Synthesis of peptide-based nanoparticles on electrostatic complexation via microfluidic route

Resumo

The objective of this project was to condense the naked DNA, of an anionic nature, through electrostatic interactions by cationic polypeptides, resulting in posetively charged complexes and facilitating its introduction through the anionic cell membrane with interest in gene therapy. Polylysine (PLL) demonstrates great potential in this field due to its strongly cationic structure. In order to overcome the toxicity of PLL, an alternative is to complexate it with anionic peptides, such as polyglutamic acid (PGA), aiming to shield its positive charge for further electrostatic condensation with the DNA, allowing cellular transfection. Although there are studies reporting the production of PLL/DNA complexes by conventional bulk synthesis, the microfluidics technology allows greater control over the final characteristics of the nanoparticles produced by favoring the diffusion between the molecules on the flow in laminar regime. Thus, this research project aimed to synthesize PLL/DNA, PLL/PGA polypeptides and the PLL/PGA/DNA ternary complex in both bulk and microfluidic systems, in order to better understand the electrostatic complexation process for future applications in gene therapy. In view of this, the project seeks to add knowledge in the development of new products and processes applied to the areas of nanomedicine and nanotechnology.