Ionic strength for tailoring the synthesis of monomodal stealth cationic liposomes in microfluidic devices

Author(s)

Perli, Gabriel ^[1] ; Pessoa, Amanda C. S. N. ^[2] ; Balbino, Tiago A. ^[3] ; de la Torre, Lucimara G. ^[2]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Inst Chem, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Sch Chem Engn, POB 6066, BR-13086090 Campinas, SP - Brazil

^[3] Univ Fed Rio de Janeiro, UFRJ COPPE, Nanotechnol Engn Program, BR-21941972 Rio De Janeiro, RJ - Brazil

• Document type: Journal article
• Source: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 179, p. 233-241, JUL 1 2019.
• Web of Science Citations: 0

Abstract

In this work, we describe a hydrodynamic flow-focusing microfluidic process to produce stealth cationic liposomes (SCL), stabilized with poly(ethylene glycol) (PEG), with uniform and reproducible features. Through cryogenic transmission electron microscopy (cryo-TEM) characterization and real-time monitoring, we verified the formation of multi-sized lipid self-aggregates, which can be attributed to micelles formation. These structures tend to undergo deposition within the PDMS/glass microchannels through intermolecular interactions with the glass walls, hindering not only the process reproducibility but also the final biological application of the SCL products. In view of this, we propose the modulation of ionic strength of the side streams aiming to ionically shield the glass surface, decrease the intermolecular interactions of the lipid polar heads, and, essentially, to promote the bilayer-driven self-assembly of SCL with 1% of DSPE-PEG2000 lipid. Herein, we applied phosphate buffered saline (PBS) from 10 to 50 mM concentration as side streams, and evaluated its effects on SCL final physicochemical properties in terms of size distribution, mean diameter, zeta potential and polydispersity index (PDI). We present evidences indicating that the ionic strength can be used as a microfluidic process parameter to modulate the lipids self-assembly kinetics whilst preventing micelles formation. Finally, the proposed diffusion based microfluidic system with high ionic strength enables the formation of monodisperse (PDI < 0.2) SCL of around 140 nm with monomodal size distributions and enhanced properties when compared to usual bulk mixing. (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
• FAPESP's process: 16/10337-0 - Development of functionalized liposome with cyclic RGD peptide in microfluidic device for site: specific gene delivery
• Grantee: Gabriel Perli
• Support Opportunities: Scholarships in Brazil - Scientific Initiation