Lipids-coated microbubbles produced via microfluidics for ultrasonic imaging and gene delivery applications

• Grant number: 18/05278-0
• Support type: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): June 01, 2018
• Effective date (End): May 31, 2019
• Field of knowledge: Engineering - Chemical Engineering
• Principal researcher: Lucimara Gaziola de la Torre
• Grantee: Amanda da Costa e Silva de Noronha Pessoa
• Supervisor abroad: Patrick Jean Rene Tabeling
• Home Institution: Faculdade de Engenharia Química (FEQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: ParisTech, France
• Associated to the scholarship: 17/08636-2 - Microfluidics as technological platform for production of nanoparticles, nanoaggregates, and their complexes with genetic material, BP.DR

Abstract

Microbubbles oscillate when driven by an ultrasonic pulse, and this acoustic property make them useful as ultrasound contrast agents for diagnostics imaging. Alternatively, microbubbles can be disrupted by applying a focused ultrasound beam, also providing the possibility of local release of drugs or genes. The use of thin lipid shells to stabilize the microbubbles gas-liquid interface make these applications possible, and offer different possibilities of tailoring the bubbles surface by using targeting ligands for specific tissue attachment and enhanced therapeutic delivery. In this context, microfluidic devices provide further opportunity for tuning the interfacial coverage of individual droplets, and enabling the synthesis of microbubbles with controlled properties. The main goal of this research project is to use a microfluidic device based on hydrodynamic focusing to produce lipid-coated oil droplets and to evaluate freeze-drying as an approach to obtain highly monodisperse microbubbles with long-term storage and stability. Additionally, the microbubbles lipid shell will be functionalized with cyclic peptides based on the sequence arginine, glycine and aspartate (cRGD), which are selective for cell surface receptors of integrins expressed in tumor cells. Finally, we will investigate the microbubbles loading with DNA, mediated by electrostatic interactions with the lipid shell, for synthesis of targeted microbubbles for gene delivery applications. This work will be developed in collaboration with Professor Patrick Tabeling's research group (MMN Lab) from École Supérieure de Physique et Chimie Industrielles (ESPCI Paris). Professor Patrick Tabeling has a renowned expertise in microfluidics, including fundamental investigations of interface dynamics for development of droplets and bubbles for sustained delivery and healthcare applications. (AU)

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)

GORMLEY, CATHERINE A.; KEENAN, BENJAMIN J.; BUCZEK-THOMAS, JO ANN; PESSOA, AMANDA C. S. N.; XU, JIANG; MONTI, FABRICE; TABELING, PATRICK; HOLT, R. GLYNN; NAGY, JON O.; WONG, JOYCE Y. Fibrin-Targeted Polymerized Shell Microbubbles as Potential Theranostic Agents for Surgical Adhesions. Langmuir, v. 35, n. 31, SI, p. 10061-10067, AUG 6 2019. Web of Science Citations: 1.