the toxicity did not intensify,” Di Filippo explained.
Next steps
According to Chorilli, the results were positive, but these were the first experiments with the nanostructured lipid transporter for this specific application. “We need to do more studies using cells and isolated animals. If the results against glioblastoma multiforme are still good, we could try to find partners for clinical trials with human volunteers,” he said.
The study reported in the article highlighted the potential of lipid nanocarriers in the treatment of brain cancer, adding: “We can use different combinations with other monoclonal antibodies and chemotherapy drugs against other types of cancer. No doubt, many will be needed. more years to complete this research “.
Chorilli is studying similar methods for treating infections, such as gastritis and other diseases caused by the bacterium Helicobacter pylori, in research also supported by FAPESP.
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