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Hydrodynamic Flow-Focusing microfluidic systems for cationic liposome production

Grant number: 13/14925-6
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): October 01, 2013
Effective date (End): September 30, 2014
Field of knowledge:Engineering - Chemical Engineering - Chemical Process Industries
Principal researcher:Lucimara Gaziola de la Torre
Grantee:Tiago Albertini Balbino
Supervisor abroad: Wyatt N. Vreeland
Home Institution: Faculdade de Engenharia Química (FEQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: National Institute of Standards and Technology (NIST), United States  
Associated to the scholarship:12/23143-9 - Microfluidic systems for production of multifunctional nanoparticles for gene and vaccine therapy, BP.DR


Liposomes are amphiphilic lipid systems that, in aqueous media, self-assemble into spherical bilayers with an aqueous interior lumen. The use of cationic lipids allows the electrostatic complexation with DNA, which can then be efficiently delivered to the cell nucleus. This feature makes cationic liposomes (CL) a promising strategy for medical and pharmaceutical applications in the fields of vaccine and gene therapy. Although, the majority of the current techniques used for liposome production are inefficient and require a unit operation step for the size reduction and homogenization of the particles. The use of microfluidic systems in CL production might overcome these major challenges. In this context, this research project, coupled to the candidate's thesis research project, aim the technological development of microfluidic devices for CL production in continuous mode. More specifically, multiple hydrodynamic flow-focusing regions will be associated in parallel and series in order to increase the productivity through the increase in the lipid concentration of the liposomal formulation obtained. The project has the collaboration of National Institute of Standards and Technology, United States. Methodologically, we will carry out the development of the microfluidic devices in two main steps: by associating in parallel and in series one up to three hydrodynamic flow-focusing regions. For each geometry to be studied, we will evaluate the process parameters: volumetric flow rate ratio between aqueous and organic (lipids dispersed in ethanol) streams, total volumetric flow rate and lipid concentration in the organic stream. We will consider as the most appropriate devices the ones that produce CL with the low particle size and polydispersity values. The particle size characterization will be carried out using the equipment Asymmetric Flow Field-Flow Fractionation coupled to multiangle laser light scattering detector. Through this project, one waits to contribute to the development of novel process for one-step liposome production, using microfluidic devices that operate in continuous mode, for gene delivery and vaccine therapy applications. (AU)

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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)
BALBINO, TIAGO A.; SERAFIN, JULIANA M.; RADAIC, ALLAN; DE JESUS, MARCELO B.; DE LA TORRE, LUCIMARA G. Integrated microfluidic devices for the synthesis of nanoscale liposomes and lipoplexes. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 152, p. 406-413, APR 1 2017. Web of Science Citations: 10.

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