Of the malignant tumors registered in Brazil, skin cancer is the most frequent and corresponds to about 30% of the cases. Melanoma is a type of skin cancer that, despite its low incidence (3% of malignant neoplasms), is the most aggressive form of skin cancer given its high metastatic potential (mainly brain), high mortality (80%) and resistance to therapy with chemotherapeutic agents. Therefore, new ways to treat melanoma have been the subject of research. Bupivacaine is a potent local anesthetic with a long-lasting effect, widely used in surgical procedures; marketed in the form with levorotatory enantiomeric excess (BVCS75), with less systemic toxicity. Recent studies have shown that bupivacaine has an antineoplastic effect, causing changes in cellular bioenergetics and inducing apoptosis. However, for a bupivacaine to be used as an antineoplastic agent, it is necessary to circumvent limitations imposed by its small therapeutic window, avoiding adverse effects to SCV / CNS. Thus, carrying out to extend the action time of bupivacaine (beyond 4 hours) without increasing its systemic toxicity allows the repositioning of this drug. Nanostructured lipid carriers (CLN) are sustained release systems (Drug-Delivery Systems) prepared from a mixture of solid and liquid lipids, plus surfactant. These lipids can act as excipients from pharmaceutical properties in addition to CLN. This project aims to test the treatment of melanoma from a base of BVCS75 encapsulated in CLN (previously optimized by factorial design) that have lavender essential oil as a functional excipient. For this purpose, in vitro assays (in murine (B16F10) and human (SK-MEL-103) melanoma tumor cell lines) will be performed for cytotoxicity analysis, cell death profile, proliferation (clonogenic assay) and cell migration (healing assay) of wounds), and in vivo assays (in a model of melanoma induced in Mus musculus mice), with hematological, biochemical, histomorphological analysis and tumor volume evaluation comparing the potential for tumor growth inhibition with monotherapy with the conventional antineoplastic agent dacarbazine (DBZ).
News published in Agência FAPESP Newsletter about the scholarship: