Advanced search
Start date
Betweenand

In vitro anti-tumor efficacy of bevacizumab-functionalized nanostructured lipid carrier containing docetaxel for the treatment of glioblastoma multiforme

Grant number: 19/26225-5
Support type:Scholarships abroad - Research Internship - Master's degree
Effective date (Start): September 30, 2020
Effective date (End): March 29, 2021
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Marlus Chorilli
Grantee:Leonardo Delello Di Filippo
Supervisor abroad: Jagdish Singh
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Local de pesquisa : North Dakota State University (NDSU), United States  
Associated to the scholarship:18/18488-3 - Potential evaluation of nanostructured lipid carriers functionalized with bevacizumab to delivery docetaxel in the treatment of glioblastoma, BP.MS

Abstract

Glioblastoma multiforme (GBM) is the most common primary malignant central nervous system cancer, responsible for about 4% of deaths associated with neoplasia, characterized as one of the most fatal human cancers. Chemotherapy is widely present in the treatment of glioblastoma and, among the commercial available drugs, docetaxel (DTX), Taxotere®, is a chemotherapy that has demonstrated efficiency in the treatment of GBM, inhibiting cell pro-liferation due to mitotic block, preventing the depolymerization of microtubules, making them unstable and unfunctional, so that the cell is not able to divide and dies by apoptosis. However, Taxotere® has side effects associated with systemic toxicity from the formula com-pounds or docetaxel itself, as well as limited bioavailability, which limits its clinical use. In order to overcome the blood brain barrier (BHE) and make the drug available more efficiently, a very attractive approach is encapsulation in nanostructured lipid carriers (CLN), which can be functionalized with specific receptor-ligands present in tumor cell surfaces, such as VEGF (vascular endothelium growth factor) receptors, that frequently are super expressed in GBM tumor cells. CLN has a promising application on chemotherapy because it improves the bioa-vailability of drugs poor-soluble drugs such as docexatel, and can selectively deliver it to can-cer cells by the process of functionalization, reducing systemic toxicity and increasing the efficacy of the overall treatment. The current project aims to evaluate the in vitro and in vivo anti-tumor efficacy of bevacizumab-functionalized nanostructured lipid carrier containing docetaxel for the treatment of glioblastoma multiforme. CLNs will be obtained by microemul-sion technique followed by ultrasonication. CLNs functionalization will be promoted by bevacizumab thiolation reaction, and the final formulation (CLN-BVZ) will be characterized regarding their mean size, zeta potential, PDI, encapsulation efficiency, functionalization effi-ciency and morphology. CLN-BVZ will be submitted to in vitro assays in order to determine its cytotoxicity via MTT assay and cellular uptake. The anti-tumor efficacy will be evaluated using 3D in vitro model. Therefore, we ex-pected to obtain an innovative, target-specific CLN that allows selectively deliver docetaxel in therapeutic quantities, as an alternative to the actual pharmacological treatment of GBM.