Development of functionalized liposome with cyclic RGD peptide in microfluidic device for site: specific gene delivery

• Grant number: 16/10337-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2016
• Effective date (End): July 31, 2017
• Field of knowledge: Engineering - Chemical Engineering
• Principal Investigator: Lucimara Gaziola de la Torre
• Grantee: Gabriel Perli
• Host Institution: Faculdade de Engenharia Química (FEQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Drug delivery systems are rapidly gaining importance in pharmaceutical research and development, due to the offering of controlled delivery of biologically active agents, representing a promising strategy for the treatment of many kinds of cancer. This strategy is based on the chemical modification of the nanocarriers surfaces with linker groups to which tumor cell receptors have high selectivity and specificity. These nanocarriers are designed and developed to increase the biopharmaceuticals retention in the targeted cells and minimize the damage to healthy cells. The functionalization of liposomes with cyclic RGD peptide (cRGD) is a possible method to enhance the nanocarriers internalization in the cancerous cells by receptor-mediated endocytic mechanisms. These peptides are able to interact specifically with cell receptors usually expressed in tumor cells. However, for the clinical application of these drug delivery systems, effective methods to manufacture liposomes decorated with cRGD are necessary. In this context, Microfluidics appear as a promising technology for the production of liposomes with suitable physicochemical properties for biological applications, overcoming some obstacles encountered in conventional processes. Thus, the main goal of this research project is developing liposomes decorated with cRGD peptides in a microfluidic device. For project execution the following steps are crucial: (I) obtaining phospholipids chemically modified with cyclic RGD peptide to (II) production of decorated liposomes in a microfluidic system, to increase the biorecognition of nonviral gene nanocarriers by the targeted cells. For this purpose, two strategies to produce the decorated liposomes with cRGD peptide will be applied: introducing derivatized lipid with the others lipids (EPC/DOTAP/DOPE/DSPE-PEG) in the inlet of the microfluidic device and inserting the derivatized lipid after the liposomes formation (post insertion). The synthesis of phospholipids chemically modified with cyclic RGD peptide will be carried out in collaboration with the Institute of Chemistry, UNICAMP, with Professor Ronaldo A. Pilli's group. Therefore, with this project, we expect to improve the gene delivery of nonviral lipid carriers and to develop innovative processes for their synthesis, contributing to the progress in gene delivery and vaccine areas.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PERLI, GABRIEL; PESSOA, AMANDA C. S. N.; BALBINO, TIAGO A.; DE LA TORRE, LUCIMARA G.. Ionic strength for tailoring the synthesis of monomodal stealth cationic liposomes in microfluidic devices. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 179, p. 233-241, JUL 1 2019. (17/08636-2, 16/10337-0)