Microfluidic synthesis of multifunctional liposomes for targeted drug delivery

Introduction: Multifunctional liposome is a promising nano-system for various applications, such as cancer drug delivery, vaccine delivery, etc. However, more functionality requires more complex synthesis processes, resulting... [ view full abstract ]

Introduction:

Multifunctional liposome is a promising nano-system for various applications, such as cancer drug delivery, vaccine delivery, etc. However, more functionality requires more complex synthesis processes, resulting in poor reproducibility, low yield, and high production cost, hence difficulties in clinical translation. Therefore, it is imperative to develop simple approaches for making multifunctional liposomes.

Methods:

A hydrodynamic flow-focusing (HFF) microfluidic method has been developed to make a library of multifunctional liposomes with systematically varied properties, including PEGylated liposomes (PEG-Lip); single ligand folic acid (FA) modified liposomes (FA-Lip); single ligand cell penetrating peptide TAT modified liposomes (TAT-Lip) and dual-ligand liposomes (FA-TAT-Lip).

Results:

The size of the liposomes with different formulations can be precisely controlled by tuning the microfluidic operation conditions (device design, flow rate ratio, etc) ranging from as low as 50 nm to about 200 nm. The FA-targeted liposomes demonstrated enhanced cellular uptake by the receptor positive cells, but limited tumour penetration capability. While combining the targeting ligand FA and the TAT peptide showed a synergistic targeting and tumour penetration effect.

Discussion:

The microfluidic HFF approach represents a new and very effective way in synthesizing multifunctional liposomes with controllable size and surface properties and superior biological functions, and it will serve as a promising platform for producing multifunctional liposomes for practical applications.