[Theo Ruprecht] Was Ruprecht | FAPESP agency – A carrier that could reach the brain, involved in an invasive type of tumor known as glioblastoma multiforme, and developed chemotherapy drugs, were first tested by Brazilian researchers. The second Article Published in Journal International Journal of Pharmaceuticals Potential treatments using a combination of warm technology, chemotherapy, and a monoclonal antibody showed efficacy in isolated cells and animal models.
Glioblastoma multiforme, in addition to representing 60% of all brain cancers, is also the most invasive type. Even in surgery, radiotherapy and conventional chemotherapy, the average lifespan of a patient is about 14 months. One reason for this is that the tumor causes its blood vessels to grow rapidly – a process called angiogenesis.
“And since it exists in the brain, there is more difficulty: getting drugs to cross the blood-brain barrier. [estrutura que filtra a passagem de substâncias para o sistema nervoso central] And get to him, “he adds. Leonardo Di Filippo Pharmacist-Biochemist at the Bachelor of Pharmaceutical Science program at the Faculty of Pharmaceutical Sciences at the Universidad Estaduel Paulista (UNESP) in Araraquara.
To overcome these challenges, Di Filippo and other researchers from Unesp, the University of Sनाo Paulo at Campinas State University (Unicamp) and Ribeirão Preto (USP) included docetaxel, a powerful chemotherapy drug, a nanostructured lipid carrier – on a lipid basis. Who can cross the blood-brain barrier. “We have developed a formula in which substances combine in a stable way,” de Filippo comments.
Professionals also added Bevacizumab, a monoclonal antibody already approved for other purposes, targeting endothelial growth factor (VEGF) in this carrier. “It is a cancer protein that stimulates angiogenesis and is overexpressed to multiforme in glioblastoma,” de Filippo explains. In other words, the proposal was to create a structure that could enter the brain, specifically targeting the tumor and then releasing chemotherapy drugs to destroy it.
“The development of this system, with this application, is an innovation,” he says Marlus stole He was a professor and project coordinator of UNESP Support From FAPESP.
Quality test
Once a nanostructured lipid carrier was created with docetaxel and bevacizumab, researchers began to verify that it met these basic criteria. In the laboratory, it was found to be 128 nanometers long, large enough to cross the blood-brain barrier.
The product was able to trap 90% of dosatexel and add 62% of bevacizumab to its composition. “These are positive numbers. Within these thresholds, we were able to guarantee adequate therapeutic concentrations,” De Filippo highlights.
The next step was to evaluate the effect of the compound on cell lines and healthy cells in two glioblastomas. Compared to dosatexel alone, the warm carrier killed five times more cancer cells without affecting healthy people.
Of the strains in glioblastoma, the compound was particularly effective against U87MG, which overpresses VEGF. Its effect is lessened in A172, which is lower in this protein. “It is a fact that it strengthens the ability of our warm carriers to selectively attack cells with high expression of proteins,” says Di Filippo.
The researchers also confirmed that the potential drug was able to penetrate the diseased cells and release dosatexel for about 84 hours, suggesting a long-term availability of chemotherapeutics in the body.
Good results in animals
Using techniques developed by the Unicamp team, mice were vaccinated with glioma cells (a type of cancer similar to glioblastoma). Five days later, they were divided into six groups: placebo treatments; Treatment with docetaxel alone; Nano carrier therapy alone without bevacizumab and docetaxel; nanocarrier-based treatment with bevacizumab, but without docetaxel; nanocarrier-based treatment with docetaxel, but without bevacizumab; And nanocarrier-based treatments with docetaxel and bevacizumab.
After 15 days of therapy, it was noted that the first four groups did not benefit from the therapy. Warm carriers with docetaxel led to a 40% reduction in the amount of cancer within the brain. And, when the compound was buoyant, the reduction was 70%. “This is a very important number for this type of work,” he said.
The formula also does not show a poor index of biomarkers such as albumin and creatinine compared to isolated use of docetaxel. “This indicates that the toxicity is not acute,” refers to de Filippo.
Revealed
Chorilli highlights, albeit encouragingly, that these nanostructured lipid carriers are the first experiments in question with this application. “We need to move forward with further studies in isolated cells and animals,” he thinks. “If research continues to show positive results against multiforme in glioblastoma, we may try to find partnerships to conduct clinical trials with volunteers,” he concludes.
The professional adds that this article strengthens the potential of lipid warm-up carriers to fight malignant tumors. “We can use different combinations, other monoclonal and chemotherapeutic antibodies, against other cancerous strains”, Chorilli gives an example. “It’s a line of research that is undoubtedly many years ahead,” he highlighted.
Chorilli, by the way, is studying similar methods against bacterial infections Helicobacter pylori Which causes gastritis. There is also work Support From FAPESP.
Article Targeted delivery of multiforme dosatexel in glioblasto inhibits in vitro cell growth and in vivo tumor progression using bevacizumab-modified nanostructured lipid carriers. Leonardo Dellelo de Filippo, Jonatas Lobato Duarte, Juliana Hofstatter Ajambuja, Marcela Tavares Luiz, Victor Hugo Sausa Araujo, Ingrid Delbon Figueroa, Lucas Bareto-de-Sujael, , Sara Teresinha Ollala Saad and Marlus Chorilli. Text can be accessed at: .