Microfluidics as technological platform for production of lipid micro- and nanocarriers for nanomedicine applications

Author(s)

Amanda da Costa e Silva de Noronha Pessoa

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Engenharia Química
• Defense date: 2020-04-07

Examining board members

Lucimara Gaziola de la Torre; Rosiane Lopes da Cunha; Sang Won Han; Adriano Rodrigues Azzoni; Mário Ricardo Gongora Rubio

• Advisor: Lucimara Gaziola de la Torre

Abstract

Non-viral carriers, especially lipid-based ones, have been used as sustained drug and gene delivery systems for the treatment of diseases in the fields of drug and gene therapy. Among the production methods, microfluidic platforms allow the synthesis of nanoparticulate systems with uniform properties in reproducible processes. In this context, this work aimed at developing microfluidic processes for production of lipid-based micro and nanocarriers, regarding cationic liposomes functionalized with poly(ethylene glycol) (PEG) (stealth) and lipid-coated microbubbles. In the first phase of this project, through microfluidic devices based on hydrodynamic focusing, we discovered that the increase in ionic strength leads to the modulation of lipid self-assembly mechanism, preventing micelle formation and promoting the synthesis of monodisperse stealth cationic liposomes (SCL) (with 1% of DSPE-PEG2000 lipid). High ionic strength conditions resulted in SCL with mean diameter of 140 nm and polydispersity index (PDI) lower than 0.2. The SCL were further characterized by small-angle X-ray scattering (SAXS) and transmission electron cryomicroscopy (cryo-TEM) techniques, indicating the formation of multilamellar SCL concomitantly to the increase in ionic strength. Finally, we studied the complexation of these lipid nanocarriers with genetic material (plasmidial DNA) and we assessed their gene delivery ability in terms of transfection efficiency in prostate cancer cells (PC3) and normal prostate epithelium cells (PNT2). In the second stage of this project, different microfluidic devices were studied for the formation of monodisperse lipid-stabilized microbubbles. We investigated the influence of process parameters for the optimization of monodisperse microbubbles production, aiming at future applications as ultrasound contrast agents and as gene delivery vectors. Thus, this study contributed to the phenomenological understanding and to the development of microfluidic processes for synthesis of lipid carriers. This technology stands out as a promising tool for different applications in the field of nanomedicine (AU)

• FAPESP's process: 17/08636-2 - Microfluidics as technological platform for production of nanoparticles, nanoaggregates, and their complexes with genetic material
• Grantee: Amanda da Costa e Silva de Noronha Pessoa
• Support Opportunities: Scholarships in Brazil - Doctorate