For the first time, Brazilian researchers have tested a drug carrier that can reach the brain, bind to an aggressive type of tumor called glioblastoma polymorphism, and release chemotherapeutic agents.
According to the article published in International Journal of PharmaceuticsPotential therapies have been shown to be effective in isolated cell and animal models, thanks to a combination of nanotechnology, chemotherapy, and monoclonal antibodies.
Glioblastoma polymorphic glioblastoma accounts for 60% of all brain tumors in adults and is also the most aggressive type of brain tumor. Even after surgery, radiation therapy, and conventional chemotherapy, patients live on average about 14 months. One of the reasons is angiogenesis. This is the process of quickly creating unique blood vessels for a tumor to develop.
Another issue is the blood-brain barrier. This prevents the drug from reaching the tumor... “
Leonardo DiCappo, Ph.D. Researcher, Faculty of Pharmacy, State University of Sao Paulo, Araraquara
To address these challenges, Di Filippo is working with researchers at UNESP and two other Brazilian institutions, the University of Campiners (UNICAMP) and the University of São Paulo (USP), Ribey Lampreto, for intensive chemotherapy. A nanostructured lipid carrier designed to cross the blood-brain barrier through the drug docetaxel. “We have developed a product that is a stable combination of substances,” he said.
Researchers also bound the carrier to bevacizumab, a monoclonal antibody developed against it. Vascular Endothelial Growth Factor Approved for (VEGF) and other uses. “VEGF is a cancer protein that stimulates angiogenesis and tends to be overexpressed in glioblastoma polymorphism,” DiFilippo explained. The goal was to create a formulation that could penetrate the brain and release chemotherapeutic agents to destroy the tumor.
“Developing this system using this application is an innovation,” said Marlus Chorili, a professor at UNESP and a principal investigator for a project supported by FAPESP.
Quality test
After creating a nanostructured lipid carrier using docetaxel and bevacizumab, researchers set out to ensure that it meets certain basic criteria. Laboratory tests have shown that its size is 128 nanometers, small enough to overcome the blood-brain barrier. In addition, docetaxel capture was 90% and bevacizumab coupling efficiency was 62%. “These are positive numbers, enough to guarantee the right therapeutic concentration,” said Diffilippo.
The next step was to assess the effect of the compound on two glioblastoma cell lines and healthy cells. NanoCarrier has eliminated five times as many cancer cells as docetaxel by itself without affecting healthy cells. This was particularly effective against U87MG, a glioblastoma cell that overexpresses VEGF, but less so against A172, which expresses relatively low amounts of VEGF. “These findings show that our nanocarriers selectively attack cells that express many VEGFs,” said DiFilippo.
Researchers have also found that potential drugs can enter cancer cells and release docetaxel continuously for about 84 hours. This suggests the long-term availability of chemotherapeutic agents in living organisms.
Good results with animals
Rats were inoculated with glioma cells using a technique developed by the UNICAMP team (glioma is a type of cancer that resembles glioblastoma). Five days later, they were divided into six groups. Docetaxel alone; bevacizumab or docetaxel-free nanocarriers only. No nanocarriers and bevacizumab, docetaxel. Nanocarriers and docetaxel that do not contain bevacizumab. Nanocarriers containing docetaxel and bevacizumab.
Fifteen days later, it was found that the first four groups did not benefit from treatment. In the fifth group (nanocarriers containing docetaxel) and the sixth group (nanocarriers containing docetaxel and bevacizumab), tumor volume was reduced by 40% and 70%, respectively. “These are significant figures for this type of test,” says Chollilli.
The researchers also found that the formulation did not reduce the levels of biomarkers such as albumin and creatinine compared to when docetaxel was used alone. “This indicates that the toxicity was not enhanced,” explained Diffilippo.
Next step
According to Chorilli, the results were positive, but these were the first experiments using nanostructured lipid carriers for this particular application. “We need to do more research with isolated cells and animals. If the results for glioblastoma polymorphism remain good, we can find a partner for clinical trials by human volunteers,” he said. Said.
The study reported in the article highlights the potential of lipid nanocarriers in the treatment of brain tumors and “can be used in various combinations with other monoclonal antibodies and chemotherapeutic agents against other types of cancer. It will definitely take years to complete. “
Chorilli is researching similar methods for the treatment of infections such as gastritis and other diseases caused by bacteria. Helicobacter pyloriAlso supported by FAPESP in research.
sauce:
Fundação de Amparoà Pesquisado Estado de São Paulo
Journal reference:
Diffilippo, L, D. , et al.. (2022) Targeted delivery of docetaxel polyglioblastoma using a bevacizumab-modified nanostructured lipid carrier is impaired In vitro Cell proliferation and in vivo tumor progression. International Journal of Pharmaceutics.. doi.org/10.1016/j.ijpharm.2022.121682