Microfluidic systems for the formation of liposomal nanostructures for gene carrier

Author(s)

Tiago Albertini Balbino

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Engenharia Química
• Defense date: 2016-02-29

Examining board members

Lucimara Gaziola de la Torre; Eneida de Paula; Rosiane Lopes da Cunha; Antonio Augusto Malfatti Gasperini; Adriano Rodrigues Azzoni

• Advisor: Lucimara Gaziola de la Torre

Abstract

Microfluidics allows the formation of a variety of nanoparticles and nanocarriers systems via controlled mixing of streams that flow within micro-sized channels. Cationic liposomes have been employed as an efficient alternative for the delivery of genetic material and therapeutic drugs for biomedical applications. The use of microfluidic processes for the formation of liposomes and their complexes with DNA (lipoplexes) enables the reduction of the number of steps compared to conventional processes, allowing the development of processes liable to scale amplification. The present work aimed at the development of continuous-flow microfluidic platforms to generate nonviral vectors based on cationic liposomes and plasmid DNA (pDNA) and their applications in gene therapy. Firstly, a microfluidic device based on the hydrodynamic flow-focusing technique was employed to form electrostatic complexes between pDNA and liposomes for the formation of lipoplexes. Under high pDNA loading conditions, physicochemical and structural properties of lipoplexes obtained in the microfluidic process resulted in more efficient biological assays than those obtained via conventional bulk process. Next, flow-focusing regions were associated in series and pseudo-parallel architectures for the formation of liposomes with higher productivity per device. In both architectures, it was possible to obtain liposomes with a protective and steric shield provided by poly(ethylene glycol) (PEG), whose properties were appropriate for gene therapy applications. Lastly, using consecutives flow-focusing regions, a microfluidic device was developed with two distinct regions for the formation of liposomes and lipoplexes with significantly reduced number of steps, contributing to the advances of gene nanocarriers for biomedical applications (AU)

• FAPESP's process: 12/23143-9 - Microfluidic systems for production of multifunctional nanoparticles for gene and vaccine therapy
• Grantee: Tiago Albertini Balbino
• Support Opportunities: Scholarships in Brazil - Doctorate