In vitro biocompatibility and anti-glioblastoma activity of functionalized liposomes loaded with temozolomide under dynamic conditions

• Grant number: 23/15267-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: May 01, 2024
• End date: April 25, 2025
• Field of knowledge: Engineering - Biomedical Engineering - Bioengineering
• Principal Investigator: Marlus Chorilli
• Grantee: Jessyca Aparecida Paes Dutra
• Supervisor: Gianni Ciofani
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Itt Center For Materials Interfaces, Italy
• Associated to the scholarship: 21/02609-9 - Evaluation of the potential of transferrin functionalized liposomes dispersed in mucoadhesive hydrogels for nasal delivery of temozolomide in the treatment of glioblastoma multiform., BP.DR

Abstract

Glioblastoma Multiforme (GBM) is the most aggressive and prevalent variation of glioma. Temozolomide (TMZ), the standard treatment, is a prodrug that hydrolyzes at physiological pH (> 7.0) to form ion responsible for DNA alkylation. The limited therapeutic efficacy and low survival required alternatives to overcome the therapeutic drawbacks associated with properties of TMZ and the physiological barriers such as the blood-brain barrier (BBB). For this, targeted administration using nanosystems has been widely explored and is proving to be a potential strategy for the treatment of GBM. Although nanotechnology is a promising approach, its translation to the clinic is limited by the lack of cellular models that may provide reliable and predictive knowledge about the pre-clinical in vivo efficiency of the formulation. Fluidic systems are promising tools for studying the efficacy and safety of nanosystems under development. The aim of this project is to study the evaluate the biocompatibility and anti-glioblastoma activity of functionalized liposomes loaded with temozolomide using in vitro analyses under dynamic conditions. A biomimetic model of the blood-brain barrier made by Two-Photon Lithography (TPL), patented by Ph.D. Gianni's group, will be used as the basis for developing a Nose Brain Barrier in vitro model. The aim will be to mimic transnasal administration using a fluidic system. The liposomes activity is evaluated by perfusing the nanoparticles through the device using a peristaltic pump, thus recreating a simplified model of microenvironment. The research will be carried out at the Istituto Italiano di Tecnologia (Pontedera, Italy) under the supervision of Prof. Gianni Ciofani, Ph.D. This study will contribute to understanding the influence of dynamic conditions on the accumulation, vectorization and consequently the efficacy of liposomes containing TMZ in the tumor microenvironment, as well as biocompatibility in basal cells.