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In vivo evaluation of the antitumor effect of bupivacaine S75: R25 encapsulated in nanostructured lipid carriers functionalized in melanoma

Grant number: 21/02575-7
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): March 01, 2022
Effective date (End): February 28, 2023
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Eneida de Paula
Grantee:Gabriela Geronimo
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


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).

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
GERONIMO, Gabriela. Pharmacokinetic and pharmacodynamic evaluation of the treatment of murine melanoma with lavand-oil nanostructured lipid carriers containing S75:R25 bupivacaine. 2023. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.

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