In vitro cytotoxicity of lipid nanoparticles functionalized with cannabinoid compounds for encapsulation of the chemotherapy drug paclitaxel

• Grant number: 25/01405-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Eneida de Paula
• Grantee: Rayza Catheryne Pereira da Costa
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 24/02479-6 - Lipid-based nanocarriers in antineoplastic chemotherapy: from experimental design and functionalization to in vivo testing, with the goal of enhancing efficacy and reducing the toxicity of breast cancer treatment, AP.R

Abstract

Breast cancer is a major public health problem because it is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths in women worldwide. In Brazil, excluding non-melanoma skin tumors, breast cancer (BC) is the most common cancer in women of all regions and, despite advances in therapy, chemotherapy based on taxanes and anthracyclines still represents the mainstay of clinical treatment. Paclitaxel (PTX) is a broad-spectrum chemotherapeutic agent of the taxane class used to treat different subtypes of BC; it has low bioavailability and its commercial formulation contains solubilizing agents (surfactant and alcohol) which increase its systemic toxicity. Nanostructured lipid carriers (NLC) are drug delivery systems (DDS) stabilized by surfactant and whose interior is formed by a mixture of solid and liquid lipids, which increase the time of action and reduce the toxicity of liposoluble active ingredients. NLCs can be prepared with functional excipients that give the nanoparticles pharmaceutical properties as well as a structural effect. The phytocannabinoid cannabigerol (CBG) has anti-inflammatory, antioxidant and anticancer properties. Although less studied than other cannabinoids, its medicinal use has also aroused interest for its anti-tumor properties. However, CBG has low aqueous solubility and is vulnerable to degradation by auto-oxidation, light and temperature. Therefore, in this project, our strategy is to increase the bioavailability of both active ingredients (PTX and CBG) by incorporating them into lipid nanoparticles. In a previous project (PIBITI/CNPq 2023-2024), the student developed a formulation containing PTX and functionalized with cannabidiol that showed promising results, with greater cytotoxicity against 4T1 tumor cells than commercial PTX (IC50 values = 0.34 µM and 1.1 µM - p < 0.001- respectively). In view of this, we intend to verify the antineoplastic effect of a new formulation, to be developed with PTX and containing cannabigerol as a liquid lipid.