DEVELOPMENT AND PHYSICAL-CHEMICAL CHARACTERIZATION OF NANOSTRUCTURED LIPID CARRIERS FUNCTIONALIZED WITH CANNABIDIOL FOR TARGETED DELIVERY OF TEMOZOLOMIDE

• Grant number: 24/16763-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Jonatas Lobato Duarte
• Grantee: Leticia Andrade Nascimento
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Glioblastoma Multiforme (GBM) is the most aggressive malignant brain tumor of the Central Nervous System (CNS). Conventional treatments, such as surgery, radiotherapy and chemotherapy with temozolomide (TMZ), have limitations due to the characteristics of tumor invasiveness, resistance to radiotherapy and difficulty of drugs in crossing the blood-brain barrier (BHE). Nanotechnology stands out for enabling alternatives, such as the use of nanoparticles for drug delivery. Nanostructured lipid carriers (CLNs) have proven promising for the delivery of chemotherapeutic drugs to the CNS, overcoming the limitations of BHE and consequently improving the delivery of anti-GBM agents. In addition, cannabidiol (CBD), a non-psychoactive compound of Cannabis sativa L., has antitumor properties, in addition to other activities such as sensitizing neoplastic cells to radio and chemotherapy, in addition to acting as an active directing agent where endocannabinoid receptors are expressed, as in the case of GBM. Thus, the objective of this work is to develop a nanostructured lipid carrier, coated with cannabidiol and containing encapsulated TMZ for the targeted and selective delivery of the drug. The CLNs will be obtained by the emulsification method followed by sonication, and will be characterized physico-chemically in terms of their size, polysidispersivity index, zeta potential, encapsulation efficiency, functionalization efficiency, in vitro release profile and morphology, as well as their thermal behavior by differential exploratory calorimetry analysis. Finally, the CLNs functionalized with CBD containing TMZ (CBD-CLN-TMZ) will have their biological properties investigated in U87MG cells (human glioma), C6 (rat glioma) and L929 (healthy mouse fiblobasts), regarding their cytotoxicity and cellular internalization.