This project aims at the technological development of microfluidic process for nonviral carriers production based on the electrostatic complexation among cationic liposomes (CL), peptides with nuclear localization signals (NLS) and plasmid DNA (pDNA) for gene and vaccine therapy applications. Microfluidics uses devices that manipulate small amounts of fluids and allow the electrostatic complexation in continuous mode, with the diffusion conditions control, which also allows better size control of the obtained complexes. Methodologically, the present project will be carried out in four main steps: firstly, the electrostatic complexation process between NLS and pDNA in microfluidic devices will be studied, with the conventional bulk complexation process as comparison. The physicochemical and biological properties of the complexes obtained by the microfluidic devices will be investigated in order to elucidate the process formation of these complexes. The second part of this work will explore the formation of the pDNA/LC complexes in different microfluidic devices based on the hydrodynamic focusing technique in only one step, with the simultaneous formation of the CL and its complexation with pDNA. This part will be a continuity of the research that has already been started during the master dissertation of the doctoral student of this project. The third step, in a collaboration project with the "Biochemical Science Division" of the "National Institute of Standards and Technology" (NIST) in Gaithersburg/Maryland, United States, the formation of CL will be explored in microfluidic devices of different geometries, based on the previous knowledge of each research group. Finally, in the forth step, it will be carried out the development of microfluidic devices for the formation of pseudo-ternary complexes composed of pDNA, LC and NLS, to obtain multifunctional complexes for gene and vaccine therapy. This project will contribute to the development of new microfluidic processes and of pharmaceutical products for gene and vaccine therapy.
News published in Agência FAPESP Newsletter about the scholarship: