Viscous Core Liposomes Increase siRNA Encapsulation and Provides Gene Inhibition When Slightly Positively Charged

Shayan Ahmed; Hugo Salmon; Nicholas Distasio; Hai Doan Do; Daniel Scherman; Khair Alhareth; Maryam Tabrizian; Nathalie Mignet

doi:10.3390/pharmaceutics13040479

Viscous Core Liposomes Increase siRNA Encapsulation and Provides Gene Inhibition When Slightly Positively Charged

Pharmaceutics. 2021 Apr 1;13(4):479. doi: 10.3390/pharmaceutics13040479.

Authors

Shayan Ahmed¹, Hugo Salmon², Nicholas Distasio², Hai Doan Do¹, Daniel Scherman¹, Khair Alhareth¹, Maryam Tabrizian², Nathalie Mignet¹

Affiliations

¹ Unité des Technologies Chimiques et Biologiques Pour la Santé (UTCBS), CNRS, INSERM, Université de Paris, F-75006 Paris, France.
² Biomedical Engineering Department and Faculty of Dentistry, McGill University, 3775 University St, Montreal, QC H3A 2B4, Canada.

Abstract

Since its discovery, evidence that siRNA was able to act as an RNA interference effector, led to its acceptation as a novel medicine. The siRNA approach is very effective, due to its catalytic mechanism, but still the limitations of its cellular delivery should be addressed. One promising form of non-viral gene delivery system is liposomes. The variable and versatile nature of the lipids keeps the possibility to upgrade the liposomal structure, which makes them suitable for encapsulation and delivery of drugs. However, to avoid the limitation of fast release for the hydrophilic drug, we previously designed viscous core liposomes. We aimed in this work to evaluate if these viscous core liposomes (NvcLs) could be of interest for siRNA encapsulation. Then, we sought to add a limited amount of positive charges to provide cell interaction and transfection. Cationic lipid dimyristoylaminopropylaminopropyl or the polymer poly(ethylenimine) were incorporated in NvcL to produce positively charged viscous core liposomes (PvcL) by a customized microfluidic device. We found that NvcLs increased the encapsulation efficiency and loading content with regards to the neutral liposome. Both PvcL_PEI and PvcL_DMAPAP exhibited transfection and GFP knock-down (≈40%) in both 2D and 3D cell cultures. Finally, the addition of slight positive charges did not induce cell toxicity.

Keywords: 3D cell cultures; dimyristoylaminopropylaminopropyl; encapsulation efficiency; gene delivery; loading content; microfluidic device; neutral viscous core liposomes; poly(ethylenimine); positively charged viscous core liposomes; siRNA.