Microfluidic Production of Lysolipid-Containing Temperature-Sensitive Liposomes

J Vis Exp. 2020 Mar 3:(157). doi: 10.3791/60907.

Abstract

The presented protocol enables a high-throughput continuous preparation of low temperature-sensitive liposomes (LTSLs), which are capable of loading chemotherapeutic drugs, such as doxorubicin (DOX). To achieve this, an ethanolic lipid mixture and ammonium sulfate solution are injected into a staggered herringbone micromixer (SHM) microfluidic device. The solutions are rapidly mixed by the SHM, providing a homogeneous solvent environment for liposomes self-assembly. Collected liposomes are first annealed, then dialyzed to remove residual ethanol. An ammonium sulfate pH-gradient is established through buffer exchange of the external solution by using size exclusion chromatography. DOX is then remotely loaded into the liposomes with high encapsulation efficiency (> 80%). The liposomes obtained are homogenous in size with Z-average diameter of 100 nm. They are capable of temperature-triggered burst release of encapsulated DOX in the presence of mild hyperthermia (42 °C). Indocyanine green (ICG) can also be co-loaded into the liposomes for near-infrared laser-triggered DOX release. The microfluidic approach ensures high-throughput, reproducible and scalable preparation of LTSLs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Ammonium Sulfate
  • Buffers
  • Chemistry, Pharmaceutical / methods*
  • Chromatography
  • Doxorubicin / administration & dosage*
  • Drug Delivery Systems*
  • Hydrogen-Ion Concentration
  • Indocyanine Green / administration & dosage*
  • Lab-On-A-Chip Devices
  • Lipids / chemistry*
  • Liposomes / chemistry*
  • Microfluidics*
  • Temperature

Substances

  • Buffers
  • Lipids
  • Liposomes
  • Doxorubicin
  • Indocyanine Green
  • Ammonium Sulfate